Journal articles: 'Follicular atresia'

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Migliaccio, M., T. Chioccarelli, C. Ambrosino, A. Suglia, F. Manfrevola, O. Carnevali, S. Fasano, R. Pierantoni, and G. Cobellis. "Characterization of Follicular Atresia Responsive to BPA in Zebrafish by Morphometric Analysis of Follicular Stage Progression." International Journal of Endocrinology 2018 (December 23, 2018): 1–10. http://dx.doi.org/10.1155/2018/4298195.

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Bisphenol A is an industrial chemical compound, pervasively polluting the environment and diet, classified as an endocrine disruptor because of its interference effects on the endocrine system. In zebrafish, BPA exposure induces follicular atresia. To acquire knowledge on this atretic effect, using a qualitative and quantitative histomorphological approach, we studied zebrafish ovarian follicular stage development in response to low BPA concentrations. Results show that BPA interferes with follicular progression by affecting the previtellogenic and vitellogenic phases. In particular, BPA exposure (i) increases follicular recruitment by acting on primary stage follicles, (ii) forces the follicular transition from stage III to stage IV producing enlarged stage IV follicles, and (iii) induces atresia by producing atretic follicles that are peculiarly enlarged (i.e., big atretic follicles). We suggest that BPA induces atresia by the primary effect on recruitment of stage I follicles. This forces follicular progression and produces stage IV follicles that are peculiarly enlarged that undertake the atretic development.

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Clark, L. J., H. F. Irving-Rodgers, A. M. Dharmarajan, and R. J. Rodgers. "206.Cell death of the theca interna during bovine ovarian follicular atresia." Reproduction, Fertility and Development 16, no. 9 (2004): 206. http://dx.doi.org/10.1071/srb04abs206.

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It is generally accepted that death of cells within the theca interna occurs late during ovarian follicular atresia. Histological classifications of atresia are usually based solely upon the morphology of the membrana granulosa. Atresia of bovine antral follicles less than 5 mm in diameter has been redefined as either antral or basal atresia depending on where in the membrana granulosa cell death is initiated. The aim of present study was to investigate changes within the theca interna during both antral and basal atresia. Bovine ovaries were collected and processed for light microscopy and immunohistochemistry. Each follicle less then 5 mm was classified as either healthy, antral atretic or basal atretic, with antral atresia being further classified either early-mid or late stage. Sections were labelled by TUNEL to identify dead cells combined with lectin from Bandeiraea simplificifolia to identify endothelial cells or with an antibody to cytochrome P450 cholesterol side-chain cleavage to identify steroidogenic cells. The numerical density of steroidogenic cells within the theca interna was significantly reduced (P < 0.001) in basal atretic follicles compared to healthy and antral atretic follicles. In both antral and basal atresia there was death of endothelial cells and steroidogenic cells. However cell death was greater in endothelial cells (P < 0.05) and steroidogenic cells (P < 0.001) of the theca interna of basal atretic follicles. There was no significant difference in the amount of cell death in the membrana granulosa between early-mid antral atresia and basal atresia while death of the membrana granulosa was significantly increased in late antral atresia compared to basal atresia (P < 0.01). Therefore we conclude that basal atresia is not a progression of antral atresia and that the theca interna can be susceptible to cell death early in atresia in basal atretic follicles.

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Zhang, Jinbi, Yang Liu, Wang Yao, Qifa Li, Honglin Liu, and Zengxiang Pan. "Initiation of follicular atresia: gene networks during early atresia in pig ovaries." Reproduction 156, no. 1 (July 2018): 23–33. http://dx.doi.org/10.1530/rep-18-0058.

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In mammals, more than 99% of ovarian follicles undergo a degenerative process known as atresia. The molecular events involved in atresia initiation remain incompletely understood. The objective of this study was to analyze differential gene expression profiles of medium antral ovarian follicles during early atresia in pig. The transcriptome evaluation was performed on cDNA microarrays using healthy and early atretic follicle samples and was validated by quantitative PCR. Annotation analysis applying current database (Sus scrofa 11.1) revealed 450 significantly differential expressed genes between healthy and early atretic follicles. Among them, 142 were significantly upregulated in early atretic with respect to healthy group and 308 were downregulated. Similar expression trends were observed between microarray data and quantitative RT-PCR confirmation, which indicated the reliability of the microarray analysis. Further analysis of the differential expressed genes revealed the most significantly affected biological functions during early atresia including blood vessel development, regulation of DNA-templated transcription in response to stress and negative regulation of cell adhesion. The pathway and interaction analysis suggested that atresia initiation associates with (1) a crosstalk of cell apoptosis, autophagy and ferroptosis rather than change of typical apoptosis markers, (2) dramatic shift of steroidogenic enzymes, (3) deficient glutathione metabolism and (4) vascular degeneration. The novel gene candidates and pathways identified in the current study will lead to a comprehensive view of the molecular regulation of ovarian follicular atresia and a new understanding of atresia initiation.

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Rodgers, R. J., and H. F. Irving-Rodgers. "Morphological classification of bovine ovarian follicles." REPRODUCTION 139, no. 2 (February 2010): 309–18. http://dx.doi.org/10.1530/rep-09-0177.

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Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles <5 mm diameter, half of the healthy follicles have columnar shaped basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section (‘loopy’). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes >5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles <5 mm are either basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles >5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective.

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Yao, Jinwei, Yanfen Ma, Shuo Zhou, Tingting Bao, Yuling Mi, Weidong Zeng, Jian Li, and Caiqiao Zhang. "Metformin Prevents Follicular Atresia in Aging Laying Chickens through Activation of PI3K/AKT and Calcium Signaling Pathways." Oxidative Medicine and Cellular Longevity 2020 (November 26, 2020): 1–23. http://dx.doi.org/10.1155/2020/3648040.

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Increased follicular atresia occurs with aging and results in reduced fecundity in laying chickens. Therefore, relieving follicular atresia of aging poultry is a crucial measure to maintain sustained high laying performance. As an antiaging agent, metformin was reported to play important roles in preventing aging in diverse animals. In this study, the physiological state of the prehierarchical follicles in the peak-laying hens (D280) and aged hens (D580) was compared, followed with exploration for the possible capacity of metformin in delaying atresia of the prehierarchical follicles in the aged D580 hens. Results showed that the capacity of yolk deposition within follicles declined with aging, and the point of endoplasmic reticulum- (ER-) mitochondrion contact decreased in the ultrastructure of the follicular cells. Meanwhile, the expression of apoptosis signaling genes was increased in the atretic small white follicles. Subsequently, the H2O2-induced follicular atresia model was established to evaluate the enhancing capacity of metformin on yolk deposition and inhibition of apoptosis in the atretic small white follicles. Metformin inhibited apoptosis through regulating cooperation of the mitochondrion-associated ER membranes and the insulin (PI3K/AKT) signaling pathway. Furthermore, metformin regulated calcium ion homeostasis to relieve ER-stress and inhibited release of mitochondrion apoptosis factors (BAD and caspase). Additionally, metformin activated PI3K/AKT that suppressed activation of BAD (downstream of the insulin signaling pathway) in the atretic follicles. Further, serum estrogen level and liver estrogen receptor-α expression were increased after dietary metformin supplementation in D580 hens. These results indicated that administration of dietary metformin activated the PI3K/AKT and calcium signaling pathway and enhanced yolk deposition to prevent chicken follicular atresia.

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Mokhtar, Doaa M., and Marwa M. Hussein. "Microanalysis of Fish Ovarian Follicular Atresia: A Possible Synergic Action of Somatic and Immune Cells." Microscopy and Microanalysis 26, no. 3 (May 12, 2020): 599–608. http://dx.doi.org/10.1017/s1431927620001567.

