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Journal articles on the topic 'Cervix uteri Gene expression'

Author: Grafiati

Published: 4 June 2021

Last updated: 7 February 2022

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1

Kwon, Kyung Ik, Tae Sung Lee, Jiung Ho Rhee, Soon Do Cha, Sang Sook Lee, and Young Wook Suh. "Expression of the mutant p53 gene in the carcinoma of the cervix uteri." Korean Journal of Gynecologic Oncology and Colposcopy 5, no. 4 (1994): 23. http://dx.doi.org/10.3802/kjgoc.1994.5.4.23.

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2

Miller, C., and D. A. Sassoon. "Wnt-7a maintains appropriate uterine patterning during the development of the mouse female reproductive tract." Development 125, no. 16 (August 15, 1998): 3201–11. http://dx.doi.org/10.1242/dev.125.16.3201.

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The murine female reproductive tract differentiates along the anteroposterior axis during postnatal development. This process is marked by the emergence of distinct cell types in the oviduct, uterus, cervix and vagina and is dependent upon specific mesenchymal-epithelial interactions as demonstrated by earlier heterografting experiments. Members of the Wnt family of signaling molecules have been recently identified in this system and an early functional role in reproductive tract development has been demonstrated. Mice were generated using ES-mediated homologous recombination for the Wnt-7a gene (Parr, B. A. and McMahon, A. P. (1995) Nature 374, 350–353). Since Wnt-7a is expressed in the female reproductive tract, we examined the developmental consequences of lack of Wnt-7a in the female reproductive tract. We observe that the oviduct lacks a clear demarcation from the anterior uterus, and acquires several cellular and molecular characteristics of the uterine horn. The uterus acquires cellular and molecular characteristics that represent an intermediate state between normal uterus and vagina. Normal vaginas have stratified epithelium and normal uteri have simple columnar epithelium, however, mutant uteri have stratified epithelium. Additionally, Wnt-7a mutant uteri do not form glands. The changes observed in the oviduct and uterus are accompanied by a postnatal loss of hoxa-10 and hoxa-11 expression, revealing that Wnt-7a is not required for early hoxa gene expression, but is required for maintenance of expression. These clustered hox genes have been shown to play a role in anteroposterior patterning in the female reproductive tract. In addition to this global posterior shift in the female reproductive tract, we note that the uterine smooth muscle is disorganized, indicating development along the radial axis is affected. Changes in the boundaries and levels of other Wnt genes are detectable at birth, prior to changes in morphologies. These results suggest that a mechanism whereby Wnt-7a signaling from the epithelium maintains the molecular and morphological boundaries of distinct cellular populations along the anteroposterior and radial axes of the female reproductive tract.

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3

Riethdorf, Sabine, Lutz Riethdorf, Nicole Richter, and Thomas Löning. "Expression of the MCP-1 Gene and the HPV 16 E6/E7 Oncogenes in Squamous Cell Carcinomas of the Cervix uteri and Metastases." Pathobiology 66, no. 6 (1998): 260–67. http://dx.doi.org/10.1159/000028032.

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4

Alvarez-Rodriguez, Manuel, Mohammad Atikuzzaman, Heli Venhoranta, Dominic Wright, and Heriberto Rodriguez-Martinez. "Expression of Immune Regulatory Genes in the Porcine Internal Genital Tract Is Differentially Triggered by Spermatozoa and Seminal Plasma." International Journal of Molecular Sciences 20, no. 3 (January 25, 2019): 513. http://dx.doi.org/10.3390/ijms20030513.

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Mating or cervical deposition of spermatozoa or seminal plasma (SP) modifies the expression of genes affecting local immune defense processes at the oviductal sperm reservoir in animals with internal fertilization, frequently by down-regulation. Such responses may occur alongside sperm transport to or even beyond the reservoir. Here, immune-related gene expression was explored with cDNA microarrays on porcine cervix-to-infundibulum tissues, pre-/peri-ovulation. Samples were collected 24 h post-mating or cervical deposition of sperm-peak spermatozoa or SP (from the sperm-peak fraction or the whole ejaculate). All treatments of this interventional study affected gene expression. The concerted action of spermatozoa and SP down-regulated chemokine and cytokine (P00031), interferon-gamma signaling (P00035), and JAK/STAT (P00038) pathways in segments up to the sperm reservoir (utero-tubal junction (UTJ)/isthmus). Spermatozoa in the vanguard sperm-peak fraction (P1-AI), uniquely displayed an up-regulatory effect on these pathways in the ampulla and infundibulum. Sperm-free SP, on the other hand, did not lead to major effects on gene expression, despite the clinical notion that SP mitigates reactivity by the female immune system after mating or artificial insemination.

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5

Goldberg, D. M., and E. P. Diamandis. "Models of neoplasia and their diagnostic implications: a historical perspective." Clinical Chemistry 39, no. 11 (November 1, 1993): 2360–74. http://dx.doi.org/10.1093/clinchem/39.11.2360.

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Abstract In comparison with normal cells, cancer cells have an enhanced ability to trap both nitrogen and energy; an enhanced operation of the glycolytic and direct oxidative pathways, leading to accumulation of lactate and increased production of NADPH; and a greater content of lysosomal hydrolases. These changes represent a reprogramming of gene expression, which, at its most specific, is accompanied by the reappearance in the cell and ultimately in the body fluids of oncodevelopmental proteins not normally found in mature adult tissues. The most florid stage of this reprogramming leads to the metastatic phenotype, which confers upon the cancer cell the ability to stimulate angiogenesis, invade the bloodstream and lymphatic vessel, and arrest and proliferate in distant tissues. The diagnostic implications of these phenotypic changes are illustrated for cancer of the cervix uteri and cancer of the colon. We also review the classical theories of neoplasia, including the cellular anoxia concept of Warburg, the deletion hypothesis of Potter, and various other mechanisms emphasizing genomic derepression and impaired immunity. The critical steps in chemical carcinogenesis are described, and the Vogelstein-Lane model is presented, emphasizing the stepwise and cumulative genomic changes affecting chromosomes 5q, 17p, 18q, and gene amplification of chromosome 12 as well as genomic instability resulting from reduced DNA methylation. The main consequences of these genomic alterations include overexpression or activation of oncogenes such as c-myc and k-ras, together with mutation or functional inactivation of suppressor genes such as p53. Finally, the implications of these findings for diagnosis and management are illustrated by reference to recent investigations in cancers of the breast, colon, and bladder, in which these genomic alterations can be detected by examination of appropriate cellular material and by detection in serum of antibodies to the p53 gene product.