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AbstractThe present study describes in detail the morphological characteristics of the process of ovarian follicular atresia in Redbelly tilapia (Coptodon zillii) during the nonbreeding season using light and electron microscopy and immunohistochemistry. The follicular regression process was initiated with shrinkage and disintegration of the nuclear membrane of oocytes resulting in dispersing of chromatin within the ooplasm, followed by marked hyperplasia and hypertrophy of follicular and granulosa cells, which exhibited a strong phagocytic activity to engulf the liquefied yolk particles. Rodlet cells and granulocytes were recorded on the follicular wall and invaded the regressed follicles. Rodlet cells expressed a strong immunoreactivity to matrix metalloperoxidase (MMP-9) and α-smooth muscle actin, while neutrophils expressed a strong reactivity to Myeloperoxidase-3 (MPO). In the advanced stage of follicular atresia, the yolk was almost phagocytized and resorbed and the regressed follicle lost its integrity and appeared to be formed of a cellular mass of phagocytic cells. Transmission electron microscopy revealed the presence of neutrophils, eosinophils, and dendritic cells within the atretic follicle in between these phagocytic cells. Moreover, numerous lysosomes, granules, and phagosomes were observed within the cytoplasm of both phagocytic cells and granulocytes. Telocytes were also demonstrated within the highly thickened richly vascularized theca layer during the late stages of follicular atresia. Immunohistochemical staining for caspase-3 established the participation of apoptosis in the advanced stages of follicular regression. Immune cells, rodlet cells, and telocytes in combination with follicular cells play an essential role in follicular atresia. In conclusion, the present study provides a new evidence on the role of both somatic and immune cells in the phenomenon of ovarian follicular atresia in Redbelly tilapia (Coptodon zillii) during the nonbreeding season.

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Ortega-Camarillo, Clara, Alicia González-González, Marcela Vergara-Onofre, Everardo González-Padilla, Alejandro Ávalos-Rodríguez, Margarita E. Gutiérrez-Rodríguez, Lourdes Arriaga-Pizano, Miguel Cruz, Luís Arturo Baiza-Gutman, and Margarita Díaz-Flores. "Changes in the glucose-6-phosphate dehydrogenase activity in granulosa cells during follicular atresia in ewes." REPRODUCTION 137, no. 6 (June 2009): 979–86. http://dx.doi.org/10.1530/rep-08-0463.

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Apoptosis of granulosa cells during follicular atresia is preceded by oxidative stress, partly due to a drop in the antioxidant glutathione (GSH). Under oxidative stress, GSH regeneration is dependent on the adequate supply of NADPH by glucose-6-phosphate dehydrogenase (G6PD). In this study, we analyzed the changes of G6PD, GSH, and oxidative stress of granulosa cells and follicular liquid and its association with apoptosis during atresia of small (4–6 mm) and large (>6 mm) sheep antral follicles. G6PD activity was found to be higher in granulosa cells of healthy small rather than large follicles, with similar GSH concentration in both cases. During atresia, increased apoptosis and protein oxidation, as well as a drop in GSH levels, were observed in follicles of both sizes. Furthermore, the activity of G6PD decreased in atretic small follicles, but not in large ones. GSH decreased and protein oxidation increased in follicular fluid. This was dependent on the degree of atresia, whereas the changes in G6PD activity were based on the type of follicle. The higher G6PD activity in the small follicles could be related to granulosa cell proliferation, follicular growth, and a lower sensitivity to oxidative stress when compared with large follicles. The results also indicate that GSH concentration in atretic follicles depends on other factors in addition to G6PD, such asde novosynthesis or activity of other NADPH-producing enzymes. Finally, lower G6PD activity in large follicles indicating a higher susceptibility to oxidative stress associated to apoptosis progression in follicle atresia.

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Terenina, Elena, Stephane Fabre, Agnès Bonnet, Danielle Monniaux, Christèle Robert-Granié, Magali SanCristobal, Julien Sarry, et al. "Differentially expressed genes and gene networks involved in pig ovarian follicular atresia." Physiological Genomics 49, no. 2 (February 1, 2017): 67–80. http://dx.doi.org/10.1152/physiolgenomics.00069.2016.

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Ovarian folliculogenesis corresponds to the development of follicles leading to either ovulation or degeneration, this latter process being called atresia. Even if atresia involves apoptosis, its mechanism is not well understood. The objective of this study was to analyze global gene expression in pig granulosa cells of ovarian follicles during atresia. The transcriptome analysis was performed on a 9,216 cDNA microarray to identify gene networks and candidate genes involved in pig ovarian follicular atresia. We found 1,684 significantly regulated genes to be differentially regulated between small healthy follicles and small atretic follicles. Among them, 287 genes had a fold-change higher than two between the two follicle groups. Eleven genes ( DKK3, GADD45A, CAMTA2, CCDC80, DAPK2, ECSIT, MSMB, NUPR1, RUNX2, SAMD4A, and ZNF628) having a fold-change higher than five between groups could likely serve as markers of follicular atresia. Moreover, automatic confrontation of deregulated genes with literature data highlighted 93 genes as regulatory candidates of pig granulosa cell atresia. Among these genes known to be inhibitors of apoptosis, stimulators of apoptosis, or tumor suppressors INHBB, HNF4, CLU, different interleukins ( IL5, IL24), TNF-associated receptor ( TNFR1), and cytochrome-c oxidase ( COX) were suggested as playing an important role in porcine atresia. The present study also enlists key upstream regulators in follicle atresia based on our results and on a literature review. The novel gene candidates and gene networks identified in the current study lead to a better understanding of the molecular regulation of ovarian follicular atresia.

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Gao, Xiaomeng, Jinbi Zhang, Zengxiang Pan, Qifa Li, and Honglin Liu. "The distribution and expression of vascular endothelial growth factor A (VEGFA) during follicular development and atresia in the pig." Reproduction, Fertility and Development 32, no. 3 (2020): 259. http://dx.doi.org/10.1071/rd18508.

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The involvement of vascular endothelial growth factor A (VEGFA) in ovarian physiological processes has been widely reported, but the location and role of VEGFA during follicular atresia remain unknown. This study investigated the distribution and expression of VEGFA during porcine follicular development and atresia. Pig ovaries were obtained, individual medium-sized (3–5mm in diameter) antral follicles were separated and classified into healthy, early atretic or progressively atretic groups. Immunobiology and quantitative techniques were used to investigate the varied follicular distribution of VEGFA at both the morphological and molecular level. The results indicated that VEGFA protein expression peaked in tertiary follicles, mostly distributed in the thecal and inner granulosa layers, during follicular development while VEGFA mRNA was mainly expressed in the inner granulosa layers. Additionally, healthy antral follicles showed a significantly higher expression of VEGFA than atretic follicles in both theca and granulosa cells. Knockdown of VEGFA using siRNA revealed an antiapoptosis effect of VEGFA in cultured pig granulosa cells. Our results increase the knowledge of VEGFA functions in follicles.

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Vlčková, Radoslava, Drahomíra Sopková, Ján Pošivák, and Igor Valocký. "Ovarian Follicular Atresia of Ewes during Spring Puerperium." Veterinary Medicine International 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/638928.

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The distribution of healthy and atretic follicles on the ovarian surface of improved Valachian ewes 17, 24, and 32 days postpartum is reported in this study. The number of healthy follicles was higher on day 24 postpartum and their mean diameter tended to increase to day 32 (P<0.05) with the greatest diameter of 5 mm. 78–81% of atretic follicles ≥3 mm in diameter was observed where apoptosis began in the follicular cells situated at the follicular cavity. The early atretic follicles are characterized by the presence of mitotic pictures. In one ewe 24 days postpartum, small regressive follicular cysts were observed. Contracting atresia is characterized by thickening of the theca interna even to 190 μm. Progesterone and oestradiol-17βconcentrations were maintained at relatively low levels, but with no significant difference between the days postpartum.

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Leidy, Lynnette E., Laurie R. Godfrey, and Michael R. Sutherland. "Is follicular atresia biphasic?" Fertility and Sterility 70, no. 5 (November 1998): 851–59. http://dx.doi.org/10.1016/s0015-0282(98)00316-1.

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Irving-Rodgers, H. F., K. D. Catanzariti, M. Master, P. A. Grant, P. C. Owens, and R. J. Rodgers. "Insulin-like growth factor binding proteins in follicular fluid from morphologically distinct healthy and atretic bovine antral follicles." Reproduction, Fertility and Development 15, no. 4 (2003): 241. http://dx.doi.org/10.1071/rd03008.

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In bovine follicles 2–5 mm in diameter, two morphologically distinct types of healthy follicles and two types of atretic follicles have been described recently. Healthy follicles either have columnar basal granulosa cells with follicular basal lamina composed of many layers or ‘loops’ or they have rounded basal cells with a conventional single-layered, aligned follicular basal lamina. In atretic follicles, cell death either commences at the basal layer and progresses to the antrum (basal atresia) with macrophage penetration of the membrana granulosa or death progresses from the antrum in a basal direction (antral atresia). Little is known about how these different phenotypes develop. To determine whether insulin-like growth factor binding protein (IGFBP) levels in follicular fluid differ between these different types of follicles, we measured IGFBP levels in fluids from these follicles. A total of 61 follicles were assessed by light microscopy and characterized by morphological analysis as either healthy, with columnar or rounded basal granulosa cells, or as undergoing antral or basal atresia. The IGFBP concentration in the follicular fluid of individual follicles from the four groups (n = 12–20 per group) was identified by Western ligand blots using 125I-insulin-like growth factor (IGF)-II as a probe. Insulin-like growth factor binding proteins 2, 3 (44 and 40 kDa), 4 (glycosylated and non-glycosylated) and 5 were observed. The levels (per volume of fluid) of IGFBPs 2, 4 and 5 were greater in atretic follicles than in healthy follicles. However, there were no statistical differences in levels of each IGFBP between either the two types of healthy follicle or between the two types of atretic follicles. Thus, IGFBP levels are not related to the different types of healthy or atretic follicles.

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JIN, Xuan. "Follicular growth, differentiation and atresia." Chinese Science Bulletin 48, no. 17 (2003): 1786. http://dx.doi.org/10.1360/03wc0088.

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Jin, Xuan, and Yixun Liu. "Follicular growth, differentiation and atresia." Chinese Science Bulletin 48, no. 17 (September 2003): 1786–90. http://dx.doi.org/10.1007/bf03184054.

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Chitnis, Swati S., Rajshri M. Navlakhe, Gayatri C. Shinde, Sharmila J. Barve, Serena D'Souza, Smita D. Mahale, and Tarala D. Nandedkar. "Granulosa Cell Apoptosis Induced by a Novel FSH Binding Inhibitory Peptide From Human Ovarian Follicular Fluid." Journal of Histochemistry & Cytochemistry 56, no. 11 (July 21, 2008): 961–68. http://dx.doi.org/10.1369/jhc.2008.951475.

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Pituitary gonadotropins, follicle-stimulating hormone and luteinizing hormone, are the key regulators of ovarian folliculogenesis; these are known to be directly or indirectly modulated by many intraovarian factors. Our group has identified and studied one such novel peptide from human ovarian follicular fluid. Its partial N-terminal eight amino acid sequence has been deduced, referred to as octapeptide (OP). OP induces follicular atresia in mice and interferes with normal ovarian function in non-human primates, this action being similar to the native peptide. Thus, in this study, an attempt has been made to elucidate the mechanism of action of the synthetic OP by studying the pathway of follicular atresia in mouse ovary. Changes in granulosa cells were studied using various apoptotic markers by flow cytometry and immunohistochemistry. An increase in apoptotic cell population in atretic- and peptide-treated groups was observed compared with normal controls. Interestingly, both these groups exhibited differences in the apoptotic pathway. Results showed that the mitochondrial pathway was predominant in the atretic group, whereas the Fas-FasL pathway was predominant in the peptide-treated groups. The ultrastructural study also showed apoptotic changes in the OP-treated and atretic groups; the pattern of apoptosis differed at the subcellular level.

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Zhuo, Yong, Meng Cao, Yuechan Gong, Lianchao Tang, Xuemei Jiang, Yang Li, Min Yang, et al. "Gut microbial metabolism of dietary fibre protects against high energy feeding induced ovarian follicular atresia in a pig model." British Journal of Nutrition 125, no. 1 (June 30, 2020): 38–49. http://dx.doi.org/10.1017/s0007114520002378.

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AbstractTo investigate the effects of dietary fibre on follicular atresia in pigs fed a high-fat diet, we fed thirty-two prepubescent gilts a basal diet (CON) or a CON diet supplemented with 300 g/d dietary fibre (fibre), 240 g/d soya oil (SO) or both (fibre + SO). At the 19th day of the 4th oestrus cycle, gilts fed the SO diet showed 112 % more atretic follicles and greater expression of the apoptotic markers, Bax and caspase-3, and these effects were reversed by the fibre diet. The abundance of SCFA-producing microbes was decreased by the SO diet, but this effect was reversed by fibre treatment. Concentrations of serotonin and melatonin in the serum and follicular fluid were increased by the fibre diet. Overall, dietary fibre protected against high fat feeding-induced follicular atresia at least partly via gut microbiota-related serotonin–melatonin synthesis. These results provide insight into preventing negative effects on fertility in humans consuming a high-energy diet.

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Meng, Li, Zhenfang Wu, Kun Zhao, Jian Tao, Tam Chit, Shouquan Zhang, Chi Chiu Wang, and Katja Teerds. "Transcriptome Analysis of Porcine Granulosa Cells in Healthy and Atretic Follicles: Role of Steroidogenesis and Oxidative Stress." Antioxidants 10, no. 1 (December 28, 2020): 22. http://dx.doi.org/10.3390/antiox10010022.

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One of the main causes of female infertility is a deregulated antral follicular atresia, a process of which the underlying molecular mechanisms are largely unknown. Our objective was therefore to characterize the complex transcriptome changes in porcine granulosa cells of healthy antral (HA) and advanced antral atretic (AA) follicles, using ELISA and RNA-Seq followed by qRT-PCR and immunohistochemistry. Granulosa cell RNA-Seq data revealed 2160 differentially expressed genes, 1483 with higher and 677 with lower mRNA concentrations in AA follicles. Bioinformatic analysis showed that the upregulated genes in AA follicles were highly enriched in inflammation and apoptosis processes, while the downregulated transcripts were mainly highlighted in the steroid biosynthesis pathway and response to oxidative stress processes including antioxidant genes (e.g., GSTA1, GCLC, GCLM, IDH1, GPX8) involved in the glutathione metabolism pathway and other redox-related genes (e.g., RRM2B, NDUFS4). These observations were confirmed by RT-qPCR and immunohistochemistry. Additionally, the granulosa cells of AA follicles express significantly stronger 8-OHdG immunostaining, a marker of oxidative DNA damage, implicating that oxidative stress may participate in follicular atresia. We hypothesize that the decrease in anti-apoptotic factors and steroid hormones coincides with increased oxidative stress markers and the expression of pro-apoptotic factors, all contributing to antral follicular atresia.

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Nezis, Ioannis P., Dimitrios J. Stravopodis, Lukas H. Margaritis, and Issidora S. Papassideri. "Follicular atresia during Dacus oleae oogenesis." Journal of Insect Physiology 52, no. 3 (March 2006): 282–90. http://dx.doi.org/10.1016/j.jinsphys.2005.11.007.

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Ma, Mengnan, Jinbi Zhang, Xiaomeng Gao, Wang Yao, Qifa Li, and Zengxiang Pan. "miR-361-5p Mediates SMAD4 to Promote Porcine Granulosa Cell Apoptosis through VEGFA." Biomolecules 10, no. 9 (September 4, 2020): 1281. http://dx.doi.org/10.3390/biom10091281.

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Follicular atresia is an inevitable degenerative process that occurs in mammalian ovarian follicles. The molecular events involved in atresia, particularly granulosa cell apoptosis, have long attracted researchers’ attention. Vascular endothelial growth factor A (VEGFA) is downregulated during follicular atresia in porcine ovaries and serves as an inhibitor of apoptosis in granulosa cells. In addition, transforming growth factor (TGF)-βsignaling has been considered a central trigger in granulosa cell apoptosis. However, the link between TGF-β signaling and VEGFA is unknown. We proved that miR-361-5p is significantly upregulated during the atresia process and that it promotes GC apoptosis by directly targeting the VEGFA 3′UTR. In addition, we revealed that the miR-361-5p coding gene MIR361 was significantly downregulated by SMAD4, the central intracellular mediator of TGF-β signaling, that bound to the MIR361 promoter. In conclusion, our findings expanded what is known about VEGFA posttranscriptional regulation and revealed a complete SMAD4/miR-361-5p/VEGFA regulatory network in ovarian granulosa cell apoptosis. These data provide useful references for follicular atresia and ovarian physiological function studies.

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Armstrong, D. G. "Changes in aromatase activity in small ovarian follicles of the domestic fowl (Gallus domesticus) during growth and atresia." Journal of Endocrinology 105, no. 3 (June 1985): 297–301. http://dx.doi.org/10.1677/joe.0.1050297.