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6

Alvarez-Rodriguez, Manuel, Cristina A. Martinez, Dominic Wright, and Heriberto Rodriguez-Martinez. "Does the Act of Copulation per se, without Considering Seminal Deposition, Change the Expression of Genes in the Porcine Female Genital Tract?" International Journal of Molecular Sciences 21, no. 15 (July 31, 2020): 5477. http://dx.doi.org/10.3390/ijms21155477.

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Semen—through its specific sperm and seminal plasma (SP) constituents—induces changes of gene expression in the internal genital tract of pigs, particularly in the functional sperm reservoir at the utero-tubal junction (UTJ). Although seminal effects are similarly elicited by artificial insemination (AI), major changes in gene expression are registered after natural mating, a fact suggesting the act of copulation induces per se changes in genes that AI does not affect. The present study explored which pathways were solely influenced by copulation, affecting the differential expression of genes (DEGs) of the pre/peri-ovulatory genital tract (cervix, distal uterus, proximal uterus and UTJ) of estrus sows, 24 h after various procedures were performed to compare natural mating with AI of semen (control 1), sperm-free SP harvested from the sperm-peak fraction (control 2), sperm-free SP harvested from the whole ejaculate (control 3) or saline-extender BTS (control 4), using a microarray chip (GeneChip® porcine gene 1.0 st array). Genes related to neuroendocrine responses (ADRA1, ADRA2, GABRB2, CACNB2), smooth muscle contractility (WNT7A), angiogenesis and vascular remodeling (poFUT1, NTN4) were, among others, overrepresented with distal and proximal uterine segments exhibiting the highest number of DEGs. The findings provide novel evidence that relevant transcriptomic changes in the porcine female reproductive tract occur in direct response to the specific act of copulation, being semen-independent.

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7

Yi, B. R., S. U. Kim, and K. C. Choi. "126 POTENTIAL EFFECTS OF ENGINEERED STEM CELLS TRANSDUCED WITH THERAPEUTIC GENES AGAINST HeLa HUMAN CERVICAL CANCER CELLS VIA A SELECTIVE TUMOR TROPISM CAUSED BY VASCULAR ENDOTHELIAL GROWTH FACTOR." Reproduction, Fertility and Development 26, no. 1 (2014): 177. http://dx.doi.org/10.1071/rdv26n1ab126.

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According to the World Health Organization, cancer of cervix uteri is the second most common cancer among women worldwide. Recently, cervical cancer still remains a significant public health problem for women despite the development of the human papilloma virus vaccine. The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTEC) expressing bacterial cytosine deaminase (CD), human interferon-β (IFN-b) gene, or both against HeLa human cervical cancer and the migration factors of the GESTEC toward the cancer cells. A continuously dividing immortalized cell line of neural stem cells (NSC) from a single clone of human fetal brain, HB1.F3, was developed by introducing v-myc. The further introduction of these NSC with bacterial CD and human IFN-b resulted in the generation of HB1.F3.CD and HB1.F3.CD.IFN-b cells. The anticancer effect of these GESTEC was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed to assess the migration capability of the stem cells to cervical cancer cells. Next, several chemoattractant ligands and their receptors related to a selective migration of the stem cells towards HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by the CD gene and it caused the cell death in a co-culture system. When IFN-b was additionally expressed with the CD gene by these GESTEC, the anticancer activity was significantly increased. In the migration assay, the GESTEC selectively migrated to HeLa cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GESTEC. These GESTEC transduced with the CD gene and IFN-b may provide the potential of a novel gene therapy for anti-cervical cancer treatments via their selective tumour tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTEC. This work was supported by a grant from the Next-Generation BioGreen 21 Program (No. PJ009599), Rural Development Administration, Republic of Korea.

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8

IWAHASHI, MASAAKI, and YASUTERU MURAGAKI. "Decreased type III collagen expression in human uterine cervix of prolapse uteri." Experimental and Therapeutic Medicine 2, no. 2 (2011): 271–74. http://dx.doi.org/10.3892/etm.2011.204.

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9

Negri, Giovanni, Fabio Vittadello, Fabio Romano, Armin Kasal, Francesco Rivasi, Salvatore Girlando, Christine Mian, and Eduard Egarter-Vigl. "P16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri." Virchows Archiv 445, no. 6 (October 9, 2004): 616–20. http://dx.doi.org/10.1007/s00428-004-1127-9.

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10

Randall, G. W., J. C. Daniel, and B. S. Chilton. "Prolactin enhances uteroglobin gene expression by uteri of immature rabbits." Reproduction 91, no. 1 (January 1, 1991): 249–57. http://dx.doi.org/10.1530/jrf.0.0910249.

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11

Kupryjańczyk, Jolanta. "Epidermal Growth Factor Receptor Expression in the Normal and Inflamed Cervix Uteri: A Comparison with Estrogen Receptor Expression." International Journal of Gynecological Pathology 9, no. 3 (July 1990): 263–71. http://dx.doi.org/10.1097/00004347-199007000-00006.

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12

Timoshenko, O. S., T. A. Gureeva, E. V. Kugaevskaya, L. E. Zavalishina, Yu Yu Andreeva, and N. I. Solovyeva. "The expression of EMMPRIN and the matrix metalloproteinase MMP-1 in the cervix uteri and corpus uteri in cervical squamous cell carcinoma." Arkhiv patologii 81, no. 6 (2019): 34. http://dx.doi.org/10.17116/patol20198106134.

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13

Riethdorf, L., J. T. O'Connell, S. Riethdorf, A. Cviko, and C. P. Crum. "Differential expression of MUC2 and MUC5AC in benign and malignant glandular lesions of the cervix uteri." Virchows Archiv 437, no. 4 (October 19, 2000): 365–71. http://dx.doi.org/10.1007/s004280000273.

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14

Lebedeva, Olga Petrovna, Olesya Nikolaevna Ivashova, Sergey Petrovich Pakhomov, Mikhail Ivanovich Churnosov, Nataliya Ivanovna Samborskaya, and Elena Anatolevna Fedorenko. "Expression of antimicrobial peptides in the epithelium of the cervix uteri after caesarian section and vaginal birth." Journal of obstetrics and women's diseases 63, no. 5 (December 15, 2014): 58–63. http://dx.doi.org/10.17816/jowd63558-63.

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The Background: Antimicrobial peptides are first line of defense for mucosa against viruses, bacteria, protozoa and fungi. Meanwhile, expression of antimicrobial peptides in postpartum period has not been studied. Objective: To estimate the expression of mRNA of antimicrobial peptides in epithelium of the cervix uteri after caesarean section and vaginal birth 3 or 4 days after delivery. Materials and methods: The data-sample consisted of 17 women after caesarean section and 46 women after vaginal delivery examined on days 3 or 4 of postpartum period. Quantitative reverse transcription PCR method was used to study mRNA expression of antimicrobial peptides. Statistical analysis was performed using Mann-Whitney criteria. Results: It was shown that higher level of expression of SLPI, HNP3, HD6 and HBD4 in the endocervix was present in women who delivered via caesarean section compared with those who had vaginal delivery. Conclusion: Women who underwent caesarean section exhibited increased expression of antimicrobial peptides compared to those who had vaginal birth. This increased expression can be attributed to multiple reasons such as differences in vaginal microflora restoration, different changes in hormone levels and also due to surgical trauma after operative delivery. The use of antimicrobial peptides can give new opportunities for prophylaxis and treatment of septic complications that occur in postpartum period.

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15

Kang, Han-Seung, Chae-Kwan Lee, Ju-Ran Kim, Seong-Jin Yu, Sung-Goo Kang, Deog-Hwan Moon, Chang-Hee Lee, and Dong-Kyoo Kim. "Gene expression analysis of the pro-oestrous-stage rat uterus reveals neuroligin 2 as a novel steroid-regulated gene." Reproduction, Fertility and Development 16, no. 8 (2004): 763. http://dx.doi.org/10.1071/rd04040.

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In the present study, differential gene expression in the uteri of ovariectomised (OVX) and pro-oestrous rats (OVX v. pro-oestrus pair) was investigated using cDNA expression array analysis. Differential uterine gene expression in OVX rats and progesterone (P4)-injected OVX rats (OVX v. OVX + P4 pair) was also examined. The uterine gene expression profiles of these two sets of animals were also compared for the effects of P4 treatment. RNA samples were extracted from uterine tissues and reverse transcribed in the presence of [α32P]-dATP. Membrane sets of rat arrays were hybridised with cDNA probe sets. Northern blot analysis was used to validate the relative gene expression patterns obtained from the cDNA array. Of the 1176 cDNAs examined, 23 genes showed significant (>two-fold) changes in expression in the OVX v. pro-oestrus pair. Twenty of these genes were upregulated during pro-oestrus compared with their expression in the OVX rat uterus. In the OVX v. OVX + P4 pair, 22 genes showed significant (>two-fold) changes in gene expression. Twenty of these genes were upregulated in the OVX + P4 animals. The genes for nuclear factor I–XI, afadin, neuroligin 2, semaphorin Z, calpain 4, cyclase-associated protein homologue, thymosin β-4X and p8 were significantly upregulated in the uteri of the pro-oestrus and OVX + P4 rats of both experimental pairs compared with the OVX rat uteri. These genes appear to be under the control of P4. One of the most interesting findings of the present study is the unexpected and marked expression of the neuroligin 2 gene in the rat uterus. This gene is expressed at high levels in the central nervous system and acts as a nerve cell adhesion factor. According to Northern blot analysis, neuroligin 2 gene expression was higher during the pro-oestrus and metoestrus stages than during the oestrus and dioestrus stages of the oestrous cycle. In addition, neuroligin 2 mRNA levels were increased by both 17β-oestradiol (E2) and P4, although P4 administration upregulated gene expression to a greater extent than injection of E2. These results indicate that neuroligin 2 gene expression in the rat uterus is under the control of both E2 and P4, which are secreted periodically during the oestrous cycle.

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16

Sarmadi, Soheila, Narges Izadi-mood, Mojdeh Pourlashkari, Fariba Yarandi, and Sanaz Sanii. "HPV L1 capsid protein expression in squamous intraepithelial lesions of cervix uteri and its relevance to disease outcome." Archives of Gynecology and Obstetrics 285, no. 3 (July 26, 2011): 779–84. http://dx.doi.org/10.1007/s00404-011-2010-y.

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17

Rodríguez-Alvarez, Lleretny, José Cox, Felipe Navarrete, Cristián Valdés, Teresa Zamorano, Ralf Einspanier, and Fidel Ovidio Castro. "Elongation and gene expression in bovine cloned embryos transferred to temporary recipients." Zygote 17, no. 4 (June 8, 2009): 353–65. http://dx.doi.org/10.1017/s0967199409005486.

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SummaryElongated embryos provide a unique source of information about trophoblastic differentiation, gene expression and maternal-embryonic interactions; however they are difficult and costly to obtain, especially elongated cloned embryos. One alternative is their production in heterologous temporary recipients such as sheep and goats. We aimed to produce elongated bovine cloned embryos using heterologous transfer to temporary recipients. Day-7 cloned cattle blastocysts were transferred to the uteri of ewes and goats and recovered as elongated structures at day 17. We evaluated elongation, length, presence of embryonic disc and expression of several important genes for embryonic development. We also produced homologous (cloned cattle embryos transferred into cattle uteri). Cloned bovine blastocysts were able to proceed with preimplantation development through elongation with high efficiency despite the species to which they were transferred. In qualitative and quantitative RT-PCR experiments we found differences in the pattern of gene expression among embryos recovered from different species. Sox2, Nanog and FGF-4 were markedly deregulated. No previous reports about the expression pattern of the studied genes had been published for elongated bovine cloned embryos produced in intermediate recipients, furthermore, the pattern of expression of Nanog, Oct4, Eomes, Cdx2, IFN-tau, Dicer, FGF-4 and Sox2 shown here are novel for elongated cloned bovine embryos created by hand-made cloning. Our data confirmed that sheep and goats can be used as temporary recipients. This model could serve as a basis for further research on gene expression and cellular changes during bovine peri-implantation development.