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ABSTRACT The tritium release assay for measuring aromatase activity was adapted to measure oestrogen production in intact small ovarian follicles of the domestic fowl. The activity was measured in three types of follicle classified as normal, atretic or grossly atretic. Normal follicles were distinguished from atretic by the presence of small haemorrhages on the surface of the atretic follicles. Grossly atretic follicles were identified by their deformed shape. The aromatase activity in normal and atretic follicles was related to follicular weight, the activity in atretic follicles being less than that in normal follicles. The aromatase activity in grossly atretic follicles was independent of follicular weight. The enzyme activity in this group of follicles was significantly less than that in either normal or atretic follicles. The significance of these results is discussed in relation to the induction of atresia within the small ovarian follicles of the domestic fowl. J. Endocr. (1985) 105, 297–301

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Yang, Feng, Yanhong Chen, Qiang Liu, Shizhen Dai, and Shenming Zeng. "Dynamics and Regulations of BimEL Ser65 and Thr112 Phosphorylation in Porcine Granulosa Cells during Follicular Atresia." Cells 9, no. 2 (February 10, 2020): 402. http://dx.doi.org/10.3390/cells9020402.

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BimEL protein is involved in follicular atresia by regulating granulosa cell apoptosis, but the dynamic changes of BimEL phosphorylation during follicular atresia are poorly understood. The aim of this study was to explore the changes of key BimEL phosphorylation sites and their upstream regulatory pathways. First, the levels of BimEL-Ser65 and BimEL-Thr112 phosphorylation (p-BimEL-S65, p-BimEL-T112) in granulosa cells (GC) from healthy (H), slightly-atretic (SA), and atretic (A) follicles and in cultured GC after different treatments were detected by Western blotting. Next, the effects of the corresponding site mutations of BIM on apoptosis of GC were investigated. Finally, the pathways of two phosphorylation sites were investigated by kinase inhibitors. The results revealed that p-BimEL-S65 levels were higher in GC from H than SA and A, whereas p-BimEL-T112 was reversed. The prosurvival factors like FSH and IGF-1 upregulated the level of p-BimEL-S65, while the proapoptotic factor, heat stress, increased the level of p-BimEL-T112 in cultured GC. Compared with the overexpression of wild BimEL, the apoptotic rate of the GC overexpressed BimEL-S65A (replace Ser65 with Ala) mutant was significantly higher, but the apoptotic rate of the cells overexpressing BimEL-T112A did not differ. In addition, inhibition of the ERK1/2 or JNK pathway by specific inhibitors reduced the levels of p-BimEL-S65 and p-BimEL-T112. In conclusion, the levels of p-BimEL-S65 and p-BimEL-T112 were reversed during follicular atresia. Prosurvival factors promote p-BimEL-S65 levels via ERK1/2 to inhibit GC apoptosis, whereas proapoptotic factor upregulates the level of p-BimEL-T112 via JNK to induce GC apoptosis.

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Ostuni, Angela, Maria Pina Faruolo, Carmen Sileo, Agata Petillo, and Raffaele Boni. "Effect of follicle size and atresia grade on mitochondrial membrane potential and steroidogenic acute regulatory protein expression in bovine granulosa cells." Zygote 26, no. 6 (December 2018): 476–84. http://dx.doi.org/10.1017/s0967199418000564.

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SummaryDuring follicular development, granulosa cells undergo functional and structural changes affecting their steroidogenic activity. Oestrogen synthesis mainly occurs in the endoplasmic reticulum and relies on aromatase activity to convert androgens that arise from theca cells. In the present study, indicators of mitochondria-related steroidogenic capacity, as steroidogenic acute regulatory (StAR) protein expression and mitochondrial membrane potential (MMP), have been evaluated in bovine granulosa cells (GCs) and related to follicle growth and atresia. Atresia was estimated by morphological examination of follicle walls and cumulus–oocyte complexes (COC) and assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay for apoptosis detection. Bovine ovarian follicles were macroscopically classified according to their atresia grade and grouped into small, medium or large follicles. After follicle opening, the COCs were morphologically classified for follicle atresia and the GCs were collected. Granulosa cells were fixed for immunofluorescence (IF) and TUNEL assay, frozen for western blotting (WB) or freshly maintained for MMP analyses. StAR protein expression was assessed using both IF and WB analyses. The follicle atresia grade could be efficiently discriminated based on either follicle wall or COC morphological evaluations. Granulosa cells collected from small non-atretic follicles showed a higher (P <0.01) MMP and WB-based StAR protein expression than small atretic follicles. For IF analysis, StAR protein expression in large atretic follicles was higher (P <0.05) than that in large non-atretic follicles. These results suggest a role played by mitochondria in GC steroidogenic activity, which declines in healthy follicles along with their growth. In large follicles, steroidogenic activity increases with atresia and is possibly associated with progesterone production.

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Orimoto, Adriana M., Karine Dumaresq-Doiron, Jin-Yi Jiang, Nongnuj Tanphaichitr, Benjamin K. Tsang, and Euridice Carmona. "Mammalian Hyaluronidase Induces Ovarian Granulosa Cell Apoptosis and Is Involved in Follicular Atresia." Endocrinology 149, no. 11 (July 24, 2008): 5835–47. http://dx.doi.org/10.1210/en.2008-0175.

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During ovarian folliculogenesis, the vast majority of follicles will undergo atresia by apoptosis, allowing a few dominant follicles to mature. Mammalian hyaluronidases comprise a family of six to seven enzymes sharing the same catalytic domain responsible for hyaluronan hydrolysis. Interestingly, some of these enzymes have been shown to induce apoptosis. In the ovary, expression of three hyaluronidases (Hyal-1, Hyal-2, and Hyal-3) has been documented. However, their precise cellular localization and role in ovarian regulation have not yet been defined. We herein investigated the possible involvement of these enzymes in ovarian atresia. First, we established a mouse model for ovarian atresia (gonadotropin withdrawal by anti-equine chorionic gonadotropin treatment) and showed that the mRNA levels of Hyal-1, Hyal-2, and Hyal-3 were significantly increased in apoptotic granulosa cells as well as in atretic follicles. Second, using ovaries of normally cycling mice, we demonstrated the correlation of Hyal-1 mRNA and protein expression with cleavage of caspase-3. In addition, we showed that expression of all three hyaluronidases induced apoptosis in transfected granulosa cells. Significantly, the induction of apoptosis by hyaluronidases was independent of catalytic activity, because enzymatically inactive Hyal-1 mutant (D157A/E159A) was as efficient as the wild-type enzyme in apoptosis induction. The activation of the extrinsic apoptotic signaling pathway was involved in this induction, because increased levels of cleaved caspase-8, caspase-3, and poly-ADP-ribose polymerase (PARP) were observed upon hyaluronidase ectopic expression. Our present findings provide a better understanding of the role of hyaluronidases in ovarian functions, showing for the first time their involvement in follicular atresia.

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Douglas, H. R., I. C. Kokay, D. R. Grattan, and P. R. Hurst. "335. X-LINKED INHIBITOR OF APOPTOSIS PROTEIN (XIAP) EXPRESSION PATTERNS IN THE SHEEP OVARY." Reproduction, Fertility and Development 22, no. 9 (2010): 135. http://dx.doi.org/10.1071/srb10abs335.

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At reproductive age, the ovary undergoes continual cyclicity of follicles due to multiple positive and negative signals that promote follicle growth and development, selection for ovulation, or atresia. The majority of follicles undergo atresia, a degenerative process involving granulosa cell apoptosis. This process is executed by caspases, which are cysteine proteases. Caspases are potently inhibited by XIAP providing a potential mechanism to control follicular atresia. The study objective was to test the hypothesis that XIAP will show elevated expression in healthy antral follicles compared to atretic antral follicles and will show an inverse relationship with active caspase-3 immunoreactivity in the same antral follicle during the sheep estrous cycle. Reproductively mature Romney ewes (n = 9) had estrous cycles synchronized with a prostaglandin F2α analogue, then tissue was collected on days 14, 15 and 16 of the subsequent natural cycle. Analysis involved determining the presence and localization of XIAP using in situ hybridization histochemistry and immunohistochemistry then comparing XIAP expression patterns with distribution of active caspase-3 protein. XIAP mRNA was not detected in primordial, primary and secondary follicles. In contrast, XIAP protein was present from the primary stage onwards. Antral follicles showed positive XIAP mRNA and protein expression in both granulosa and thecal cell layers and antral follicles on the same tissue section showed variable expression. All day 14 antral follicles were positive for XIAP mRNA expression irrespective of the level of active caspase-3 immunoreactivity, whereas an inverse relationship between active caspase-3 and XIAP was apparent in the majority of day 15 and 16 antral follicles. XIAP protein was widely expressed in active caspase-3 negative antral follicles and indicated a negative correlation with the onset of active caspase-3 expression in the majority of follicles. These results indicate that XIAP may regulate follicular atresia and act as an indicator of follicular health in the sheep ovary.