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18

Jia, Yanni, Rui Cai, Tong Yu, Ruixue Zhang, Shouqin Liu, XinYan Guo, Chunmei Shang, Aihua Wang, Yaping Jin, and Pengfei Lin. "Progesterone-induced RNA Hand2os1 regulates decidualization in mice uteri." Reproduction 159, no. 3 (March 2020): 303–14. http://dx.doi.org/10.1530/rep-19-0401.

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Decidualization is a critical process for successful embryo implantation and subsequent placenta formation. The characterization and physiological function of lncRNA during decidualization remain largely unknown. In the present study, we conducted RNA-sequencing analysis to compare gene expression between decidua of days 6 and 8, and normal pregnant endometrium (day 4). A total of 2332 high-confidence putative lncRNA transcripts were expressed. Functional clustering analysis of cis and trans lncRNA targets showed that differentially expressed lncRNAs may regulate multiple gene ontology terms and pathways that have important functions in decidualization. Subsequent analyses using qRT-PCR validated that eight of all lncRNAs were differentially regulated in mice uteri during decidualization, both in vivo and in vitro. Furthermore, we showed that differentially expressed lncRNA of Hand2os1 was specifically detected in stromal cells on days 2 to 5 of pregnancy and was strongly upregulated in decidual cells on days 6–8 of pregnancy. Similarly, Hand2os1 expression was also strongly expressed in decidualized cells following artificial decidualization, both in vivo and in vitro. In uterine stromal cells, P4 was able to significantly upregulate the expression of Hand2os1, but upregulation was impeded by RU486, whereas E2 appeared to have no regulating effect on Hand2os1 expression. Concurrently, Hand2os1 significantly promoted the decidual process in vitro and dramatically increased decidualization markers Prl8a2 and Prl3c1. Our results provide a valuable catalog for better understanding of the functional roles of lncRNAs in pregnant mouse uteri, as it relates to decidualization.

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19

Xia, Hong-Fei, Jing-Li Cao, Xiao-Hua Jin, and Xu Ma. "MiR199a is implicated in embryo implantation by regulating Grb10 in rat." REPRODUCTION 147, no. 1 (January 2014): 91–99. http://dx.doi.org/10.1530/rep-13-0290.

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MiR199a was found to be differentially expressed in rat uteri between the prereceptive and receptive phase via microRNA (miRNA) microarray analysis in our previous study. However, the role of miR199a in rat embryo implantation remained unknown. In the study, northern blot results showed that the expression levels of miR199a were higher on gestation days 5 and 6 (g.d.5–6) in rat uteri than on g.d.3–4 and g.d.7–8. In situ localization of miR199a in rat uteri showed that miR199a was mainly localized in the stroma or decidua. The expression of miR199a was not significantly different in the uteri of pseudopregnant rats and evidently increased in the uteri of rats subjected to activation of delayed implantation and experimentally induced decidualization. Treatment with 17β-estradiol or both 17β-estradiol and progesterone significantly diminished miR199a levels. Gain of function of miR199a in endometrial stromal cells isolated from rat uteri inhibited cell proliferation and promoted cell apoptosis. Loss of function of miR199a displayed opposite roles on cell proliferation and apoptosis. Further investigation uncovered a significant inverse association between the expression of miR199a and growth factor receptor-bound protein 10 (Grb10), an imprinted gene, and miR199a could bind to the 3′UTR of Grb10 to inhibit Grb10 translation. In addition, in vivo analysis found that the immunostaining of GRB10 was attenuated in the stroma or decidua from g.d.4 to 6, contrary to the enhancement of miR199a. Collectively, upregulation of miR199a in rat uterus during the receptive phase is regulated by blastocyst activation and uterine decidualization. Enforced miR199a expression suppresses cell proliferation partially through targeting Grb10.

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20

Lukovic, J., K. Han, M. Pintilie, N. Chaudary, R. Hill, A. Fyles, and M. Milosevic. "OC-0149: Intratumoral heterogeneity and hypoxia gene expression signatures in cervix cancer." Radiotherapy and Oncology 127 (April 2018): S75. http://dx.doi.org/10.1016/s0167-8140(18)30459-6.

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21

Yamada, N., Y. Makino, R. A. Clark, D. W. Pearson, M. G. Mattei, J. L. Guénet, E. Ohama, et al. "Human inositol 1,4,5-trisphosphate type-1 receptor, InsP3R1: structure, function, regulation of expression and chromosomal localization." Biochemical Journal 302, no. 3 (September 15, 1994): 781–90. http://dx.doi.org/10.1042/bj3020781.

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We have isolated cDNA clones encoding an inositol 1,4,5-trisphosphate receptor type 1 (InsP3R1) from human uteri and a leukaemic cell line, HL-60. Northern-blot analysis showed that approx. 10 kb of InsP3R1 mRNA is expressed in human uteri, oviducts and HL-60 cells. The predicted amino acid sequence of human InsP3R1 (2695 amino acids) has 99% identity with that of the mouse SI-/SII- splicing counterpart. Western-blot analysis with anti-(mouse InsP3R1) antibodies showed that InsP3R1 protein of human uteri and oviducts of approx 220 kDa is immunostained. Northern-blot analysis of HL-60 cell differentiation along the neutrophilic lineage induced by retinoic acid or dimethylsulphoxide showed an accompanying enhanced expression of InsP3R1 mRNA. Immunohistochemical analysis of the cerebella of spinocerebellar degeneration patients showed a variable loss of Purkinje cells with an altered pattern of immunostaining. The InsP3R1 gene (Insp3r1) was localized to the 3P25-26 region of human chromosome 3. The data presented here clearly show that InsP3R1 exists widely in human tissues and may play critical roles in various kinds of cellular functions.

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22

Rollason, T. P., P. Byrne, A. Williams, and G. Brown. "Expression of epithelial membrane and 3-fucosyl-N-acetyllactosamine antigens in cervix uteri with particular reference to adenocarcinoma in situ." Journal of Clinical Pathology 41, no. 5 (May 1, 1988): 547–52. http://dx.doi.org/10.1136/jcp.41.5.547.

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23

Park, Hyun Jung, In Sun Kuk, Jin Hoi Kim, Jae Hwan Kim, Sang Jin Song, Bum Chae Choi, Bokyoung Kim, Nam Hyung Kim, and Hyuk Song. "Characterisation of mouse interferon-induced transmembrane protein-1 gene expression in the mouse uterus during the oestrous cycle and pregnancy." Reproduction, Fertility and Development 23, no. 6 (2011): 798. http://dx.doi.org/10.1071/rd10086.

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During the oestrous cycle, pregnancy and parturition, the uterus undergoes marked morphological, physiological and functional changes. Amid these changes, the Wnt/β-catenin signalling pathway has been identified as having a crucial role in regulating associated biological events. Recently, based on results from a mouse embryo study, interferon-induced transmembrane protein 1 (Ifitm1) was reported as a downstream molecule of the Wnt/β-catenin signalling pathway. Differential expression patterns of the Ifitm1 gene during the oestrous cycle, pregnancy and parturition were identified in the present study. Quantitative real-time polymerase chain reaction data from uterine samples of mice induced start the oestrous cycle by injection of human chorionic gonadotropin (hCG) and revealed that Ifitm1 mRNA expression increased from late pro-oestrus to metoestrus, and decreased during dioestrus and early pro-oestrus. During pregnancy, Ifitm1 gene expression was minimal until parturition, but increased markedly 2 days after parturition. This significant elevation in Ifitm1 gene expression at post partum stage was identical to Ifitm1 expression after the induction of abortion by injection of prostaglandin F2α. Interestingly, pregnant mare serum gonadotropin (PMSG) and oestrogen are also facilitates changes in Ifitm1 gene expression in an ovariectomised (OVX) mouse model. Expression of Ifitm1 mRNA was higher in response to PMSG than other hormones investigated. These results suggest that Ifitm1 may be involved in uteri physiology, although the mechanisms involved in the regulation of this gene expression and function in the uterus remain unknown. In the present study, differential expression patterns of the Ifitm1 gene were identified in the uteri of mice and the correlation between the patterns of Ifitm1 gene expression and Wnt/β-catenin signalling discussed.

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24

Kutilin, D. S., I. S. Nikitin, and O. I. Kit. "Features of some transcription factors gene expression in the malignancy tissues of the corpus uteri." Advances in molecular oncology 6, no. 1 (April 28, 2019): 57–62. http://dx.doi.org/10.17650/2313-805x-2019-6-1-57-62.

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Dimitrova, Irina K., Jennifer K. Richer, Michael C. Rudolph, Nicole S. Spoelstra, Elaine M. Reno, Theresa M. Medina, and Andrew P. Bradford. "Gene expression profiling of multiple leiomyomata uteri and matched normal tissue from a single patient." Fertility and Sterility 91, no. 6 (June 2009): 2650–63. http://dx.doi.org/10.1016/j.fertnstert.2008.03.071.

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26

Richter, O. N. "Oxytocin receptor gene expression of estrogen-stimulated human myometrium in extracorporeally perfused non-pregnant uteri." Molecular Human Reproduction 10, no. 5 (March 25, 2004): 339–46. http://dx.doi.org/10.1093/molehr/gah039.

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27

Fuchs, A.-R., R. Ivell, P. A. Fields, S.-M. T. Chang, and M. J. Fields. "Oxytocin Receptors in Bovine Cervix: Distribution and Gene Expression during the Estrous Cycle1." Biology of Reproduction 54, no. 3 (March 1, 1996): 700–708. http://dx.doi.org/10.1095/biolreprod54.3.700.

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28

Bukowski, Radek, Gary D. V. Hankins, George R. Saade, Garland D. Anderson, and Steven Thornton. "Labor-Associated Gene Expression in the Human Uterine Fundus, Lower Segment, and Cervix." PLoS Medicine 3, no. 6 (June 13, 2006): e169. http://dx.doi.org/10.1371/journal.pmed.0030169.

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Benson, G. V., H. Lim, B. C. Paria, I. Satokata, S. K. Dey, and R. L. Maas. "Mechanisms of reduced fertility in Hoxa-10 mutant mice: uterine homeosis and loss of maternal Hoxa-10 expression." Development 122, no. 9 (September 1, 1996): 2687–96. http://dx.doi.org/10.1242/dev.122.9.2687.

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The establishment of a receptive uterine environment is critical for embryonic survival and implantation. One gene that is expressed in the uterus during the peri-implantation period in mice and is required for female fertility is the homeobox gene Hoxa-10. Here we characterize the peri-implantation defects in Hoxa-10 mutant females and investigate functions of Hoxa-10 in the uterine anlage during morphogenesis and in the adult uterus during pregnancy. Examination of pregnancy in Hoxa-10 mutant females has revealed failure of implantation as well as resorption of embryos in the early postimplantation period. Morphologic analysis of the mutant uterus has demonstrated homeotic transformation of the proximal 25% into oviduct. Histology and molecular markers confirm this anterior transformation. Furthermore, in situ hybridization shows that this region coincides with the anterior limit of embryonic Hoxa-10 expression in the urogenital ducts and a parallel transformation is observed in Hoxa-10 mutant males at the junction of the epididymis and ductus deferens. Female fertility could be compromised by either the homeotic transformation or the absence of Hoxa-10 function in the adult during pregnancy. To distinguish between these two potential mechanisms of infertility, wildtype blastocysts were transferred into mutant uteri distal to the transformed region on day 2.5 of pseudopregnancy. This procedure did not rescue the phenotype, suggesting that adult uterine expression of Hoxa-10 is required during pregnancy. Moreover, when implantation was experimentally delayed, homozygous uteri were able to support survival of blastocysts comparable to wild-type controls, indicating that the requirement for Hoxa-10 is intrinsic to implantation. While expression of LIF and HB-EGF appears unaffected in the mutant uteri, a decrease is observed in the intensity and number of blue dye reactions, an indicator of increased vascular permeability in response to implantation. In addition, mutant uteri exhibited decreased decidualization in response to artificial stimuli. These results show that Hoxa-10 is required during morphogenesis for proper patterning of the reproductive tract and in the adult uterus for peri-implantation events.