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Cao, Mingju, José Buratini, Jacques G. Lussier, Paul D. Carrière, and Christopher A. Price. "Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle." Reproduction 131, no. 1 (January 2006): 125–37. http://dx.doi.org/10.1530/rep.1.00849.

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Extracellular matrix remodeling occurs during ovarian follicular development, mediated by plasminogen activators (PAs) and PA inhibitors including protease nexin-1 (PN-1). In the present study we measured expression/activity of the PA system in bovine follicles at different stages of development by timed collection of ovaries during the first follicular wave and during the periovulatory period, and in follicles collected from an abattoir. The abundance of mRNA encoding PN-1, tissue-type PA (tPA), urokinase (uPA) and PA inhibitor-1 (PAI-1) were initially upregulated by human chorionic gonadotropin (hCG) in bovine preovulatory follicular wall homogenates. PN-1, PAI-1 and tPA mRNA expression then decreased near the expected time of ovulation, whereas uPA mRNA levels remained high. PN-1 concentration in follicular fluid (FF) decreased and reached the lowest level at the time of ovulation, whereas plasmin activity in FF increased significantly after hCG. Follicles collected from the abattoir were classified as non-atretic, early-atretic or atretic based on FF estradiol and progesterone content: PN-1 protein levels in FF were significantly higher in non-atretic than in atretic follicles, and plasmin activity was correspondingly higher in the atretic follicles. No changes in PN-1 levels in FF were observed during the growth of pre-deviation follicles early in a follicular wave. These results indicate that PN-1 may be involved in the process of atresia in non-ovulatory dominant follicles and the prevention of precocious proteolysis in periovulatory follicles.

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Guthrie, H. D., R. W. Grimes, B. S. Cooper, and J. M. Hammond. "Follicular atresia in pigs: measurement and physiology." Journal of Animal Science 73, no. 9 (1995): 2834. http://dx.doi.org/10.2527/1995.7392834x.

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Zhou, Jiawei, Xianwen Peng, and Shuqi Mei. "Autophagy in Ovarian Follicular Development and Atresia." International Journal of Biological Sciences 15, no. 4 (2019): 726–37. http://dx.doi.org/10.7150/ijbs.30369.

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Rune, Gabriele M. "Hydrolase cytochemistry during follicular atresia in mammals." Acta Histochemica 83, no. 1 (January 1988): 71–80. http://dx.doi.org/10.1016/s0065-1281(88)80074-6.

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De Felici, Massimo. "Ovarian follicular atresia: a model for apoptosis." Cell Death & Differentiation 4, no. 3 (April 1997): 260–61. http://dx.doi.org/10.1038/sj.cdd.4400236.

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Seifer, David B., and Zaher Merhi. "Is AMH a regulator of follicular atresia?" Journal of Assisted Reproduction and Genetics 31, no. 11 (September 6, 2014): 1403–7. http://dx.doi.org/10.1007/s10815-014-0328-7.

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Rodgers, Raymond J., and Joop S. E. Laven. "Genetic relationships between early menopause and the behaviour of theca interna during follicular atresia." Human Reproduction 35, no. 10 (August 13, 2020): 2185–87. http://dx.doi.org/10.1093/humrep/deaa173.

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ABSTRACT Genetic variants are known to contribute to about 50% of the heritability of the age of menopause and recent studies suggest that genes associated with genome maintenance are involved. The idea that increased rates of follicular atresia could lead to depletion of the primoridial follicle reserve and early menopause has also been canvassed, but there is no direct evidence of this. In studies of the transcriptomics of follicular atresia, it was found that in the theca interna, the largest group of genes are in fact down-regulated and associated with ‘cell cycle and DNA replication’, in contrast with the up-regulation of apoptosis-associated genes which occurs in granulosa cells. Many of the genes down-regulated in the theca interna are the same as or related to the genes in loci associated with early menopause. From these findings, we suggest that early menopause could be due to increased rates of follicular atresia initiated from the theca interna.

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Slot, Karin A., Jan Kastelijn, Anne Bachelot, Paul A. Kelly, Nadine Binart, and Katja J. Teerds. "Reduced recruitment and survival of primordial and growing follicles in GH receptor-deficient mice." Reproduction 131, no. 3 (March 2006): 525–32. http://dx.doi.org/10.1530/rep.1.00946.

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GH influences female fertility. The goal of the present study was to obtain more insight into the effect of loss of GH signalling, as observed in humans suffering from Laron syndrome, on ovarian function. Therefore, serial paraffin sections of ovaries of untreated and IGF-I-treated female GH receptor knock-out (GHR/GHBP-KO) mice were examined to determine the follicular reserve and the percentage of follicular atresia in each ovary. Our observations demonstrate that the amount of primordial follicles was significantly elevated in GHR/GHBP-KO mice, while the numbers of primary, preantral and antral follicles were lower compared with wild-type values. The reduced number of healthy growing follicles in GHR/GHBP-KO mice was accompanied by a significant increase in the percentage of atretic follicles. IGF-I treatment of GHR/GHBP-KO mice for 14 days resulted in a reduced number of primordial follicles, an increased number of healthy antral follicles, and a decreased percentage of atretic follicles. The results of the present study suggest that GH may play a role, either directly or indirectly, via for instance IGF-I, in the recruitment of primordial follicles into the growing pool. Furthermore, GH seems to protect antral follicles, directly or indirectly from undergoing atresia.

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VIANA, JOÃO HENRIQUE MOREIRA, ADEMIR DE MORAES FERREIRA, WANDERLEI FERREIRA DE SÁ, and LUIZ SÉRGIO DE ALMEIDA CAMARGO. "Follicular dynamics in zebu cattle." Pesquisa Agropecuária Brasileira 35, no. 12 (December 2000): 2501–9. http://dx.doi.org/10.1590/s0100-204x2000001200021.

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The aim of this study was to investigate the follicular dynamics during estrous cycle in Gir breed (Bos indicus) cows. Follicular growth and atresia during estrous cycle were evaluated using a portable ultrasound device. Luteal activity was evaluated by serum progesterone levels. Cycles with two (6.67%), three (60.00%), four (26.67%) and five (6.67%) follicular waves were observed. There was no difference (P>0.05) in dominant or subordinate follicles growth or atresia rates among follicular waves. The maximum diameter of the ovulatory follicle was higher than the diameter of the other dominant follicles in cycles with four waves, and higher than the diameter of the second dominant follicle in cycles with three waves (P<0.05). There was no difference (P>0.05) in estrous cycle length (21.11±1.76 and 22.25±1.71 days) or progesterone levels during diestrous (4.48±1.45 and 5.08±1.40 ng/mL) between cycles with three or four waves. Follicular dynamics in Gir cattle is characterized by a higher incidence of cycles with three or four waves, associated with a low persistence of the dominant follicle.

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Alonso-Pozos, Israel, Ana Maria Rosales-Torres, Alejandro Ávalos-Rodrı́guez, Marcela Vergara-Onofre, and Adolfo Rosado-Garcı́a. "Mechanism of granulosa cell death during follicular atresia depends on follicular size." Theriogenology 60, no. 6 (October 2003): 1071–81. http://dx.doi.org/10.1016/s0093-691x(03)00123-7.

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Wang, Yingzheng, and Shenming Zeng. "Melatonin Promotes Ubiquitination of Phosphorylated Pro-Apoptotic Protein Bcl-2-Interacting Mediator of Cell Death-Extra Long (BimEL) in Porcine Granulosa Cells." International Journal of Molecular Sciences 19, no. 11 (November 1, 2018): 3431. http://dx.doi.org/10.3390/ijms19113431.