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Riethdorf, Sabine, Lutz Riethdorf, Karin Milde-Langosch, Tjoung-Won Park, and Thomas Löning. "Differences in HPV 16- and HPV 18 E6/E7 oncogene expression between in situ and invasive adenocarcinomas of the cervix uteri." Virchows Archiv 437, no. 5 (November 21, 2000): 491–500. http://dx.doi.org/10.1007/s004280000277.

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Mesa, Ana M., Jiude Mao, Manjunatha K. Nanjappa, Theresa I. Medrano, Sergei Tevosian, Fahong Yu, Jessica Kinkade, et al. "Mice lacking uterine enhancer of zeste homolog 2 have transcriptomic changes associated with uterine epithelial proliferation." Physiological Genomics 52, no. 2 (February 1, 2020): 81–95. http://dx.doi.org/10.1152/physiolgenomics.00098.2019.

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Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that suppresses gene expression. Previously, we developed a conditional null model where EZH2 is knocked out in uterus. Deletion of uterine EZH2 increased proliferation of luminal and glandular epithelial cells. Herein, we used RNA-Seq in wild-type (WT) and EZH2 conditional knockout ( Ezh2cKO) uteri to obtain mechanistic insights into the gene expression changes that underpin the pathogenesis observed in these mice. Ovariectomized adult Ezh2cKO mice were treated with vehicle (V) or 17β-estradiol (E2; 1 ng/g). Uteri were collected at postnatal day (PND) 75 for RNA-Seq or immunostaining for epithelial proliferation. Weighted gene coexpression network analysis was used to link uterine gene expression patterns and epithelial proliferation. In V-treated mice, 88 transcripts were differentially expressed (DEG) in Ezh2cKO mice, and Bmp5, Crabp2, Lgr5, and Sprr2f were upregulated. E2 treatment resulted in 40 DEG with Krt5, Krt15, Olig3, Crabp1, and Serpinb7 upregulated in Ezh2cKO compared with control mice. Transcript analysis relative to proliferation rates revealed two module eigengenes correlated with epithelial proliferation in WT V vs. Ezh2cKO V and WT E2 vs. Ezh2cKO E2 mice, with a positive relationship in the former and inverse in the latter. Notably, the ESR1, Wnt, and Hippo signaling pathways were among those functionally enriched in Ezh2cKO females. Current results reveal unique gene expression patterns in Ezh2cKO uterus and provide insight into how loss of this critical epigenetic regulator assumingly contributes to uterine abnormalities.

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Ikeda, Mario, M. Taga, H. Sakakibara, H. Minaguchi, E. Ginsburg, and B. K. Vonderhaar. "Gene expression of gonadotropin-releasing hormone in early pregnant rat and steroid hormone exposed mouse uteri." Journal of Endocrinological Investigation 19, no. 11 (December 1996): 708–13. http://dx.doi.org/10.1007/bf03347872.

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33

Fuchs, Anna-Riitta, Richard Ivell, Marga Balvers, Shou-Mei Chang, and Michael J. Fields. "Oxytocin receptors in bovine cervix during pregnancy and parturition: Gene expression and cellular localization." American Journal of Obstetrics and Gynecology 175, no. 6 (December 1996): 1654–60. http://dx.doi.org/10.1016/s0002-9378(96)70121-7.

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34

Contag, Stephen A., Bobbie S. Gostout, Amy C. Clayton, Melanie H. Dixon, Renee M. McGovern, and Eric S. Calhoun. "Comparison of gene expression in squamous cell carcinoma and adenocarcinoma of the uterine cervix." Gynecologic Oncology 95, no. 3 (December 2004): 610–17. http://dx.doi.org/10.1016/j.ygyno.2004.08.021.

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35

McClure, C. Patrick, Patrick J. Tighe, R. Adrian Robins, Deepa Bansal, Christine A. Bowman, Margaret Kingston, and Jonathan K. Ball. "HIV coreceptor and chemokine ligand gene expression in the male urethra and female cervix." AIDS 19, no. 12 (August 2005): 1257–65. http://dx.doi.org/10.1097/01.aids.0000180096.50393.96.

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36

Chen, Jie, Ziyi Fu, Chenbo Ji, Pingqing Gu, Pengfei Xu, Ningzhu Yu, Yansheng Kan, Xiaowei Wu, Rong Shen, and Yan Shen. "Systematic gene microarray analysis of the lncRNA expression profiles in human uterine cervix carcinoma." Biomedicine & Pharmacotherapy 72 (May 2015): 83–90. http://dx.doi.org/10.1016/j.biopha.2015.04.010.

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37

Edelmann, J., K. Richter, C. HÄNEL, S. Hering, and L. C. Horn. "X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma." International Journal of Gynecologic Cancer 16, no. 3 (2006): 1248–53. http://dx.doi.org/10.1136/ijgc-00009577-200605000-00045.

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The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4–40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21–40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.

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Rider, Virginia, Kazuto Isuzugawa, Meryl Twarog, Stacy Jones, Brent Cameron, Kazuhiko Imakawa, and Jianwen Fang. "Progesterone initiates Wnt-β-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells." Journal of Endocrinology 191, no. 3 (December 2006): 537–48. http://dx.doi.org/10.1677/joe.1.07030.

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Progesterone pretreatment of ovariectomized rat uteri increases the number of synchronously proliferating stromal cells in response to estradiol 17-β. To identify the signals involved in stimulating synchronous proliferation, sexually mature ovariectomized rats were injected with progesterone (2 mg) for 3 consecutive days. Estradiol 17-β (0.2 μg) was administered to initiate cell cycle entry. Uterine samples were removed at various times after hormone administration and changes in wingless (Wnt) pathway effectors and gene targets were identified by microarray. Progesterone pretreatment decreased glycogen synthase kinase-3β (GSK-3β) and increased expression of T-cell factor/lymphoid enhancer factor (TCF/LEF). GSK-3β protein decreased markedly in the uterine stroma of progesterone-pretreated uteri with the concomitant appearance of β-catenin in these stromal cells. Translocation of β-catenin from the cytosol to the nuclei in progesterone-pretreated stromal cells was stimulated in response to estradiol. β-Catenin binding to TCF/LEF increased (P<0.05) in progesterone-pretreated uteri in response to estradiol. Progesterone stimulated the expression of the Wnt target gene urokinase plasminogen activator receptor (uPA-R) in the periluminal uterine stromal cells. The expression of uPA-R increased in progesterone-pretreated stromal cells in response to estradiol administration. Together, the results indicate that progesterone initiates Wnt signaling in the uterine stroma by down-regulating GSK-3β. However, nuclear translocation of β-catenin and sufficient complex formation with TCF/LEF to activate stromal cell cycle entry requires estradiol. Stimulation of a uterine stromal cell line to proliferate and differentiate resulted in β-catenin accumulation, suggesting that endocrine-dependent Wnt signaling controls proliferation and differentiation (decidualization).

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39

Davis, Angela M., Jiude Mao, Bushra Naz, Jessica A. Kohl, and Cheryl S. Rosenfeld. "Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus." Journal of Molecular Endocrinology 41, no. 4 (July 16, 2008): 205–17. http://dx.doi.org/10.1677/jme-08-0029.

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Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17β-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.

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40

Nanjappa, Manjunatha K., Ana M. Mesa, Theresa I. Medrano, Wendy N. Jefferson, Francesco J. DeMayo, Carmen J. Williams, John P. Lydon, Ellis R. Levin, and Paul S. Cooke. "The histone methyltransferase EZH2 is required for normal uterine development and function in mice†." Biology of Reproduction 101, no. 2 (June 14, 2019): 306–17. http://dx.doi.org/10.1093/biolre/ioz097.

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Abstract Enhancer of zeste homolog 2 (EZH2) is a rate-limiting catalytic subunit of a histone methyltransferase, polycomb repressive complex, which silences gene activity through the repressive histone mark H3K27me3. EZH2 is critical for epigenetic effects of early estrogen treatment, and may be involved in uterine development and pathologies. We investigated EZH2 expression, regulation, and its role in uterine development/function. Uterine epithelial EZH2 expression was associated with proliferation and was high neonatally then declined by weaning. Pre-weaning uterine EZH2 expression was comparable in wild-type and estrogen receptor 1 knockout mice, showing neonatal EZH2 expression is ESR1 independent. Epithelial EZH2 was upregulated by 17β-estradiol (E2) and inhibited by progesterone in adult uteri from ovariectomized mice. To investigate the uterine role of EZH2, we developed a EZH2 conditional knockout (Ezh2cKO) mouse using a cre recombinase driven by the progesterone receptor (Pgr) promoter that produced Ezh2cKO mice lacking EZH2 in Pgr-expressing tissues (e.g. uterus, mammary glands). In Ezh2cKO uteri, EZH2 was deleted neonatally. These uteri had reduced H3K27me3, were larger than WT, and showed adult cystic endometrial hyperplasia. Ovary-independent uterine epithelial proliferation and increased numbers of highly proliferative uterine glands were seen in adult Ezh2cKO mice. Female Ezh2cKO mice were initially subfertile, and then became infertile by 9 months. Mammary gland development in Ezh2cKO mice was inhibited. In summary, uterine EZH2 expression is developmentally and hormonally regulated, and its loss causes aberrant uterine epithelial proliferation, uterine hypertrophy, and cystic endometrial hyperplasia, indicating a critical role in uterine development and function.

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Jeong, Jae-Wook, Kevin Y. Lee, Sang Jun Han, Bruce J. Aronow, John P. Lydon, Bert W. O’Malley, and Francesco J. DeMayo. "The p160 Steroid Receptor Coactivator 2, SRC-2, Regulates Murine Endometrial Function and Regulates Progesterone-Independent and -Dependent Gene Expression." Endocrinology 148, no. 9 (September 1, 2007): 4238–50. http://dx.doi.org/10.1210/en.2007-0122.

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The role of the p160 steroid receptor coactivator 2 (SRC-2) in the regulation of uterine function and progesterone (P4) signaling was investigated by determining the expression pattern of SRC-2 in the murine uterus during pregnancy and the impact of SRC-2 ablation on uterine function and global uterine gene expression in response to progesterone. SRC-2 is expressed in the endometrial luminal and glandular epithelium from pregnancy d 0.5. SRC-2 is then expressed in the endometrial stroma on pregnancy d 2.5–3.5. Once the embryo is implanted, SRC-2 is expressed in the endometrial stromal cells in the secondary decidual zone. This compartmental expression of SRC-2 can be mimicked by treatment of ovariectomized mice with estrogen and P4. Ablation of SRC-2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Microarray analysis of RNA from uteri of wild-type and SRC-2−/− mice treated with vehicle or P4 showed that SRC-2 was involved in the ability of progesterone to repress specific genes. This microarray analysis also revealed that the uteri of SRC-2−/− mice showed alterations in genes involved in estrogen receptor, Wnt, and bone morphogenetic protein signaling. This analysis indicates that SRC-2 regulates uterine function by modulating the regulation of developmentally important signaling molecules and the ability of P4 to repress specific genes.

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42

Brumm, C., A. Rivière, C. Wilckens, and T. Löning. "Immunohistochemical investigation and Northern blot analysis of c-erbB-2 expression in normal, premalignant and malignant tissues of the corpus and cervix uteri." Virchows Archiv A Pathological Anatomy and Histopathology 417, no. 6 (November 1990): 477–84. http://dx.doi.org/10.1007/bf01625727.

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43

Grinstein, Edgar, Peter Wernet, Peter J. F. Snijders, Frank Rösl, Inge Weinert, Wentao Jia, Regine Kraft, et al. "Nucleolin as Activator of Human Papillomavirus Type 18 Oncogene Transcription in Cervical Cancer." Journal of Experimental Medicine 196, no. 8 (October 21, 2002): 1067–78. http://dx.doi.org/10.1084/jem.20011053.