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Melatonin (N-acetyl-5-methoxytryptamine) is found in ovarian follicular fluid, and its concentration is closely related to follicular health status. Nevertheless, the molecular mechanisms underlying melatonin function in follicles are uncertain. In this study, melatonin concentration was measured in porcine follicular fluid at different stages of health. The melatonin concentration decreased as the follicles underwent atresia, suggesting that melatonin may participate in the maintenance of follicular health. The molecular pathway through which melatonin may regulate follicular development was further investigated. The pro-apoptotic protein BimEL (Bcl-2-interacting mediator of cell death-Extra Long), a key protein controlling granulosa cell apoptosis during follicular atresia, was selected as the target molecule. BimEL was downregulated when porcine granulosa cells were cultured in medium containing 10−9 M melatonin and isolated cumulus oocyte complexes (COCs) or follicle stimulating hormone (FSH). Interestingly, ERK-mediated phosphorylation was a prerequisite for the melatonin-induced decline in BimEL, and melatonin only promoted the ubiquitination of phosphorylated BimEL, and did not affect the activities of the lysosome or the proteasome. Moreover, the melatonin-induced downregulation of BimEL was independent of its receptor and its antioxidant properties. In conclusion, melatonin may maintain follicular health by inducing BimEL ubiquitination to inhibit the apoptosis of granulosa cells.

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Monniaux, D., P. Monget, JC Mariana, A. Nicolle, C. Pisselet, Y. Cognié, N. Poulin, J. Fontaine, and P. Durand. "Functional changes throughout follicular atresia in the ewe." Reproduction Nutrition Development 33, no. 1 (1993): 82–83. http://dx.doi.org/10.1051/rnd:19930112.

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Gumus, Basak. "Role of apoptosis-related factors in follicular atresia." International Journal of Genetics and Molecular Biology 5, no. 5 (October 30, 2013): 54–63. http://dx.doi.org/10.5897/ijgmb11.020.

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Asselin, Eric, Chao Wu Xiao, Yi Fang Wang, and Benjamin K. Tsang. "Mammalian Follicular Development and Atresia: Role of Apoptosis." Neurosignals 9, no. 2 (2000): 87–95. http://dx.doi.org/10.1159/000014627.

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39

Garside, Samantha A., Jack Henkin, Keith D. Morris, Suzanne M. Norvell, Fiona H. Thomas, and Hamish M. Fraser. "A Thrombospondin-Mimetic Peptide, ABT-898, Suppresses Angiogenesis and Promotes Follicular Atresia in Pre- and Early-Antral Follicles in Vivo." Endocrinology 151, no. 12 (September 29, 2010): 5905–15. http://dx.doi.org/10.1210/en.2010-0283.

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Using a novel in vitro angiogenesis assay, we previously showed that thrombospondin (TSP)-1 has antiangiogenic effects on rat follicles and induces apoptosis in granulosa cells in vitro. ABT-898 is an octapeptide mimetic of TSP-1 closely related to ABT-510. Here, we demonstrate the inhibitory effects of ABT-898 on follicular angiogenesis and its proapoptotic effect on granulosa cells. To investigate the potential of this peptide to inhibit follicular angiogenesis in vivo, marmoset monkeys were treated with 2.5 mg/kg ABT-898 twice daily throughout the follicular phase of the cycle. Although treatment did not block emergence of dominant follicles, angiogenesis was reduced in preantral and early-antral follicles. Furthermore, the incidence of atresia at these follicle stages was increased. To investigate whether treatment with ABT-898 would interfere with the timing or duration of the normal ovulatory rise in plasma progesterone, marmosets were treated with a depot formulation containing 25 mg ABT-898 at the start of the follicular phase, with a second injection after 2 wk. Despite active concentrations of peptide being maintained in the circulation, no apparent effects on the ovulatory cycle were observed. Taken together, these results indicate that ABT-898 is capable of having a dual effect by inhibiting follicular angiogenesis and promoting atresia of antral follicles in vivo but does not prevent ovulation or induce luteolysis, as has been observed with direct vascular endothelial growth factor inhibitors. These results suggest that ABT-898 could be a novel therapeutic to inhibit abnormal angiogenesis and induce atresia of accumulated follicles in polycystic ovary syndrome.

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Foghi, A., K. J. Teerds, H. van der Donk, and J. Dorrington. "Induction of apoptosis in rat thecal/interstitial cells by transforming growth factor α plus transforming growth factor β in vitro." Journal of Endocrinology 153, no. 1 (April 1997): 169–78. http://dx.doi.org/10.1677/joe.0.1530169.

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Abstract In each estrous cycle dominant follicles are selected from a growing pool to develop to the preovulatory stage and to ovulate. Those follicles that do not ovulate must be eliminated in order to maintain the constant mass and homeostasis of the ovary. Granulosa cells are lost by apoptosis at the onset of follicular atresia, whereas apoptotic thecal cells are identified at later stages of atresia. Since transforming growth factor (TGF) α and TGFβ1 have been implicated in the regulation of thecal cell physiology we have localized these growth factors by immunohistochemistry in sections of ovaries from 25-day-old rats, an age at which the ovary exhibits a wave of atresia of preantral follicles. Thecal cells contained TGFα and TGFβ1 throughout the entire process of follicular atresia. To determine if these growth factors could influence thecal cell death, thecal/interstitial cells were isolated from 25-day-old rats, and maintained in culture with growth factors. Subconfluent cultures treated with TGFα or TGFβ1 alone remained healthy whereas in the presence of both TGFα and TGFβ1 there was light microscopical evidence of rounding up of cells and detachment from the monolayer. Chromatin condensation and internucleosomal fragmentation, characteristic of apoptosis, were observed by nucleic acid staining and fluorescence microscopy of thecal/interstitial cells treated with TGFα plus TGFβ1. Further evidence that these cells were undergoing apoptosis came from DNA analysis and the demonstration of DNA laddering. This response of thecal/interstitial cells to TGFα plus TGFβ1 was density dependent; confluent cultures were protected from the induction of apoptosis under these conditions. We conclude that thecal cells are eliminated from atretic follicles by the active and strictly regulated process of apoptosis involving the combined actions of TGFα and TGFβ1. Journal of Endocrinology (1997) 153, 169–178

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Ohshima, K., H. Kishi, M. Itoh, KY Arai, G. Watanabe, K. Arai, K. Uehara, NP Groome, and K. Taya. "Secretory pattern of inhibin A, inhibin B and inhibin pro-alpha C during induced follicular atresia and subsequent follicular development in the golden hamster (Mesocricetus auratus)." Journal of Endocrinology 172, no. 3 (March 1, 2002): 575–81. http://dx.doi.org/10.1677/joe.0.1720575.

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The changes in plasma concentrations of inhibins A, B and pro-alpha C were determined in the cyclic golden hamster during follicular atresia induced with antiserum against luteinizing hormone releasing hormone (LHRH-AS) at 1100 h on day 4 (day 1=day of ovulation). Follicular status in the ovary was also studied by determining the number of follicles ovulating in response to human chorionic gonadotrophin (hCG) injection. The time-courses of changes in plasma concentrations of inhibins A, B and pro-alpha C were different from each other during induced follicular atresia and subsequent follicular development. Plasma concentrations of inhibin A decreased to 58.6% of initial values by 24 h after LHRH-AS treatment, and then remained relatively low until at least 60 h later. Plasma concentrations of inhibin B decreased to 64.2% of the initial values by 18 h after LHRH-AS treatment and remained at basal values for 36 h, but increased abruptly to greater than initial values at 42 h after the treatment. Plasma concentrations of inhibin pro-alpha C increased at 6 and 12 h, decreased suddenly to 21.9% of the initial values by 24 h after LHRH-AS treatment, and then gradually increased until 60 h after LHRH-AS. The number of follicles responding to hCG decreased gradually between 0 and 30 h after LHRH-AS, when no ovulations were observed, and then gradually increased until 60 h. The changes in follicular ovulatory responses to hCG correlated with the plasma profile of inhibin A throughout the experiment. These results suggest that inhibin A is mainly secreted by large antral follicles. In contrast, during the subsequent follicular development, the plasma concentration of inhibin B increased earlier than that of inhibin A. These results suggest that inhibin B is secreted by small and large antral follicles. Plasma concentrations of inhibin pro-alpha C were high at a time when plasma concentrations of oestradiol-17 beta had already decreased, indicating that inhibin pro-alpha C is secreted not only from healthy follicles but also from early atretic antral follicles.