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High risk human papillomaviruses (HPVs) are central to the development of cervical cancer and the deregulated expression of high risk HPV oncogenes is a critical event in this process. Here, we find that the cell protein nucleolin binds in a sequence-specific manner to the HPV18 enhancer. The DNA binding activity of nucleolin is primarily S phase specific, much like the transcription of the E6 and E7 oncoproteins of HPV18 in cervical cancer cells. Antisense inactivation of nucleolin blocks E6 and E7 oncogene transcription and selectively decreases HPV18+ cervical cancer cell growth. Furthermore, nucleolin controls the chromatin structure of the HPV18 enhancer. In contrast, HPV16 oncogene transcription and proliferation rates of HPV16+ SiHa cervical cancer cells are independent of nucleolin activity. Moreover, nucleolin expression is altered in HPV18+ precancerous and cancerous tissue from the cervix uteri. Whereas nucleolin was homogeneously distributed in the nuclei of normal epithelial cells, it showed a speckled nuclear phenotype in HPV18+ carcinomas. Thus, the host cell protein nucleolin is directly linked to HPV18-induced cervical carcinogenesis.

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44

Fertuck, K. C., J. E. Eckel, C. Gennings, and T. R. Zacharewski. "Identification of temporal patterns of gene expression in the uteri of immature, ovariectomized mice following exposure to ethynylestradiol." Physiological Genomics 15, no. 2 (October 17, 2003): 127–41. http://dx.doi.org/10.1152/physiolgenomics.00058.2003.

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Estrogen induction of uterine wet weight provides an excellent model to investigate relationships between changes in global gene expression and well-characterized physiological responses. In this study, time course microarray GeneChip data were analyzed using a novel approach to identify temporal changes in uterine gene expression following treatment of immature ovariectomized C57BL/6 mice with 0.1 mg/kg 17α-ethynylestradiol. Functional gene annotation information from public databases facilitated the association of changes in gene expression with physiological outcomes, which allowed detailed mechanistic inferences to be drawn regarding cell cycle control and proliferation, transcription and translation, structural tissue remodeling, and immunologic responses. These systematic approaches confirm previously established responses, identify novel estrogen-regulated transcriptional effects, and disclose the coordinated activation of multiple modes of action that support the uterotrophic response elicited by estrogen. In particular, it was possible to elucidate the physiological significance of the dramatic induction of arginase, a classic estrogenic response, by elucidating its mechanistic relevance and delineating the role of arginine and ornithine utilization in the estrogen-stimulated induction of uterine wet weight.

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45

Riethdorf, Lutz, Sabine Riethdorf, Sonja Petersen, Michael Bauer, Hermann Herbst, Fritz J�nicke, and Thomas L�ning. "Urokinase gene expression indicates early invasive growth in squamous cell lesions of the uterine cervix." Journal of Pathology 189, no. 2 (October 1999): 245–50. http://dx.doi.org/10.1002/(sici)1096-9896(199910)189:2<245::aid-path427>3.0.co;2-z.

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46

杨, 梅. "Research on Expression of Telomerase hTERC Gene and Infection of High Risk HPV in Cervix." Asian Case Reports in Oncology 07, no. 04 (2018): 51–55. http://dx.doi.org/10.12677/acrpo.2018.74008.

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47

Dobyns, Abigail E., Ravi Goyal, Lauren Grisham Carpenter, Tom C. Freeman, Lawrence D. Longo, and Steven M. Yellon. "Macrophage Gene Expression Associated with Remodeling of the Prepartum Rat Cervix: Microarray and Pathway Analyses." PLOS ONE 10, no. 3 (March 26, 2015): e0119782. http://dx.doi.org/10.1371/journal.pone.0119782.

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48

Hassan, Sonia, Roberto Romero, Adi L. Tarca, Sorin Draghici, Nahla Khalek, Natalia Camacho, Pooja Mittal, et al. "Gene expression signature pathways in the human uterine cervix before and after spontaneous term parturition." American Journal of Obstetrics and Gynecology 195, no. 6 (December 2006): S30. http://dx.doi.org/10.1016/j.ajog.2006.10.080.

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49

Waggoner, Steven E., Steven M. Anderson, Michael C. Luce, Hiroyuki Takahashi, and Jeff Boyd. "p53 Protein Expression and Gene Analysis in Clear Cell Adenocarcinoma of the Vagina and Cervix." Gynecologic Oncology 60, no. 3 (March 1996): 339–44. http://dx.doi.org/10.1006/gyno.1996.0052.

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50

Guzeloglu-Kayisli, Ozlem, Nihan Semerci, Xiaofang Guo, Kellie Larsen, Asli Ozmen, Sefa Arlier, Duygu Mutluay, et al. "Decidual cell FKBP51–progesterone receptor binding mediates maternal stress–induced preterm birth." Proceedings of the National Academy of Sciences 118, no. 11 (March 8, 2021): e2010282118. http://dx.doi.org/10.1073/pnas.2010282118.

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Depression and posttraumatic stress disorder increase the risk of idiopathic preterm birth (iPTB); however, the exact molecular mechanism is unknown. Depression and stress-related disorders are linked to increased FK506-binding protein 51 (FKBP51) expression levels in the brain and/or FKBP5 gene polymorphisms. Fkbp5-deficient (Fkbp5−/−) mice resist stress-induced depressive and anxiety-like behaviors. FKBP51 binding to progesterone (P4) receptors (PRs) inhibits PR function. Moreover, reduced PR activity and/or expression stimulates human labor. We report enhanced in situ FKBP51 expression and increased nuclear FKBP51-PR binding in decidual cells of women with iPTB versus gestational age-matched controls. In Fkbp5+/+ mice, maternal restraint stress did not accelerate systemic P4 withdrawal but increased Fkbp5, decreased PR, and elevated AKR1C18 expression in uteri at E17.25 followed by reduced P4 levels and increased oxytocin receptor (Oxtr) expression at 18.25 in uteri resulting in PTB. These changes correlate with inhibition of uterine PR function by maternal stress–induced FKBP51. In contrast, Fkbp5−/− mice exhibit prolonged gestation and are completely resistant to maternal stress–induced PTB and labor-inducing uterine changes detected in stressed Fkbp5+/+ mice. Collectively, these results uncover a functional P4 withdrawal mechanism mediated by maternal stress–induced enhanced uterine FKBP51 expression and FKPB51-PR binding, resulting in iPTB.

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