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Rzepkowska, Małgorzata, Dobrochna Adamek-Urbańska, Magdalena Fajkowska, and Marek Łukasz Roszko. "Histological Evaluation of Gonad Impairments in Russian Sturgeon (Acipenser gueldenstaedtii) Reared in Recirculating Aquatic System (RAS)." Animals 10, no. 8 (August 18, 2020): 1439. http://dx.doi.org/10.3390/ani10081439.

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The aim of the study was to raise an issue concerning gonadal impairments in sturgeon reared in recirculating aquatic systems (RAS). In the present study, an in-depth histological evaluation in terms of gonadal pathologies was performed on over-4-year-old (1600 days post-hatching) Russian sturgeon (Acipenser gueldenstaedtii) reared under indoor RAS. A female-biased sex ratio, intersex occurrence, ovarian fat overgrowth, T-cell infiltration and follicle atresia were the most commonly observed disorders in the analyzed gonads. The combined processes of oocyte autophagy and follicular cell apoptosis were engaged in follicular atresia; however, atretic follicles showed a varied morphology, whereas oogonia and oocytes in the early stages of meiosis, as well as spermatogonia, underwent degeneration by apoptosis. The most severe pathology was observed in females with abundant intra-ovarian fat deposition. The extremely fatty ovaries were noted to lose the majority of ovarian follicles, which directly leads to fish sterility. The identified impairments might be related to estrogenic endocrine disruption, as feminization and unspecific vitellogenin synthesis were detected, although the sources of the observed pathologies can be diverse. Therefore, the presented research lays the groundwork for further studies on reproductive disorders in this prized and endangered fish species.

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Ma, Mengnan, Huiming Wang, Yi Zhang, Jinbi Zhang, Jingge Liu, and Zengxiang Pan. "circRNA-Mediated Inhibin–Activin Balance Regulation in Ovarian Granulosa Cell Apoptosis and Follicular Atresia." International Journal of Molecular Sciences 22, no. 17 (August 24, 2021): 9113. http://dx.doi.org/10.3390/ijms22179113.

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Ovarian granulosa cells (GC) play an essential role in the development and atresia of follicles. Emerging studies suggest that non-coding RNAs are involved in the regulation of GC apoptosis. Here, we aimed to analyze the function of ssc-circINHA-001, coded by the first exon of the inhibin subunit α gene (INHA), in resisting GC apoptosis and follicular atresia by enhancing the expression of the inhibin subunit β A (INHBA) through a cluster of miRNAs. A higher expression of ssc-circINHA-001 in healthy follicles compared to early atretic follicles was detected by qRT-PCR. Its circular structure was confirmed by RNase R treatment and reversed PCR. The function of ssc-circINHA-001 in GC resistance to apoptosis was detected by in vitro transfection of its si-RNA. Furthermore, the dual-luciferase reporter assay suggested that ssc-circINHA-001 adsorbed three miRNAs, termed miR-214-5p, miR-7144-3p, and miR-9830-5p, which share the common target INHBA. A low expression of ssc-circINHA-001 increased the levels of the free miRNAs, inhibited INHBA expression, and thus raised GCs apoptosis through a shift from the secretion of activin to that of inhibin. Our study demonstrated the existence of a circRNA–microRNAs–INHBA regulatory axis in follicular GC apoptosis and provides insight into the relationship between circRNA function and its coding gene in inhibin/activin balance and ovarian physiological functions.

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Sinedino, L. D. P., B. T. Gerhardt, J. A. Moura, A. P. Dourado, I. L. Goulart, A. L. R. Rodrigues, J. H. M. Viana, and L. A. G. Nogueira. "16 STRATEGIES OF FOLLICULAR WAVE SYNCHRONIZATION WITH ESTRADIOL BENZOATE IN GYR (BOS TAURUS INDICUS) CATTLE." Reproduction, Fertility and Development 25, no. 1 (2013): 155. http://dx.doi.org/10.1071/rdv25n1ab16.

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Physiological and behavioral differences between Bos taurus and Bos indicus can influence the response to a fixed AI protocol. The objective of this study was to examine the reduction of the usual dose of 2 mg of estradiol benzoate (EB) to 1 mg at the beginning of a fixed-time AI protocol, aiming at follicular regression. In a second step, we evaluated the effect of EB on follicle development during follicular pre-deviation and dominance. The experiment was performed at Monte Verde Farm (Uberaba, MG, Brazil). Twenty-two cows (n = 10 heifers and n = 12 nonlactating cows) underwent an estrous synchronization protocol with a progesterone-releasing intravaginal device (P4; Sincrogest®, Ouro Fino Animal Health, São Paulo, Brazil) and received 1 (G1mg, n = 11) or 2 mg (G2mg, n = 11) of EB (Sincrodiol®, Ouro Fino Animal Health), on a random day (designated Day 0). Follicular dynamics was monitored once per day by ultrasonography from Day 0 to 4 with blood sample collections. In a second step, females received 2 mg of EB on Day 3 (GD3, pre-deviation, n = 4) or Day 5 (GD5, dominance, n = 4) of the estrous cycle (Day 0 was the ovulation). Following these treatments, follicular development was monitored daily for 6 days with blood sample collections. The statistical analysis was conducted using the SAS System for Windows 2 (2003; SAS Institute Inc., Cary, NC, USA). The explanatory variables included in the statistical model were the dose of EB, animal category (cows and heifers), and their interaction. The mean test was used to compare intervals from EB treatment to follicular atresia and follicular wave emergence using ANOVA. Progesterone concentrations between groups were compared using the Wilcoxon test. Independently of animal category or stage of the estrous cycle, both EB doses (1 or 2 mg) induced follicular atresia in 2.2 ± 0.9 and 2.1 ± 1.2 days (P > 0.05), respectively. Emergence of a new follicular wave was observed, from Day 0 to 4, in 64% (7/11) of females from G1mg and in 45% (5/11) from G2mg, and the interval between treatment and follicular emergence was 3.4 ± 0.8 and 3.0 ± 1.0 days (P > 0.05), respectively. Plasma progesterone concentrations of the 22 animals increased from 2.1 ± 2.0 ng mL–1 to 7.6 ± 3.0 ng mL–1 by 24 h after the device insertion (P < 0.05), reaching peak concentration (8.0 ± 3.0 ng mL–1) by 48 h after treatment beginning, decreasing to 6.4 ± 2.5 ng mL–1 by 72 h, and remaining constant up to 96 h. Estradiol benzoate injection at follicle pre-deviation (GD3) caused follicular atresia (2.0 ± 1.4 days) and emergence of a new follicular wave in 3.7 ± 0.1 days in all animals (4/4). However, EB injection during follicle dominance (GD5) did not synchronize a new follicular wave and follicles persisted during the time of monitoring. Furthermore, EB applied at dominance hastened luteolysis in 50% (2/4) of the treated animals. In conclusion, a reduced dose of EB (1 mg) at the beginning of the protocol with P4 effectively induces follicular atresia. To synchronize a wave emergence at any stage of the estrous cycle, EB must be associated with an exogenous source of progesterone.

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da Silva Bitecourt, Frederico, Carina Oliveira Dumont Horta, Karen Santos Lima, Bruno Bastos Godoi, Fernanda Luiza Menezes Bello, Cíntia Maria Rodrigues, Luana Pereira Leite Schetino, and Kinulpe Honorato-Sampaio. "Morphological study of apoptosis in granulosa cells and ovulation in a model of atresia in rat preovulatory follicles." Zygote 26, no. 4 (August 2018): 336–41. http://dx.doi.org/10.1017/s0967199418000291.

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SummaryPrevious studies have established a model of atresia in preovulatory follicles after stimulation of immature rats with equine chorionic gonadotropin (eCG). This gonadotropin recruits a follicular pool and the deprivation of preovulatory luteinizing hormone (LH) surge induces the atresia in preovulatory follicles. The present study investigated the occurrence of ovulation and provided some morphological features of granulosa cell (GC) apoptosis of atretic follicles at 0, 48, 72 and 120 h after eCG stimulation. Histological sections of ovaries from untreated animals (0 h) showed primordial, primary, secondary and early antral follicles. After 48 h ovaries showed large antral follicles. Preovulatory follicles were observed at 72 h, and two out of five rats displayed cumulus–oocyte complexes (COCs) in the oviducts. All animals exhibited corpora lutea after 120 h. We observed increased estradiol (E2) levels 48 h after eCG treatment that might trigger an endogenous preovulatory gonadotropin surge. Higher progesterone (P4) level, which is the hallmark of a functional corpus luteum, was observed at 120 h. Atresia in secondary and antral follicles was observed by pyknotic granulosa cell nuclei in histology and positive immunolabelling for cleaved caspase 3. We also observed macrophages in secondary and antral follicles in atresia. Transmission electron microscopy revealed GCs with compacted chromatin against the nuclear envelope, nuclear fragmentation, cell shrinkage and fragmentation. No preovulatory follicles showed apoptosis of GCs. In conclusion, our results suggested the occurrence of an endogenous gonadotropin surge, promoting ovulation and preventing atresia of preovulatory follicles.

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Velasquez, Ethel V., Mariana Ríos, María Elena Ortiz, Carlos Lizama, Elizabeth Nuñez, Dalhia Abramovich, Felipe Orge, et al. "Concanavalin-A Induces Granulosa Cell Death and Inhibits FSH-Mediated Follicular Growth and Ovarian Maturation in Female Rats." Endocrinology 154, no. 5 (March 20, 2013): 1885–96. http://dx.doi.org/10.1210/en.2012-1945.

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Abstract Reproductive success stems from a finely regulated balance between follicular maturation and atresia, in which the role of carbohydrate structure is poorly understood. Here, we describe for the first time a fraction of purified recombinant human FSH that is capable of bringing about the cell death of granulosa cells and preventing follicular maturation in a rat model. Further analysis by mass spectrometry revealed the presence of the lectin Concanavalin-A (Con-A) within this fraction of recombinant FSH. Using both the fractionated FSH and Con-A, the observed cell death was predominantly located to the granulosa cells. Ex vivo culture of rat follicles demonstrated that follicle degeneration occurred and resulted in the release of a denuded and deteriorated oocyte. Moreover, in vivo experiments confirmed an increase in atresia and a corresponding reduction confined to follicle in early antral stage. As a mechanism of action, Con-A reduces ovarian proliferation, Von Willebrand staining, and angiogenesis. Based on the observation that Con-A may induce granulosa cell death followed by follicle death, our results further demonstrate that follicular carbohydrate moiety is changing under the influence of FSH, which may allow a carbohydrate-binding lectin to increase granulosa cell death. The physiological consequences of circulating lectin-like molecules remain to be determined. However, our results suggest a potential exploitation of carbohydrate binding in fertility and ovarian cancer treatment. This work may shed light on a key role of carbohydrates in the still obscure physiological process of follicular selection and atresia.

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Burke, Christopher R., Horacio Cárdenas, Martin L. Mussard, and Michael L. Day. "Histological and steroidogenic changes in dominant ovarian follicles during oestradiol-induced atresia in heifers." Reproduction 129, no. 5 (May 2005): 611–20. http://dx.doi.org/10.1530/rep.1.00384.

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Histological and steroidogenic changes within dominant ovarian follicles (DFs) undergoing atresia following systemic administration of oestradiol benzoate (ODB) were characterized in beef heifers. At 5.6 ± 0.1 days after the onset of oestrus, heifers received 1 mg ODB i.m./500 kg body weight (ODB; n = 15) or served as controls (n = 15). Timing of treatment initiation was designated as hour (h) 0 on day (d) 0, and coincided with the presence of the DF of the first follicular wave (DF1). Within treatments, the DF1 was collected following ovariectomy in four animals at h 12, h 36 or after ultrasonic detection of a new wave (NW) of ovarian follicular development. In heifers of the NW groups (n = 7 per treatment), blood samples were collected at intervals of 20 min for 12 h beginning at h − 12, 0, 24 and 48 to characterize circulating LH patterns. Administration of ODB suppressed (P < 0.01) mean concentrations of LH at h 24 and h 48 by preventing (P < 0.05) the increase in LH pulse amplitude observed in controls, but had no effect on FSH. Follicular fluid (FF) concentrations of androgens and oestradiol were reduced at h 36 in the ODB-treated group. The diameter of the DF1 and the number of granulosa cell layers were also reduced in ODB-treated as compared with control heifers. Treatment differences were not observed in the proportion of apoptotic granulosa cells as assessed using the TUNEL assay method, and timing of a new wave of follicular development (d 4.6 ± 0.2) was similar (P > 0.1) among treatments. A prominent characteristic of oestradiol-induced atresia of the DF1 of the oestrous cycle in heifers was a loss in oestrogenic function associated with reduced LH support. However, the timing of new follicular development may be influenced by a factor(s) other than the status of the DF undergoing oestradiol-induced atresia.

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Greenfeld, Chuck R., Janice K. Babus, Priscilla A. Furth, Sam Marion, Patricia B. Hoyer, and Jodi A. Flaws. "BAX is involved in regulating follicular growth, but is dispensable for follicle atresia in adult mouse ovaries." Reproduction 133, no. 1 (January 2007): 107–16. http://dx.doi.org/10.1530/rep-06-0144.

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Mammalian females are endowed with a finite number of primordial follicles at birth or shortly thereafter. Immediately following the formation of the primordial follicle pool, cohorts of these follicles are recruited to begin growth, and this recruitment continues until the primordial follicle population is depleted. Once recruited, a follicle will either grow and ovulate or undergo atresia. Follicle atresia results from the apoptotic death of follicular cells. Members of the BCL-2 family of proteins are important regulators of apoptosis in most cells including in the ovary. Here, we tested the hypothesis that the proapoptotic BAX is an important regulator of follicle survival. We used a variety of histological and biochemical techniques to investigate the impact ofBaxdeletion on follicle growth and death. We observed that theBaxdeletion results in delayed vaginal opening and altered follicular growth. Young adultBax-deficient ovaries contained increased numbers of primordial follicles and a trend towards reduced numbers of growing follicles.Baxdeficiency led to a reduction in average litter size, and also a reduction in the number of oocytes ovulated in response to exogenous gonadotropins. In contrast,Baxdeficiency did not alter follicle atresia. In conclusion, BAX appears to be an important regulator of follicle growth, but is dispensable for follicle atresia in mice.

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Dubinina, Anna Yu, and Alexander O. Zolotov. "Atresia of oocytes for northern rock sole Lepidopsetta polyxystra (Pleuronectiformes, Pleuronectidae) from the Pacific waters of Kamchatka." Izvestiya TINRO 180, no. 1 (March 30, 2015): 99–106. http://dx.doi.org/10.26428/1606-9919-2015-180-99-106.

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Northern rock sole is abundant and important for fishery species in the Pacific waters of Kamchatka and northern Kuril Islands. Sometimes its oogenesis occurs with the oocytes atresia. By the data of the females reproductive tissue investigation conducted in 2011-2012, the degeneration appears for the late perinucleus (II and II-III maturing stages), vitellogene cells (III and IV stages), and ovarian follicles (stages VI-III) and develops by three principally different ways. Comparing with other fish species, atresia of the late perinucleus of northern rock sole realizes without follicular epithelium and affects either 15 % of these cells (for 8 % of juveniles) or 67 % of these cells (for 4 % of non-spawning adults). In the process of the vitellogene oocytes atresia, a symplast forms between follicular epithelium and chorion and conserves until final resorption of the oocyte. The cortical alveoli and vacuolated cells are damaged more often (5.6 %) than the oocytes with advanced yolk (2.4 %). Resorption of ovarian follicles by stroma connective tissue of oviparous plates is typical for all postspawning females, their portion doesn’t exceed 3 % of cells in each generation. Obviously, atresia of vitellogene oocytes reduces the fish fecundity, therefore the total and population fecundity is forming until the stage IV.

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Derecka, K., H. Kalamarz, and AJ Ziecik. "Does Apoptosis Occur during Follicular Atresia in the Follicular Walls of the Porcine Ovary?" Reproduction in Domestic Animals 30, no. 1 (February 1995): 32–35. http://dx.doi.org/10.1111/j.1439-0531.1995.tb01173.x.

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Journal articles on the topic 'Follicular atresia'

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