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1

Dickson, S. R., and M. J. Warburton. "Enhanced synthesis of gelatinase and stromelysin by myoepithelial cells during involution of the rat mammary gland." Journal of Histochemistry & Cytochemistry 40, no. 5 (1992): 697–703. http://dx.doi.org/10.1177/40.5.1315355.

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During the involution of the mammary gland there is destruction of the basement membrane as the secretory alveolar structures degenerate. Immunofluorescence staining of sections of rat mammary gland with antibodies to 72 KD gelatinase (MMP-2) and stromelysin (MMP-3) revealed increased production of these two proteinases during involution. This increased expression was mostly restricted to myoepithelial cells. Increased expression during involution was also demonstrated by immunoblotting techniques. Gelatin zymography indicated that the predominant metalloproteinase present in involuting rat ma
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Lund, L. R., S. F. Bjorn, M. D. Sternlicht, et al. "Lactational competence and involution of the mouse mammary gland require plasminogen." Development 127, no. 20 (2000): 4481–92. http://dx.doi.org/10.1242/dev.127.20.4481.

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Urokinase-type plasminogen activator expression is induced in the mouse mammary gland during development and post-lactational involution. We now show that primiparous plasminogen-deficient (Plg(−/−)) mice have seriously compromised mammary gland development and involution. All mammary glands were underdeveloped and one-quarter of the mice failed to lactate. Although the glands from lactating Plg(−/−) mice were initially smaller, they failed to involute after weaning, and in most cases they failed to support a second litter. Alveolar regression was markedly reduced and a fibrotic stroma accumul
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Talhouk, R. S., M. J. Bissell, and Z. Werb. "Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution." Journal of Cell Biology 118, no. 5 (1992): 1271–82. http://dx.doi.org/10.1083/jcb.118.5.1271.

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Extracellular matrix (ECM) plays an important role in the maintenance of mammary epithelial differentiation in culture. We asked whether changes in mouse mammary specific function in vivo correlate with changes in the ECM. We showed, using expression of beta-casein as a marker, that the temporal expression of ECM-degrading proteinases and their inhibitors during lactation and involution are inversely related to functional differentiation. After a lactation period of 9 d, mammary epithelial cells maintained beta-casein expression up to 5 d of involution. Two metalloproteinases, 72-kD gelatinase
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Tian, Lei, Shancheng Guo, Zhiye Zhao, et al. "miR-30a-3p Regulates Autophagy in the Involution of Mice Mammary Glands." International Journal of Molecular Sciences 24, no. 18 (2023): 14352. http://dx.doi.org/10.3390/ijms241814352.

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The mammary gland undergoes intensive remodeling during the lactation cycle, and the involution process of mammary gland contains extensive epithelial cells involved in the process of autophagy. Our studies of mice mammary glands suggest that miR-30a-3p expression was low during involution compared with its high expression in the mammary glands of lactating mice. Then, we revealed that miR-30a-3p negatively regulated autophagy by autophagy related 12 (Atg12) in mouse mammary gland epithelial cells (MMECs). Restoring ATG12, knocking down autophagy related 5 (Atg5), starvation, and Rapamycin wer
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Batan, Sonia, Jabunnesa Khanom, Sabarish Ramachandran, et al. "Abstract P3-04-04: The Butyrate Transporter SLC5A8 Selectively Inhibits Breast Tumor Metastasis." Clinical Cancer Research 31, no. 12_Supplement (2025): P3–04–04—P3–04–04. https://doi.org/10.1158/1557-3265.sabcs24-p3-04-04.

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Abstract Introduction: The mammary gland is a dynamic organ that undergoes significant developmental changes during pregnancy, lactation, and involution. The process of involution is a highly orchestrated series of molecular and physical events that can be divided into two distinct phases. (Lund et al., 1996). Accumulation of milk in the alveolar lumen (milk stasis) is required to initiate the first phase during which the secretory cells begin to enter apoptosis. Here we provide genetic and molecular biological evidence to shows that the short-chain fatty acid Butyrate (BTR), a significant com
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Schwertfeger, Kathryn L., Monica M. Richert, and Steven M. Anderson. "Mammary Gland Involution Is Delayed by Activated Akt in Transgenic Mice." Molecular Endocrinology 15, no. 6 (2001): 867–81. http://dx.doi.org/10.1210/mend.15.6.0663.

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Abstract Activation of the antiapoptotic protein kinase Akt is induced by a number of growth factors that regulate mammary gland development. Akt is expressed during mammary gland development, and expression decreases at the onset of involution. To address Akt actions in mammary gland development, transgenic mice were generated expressing constitutively active Akt in the mammary gland under the control of the mouse mammary tumor virus (MMTV) promoter. Analysis of mammary glands from these mice reveals a delay in both involution and the onset of apoptosis. Expression of tissue inhibitor of meta
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Bernhardt, Sarah M., and Pepper Schedin. "Abstract B011: The anti-cancer effects of vitamin D are blocked postpartum, due to suppression of vitamin D metabolism in the involuting liver." Cancer Prevention Research 15, no. 12_Supplement_1 (2022): B011. http://dx.doi.org/10.1158/1940-6215.dcis22-b011.

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Abstract Postpartum mammary gland involution is a physiologic window of increased breast cancer risk. It has been proposed that the poor prognosis associated with postpartum breast cancer is due to the involuting mammary microenvironment promoting progression of indolent lesions to invasive disease. As such, the involuting gland has been implicated as a target for preventive strategies. Vitamin D has anti-cancer properties, and there are data demonstrating that vitamin D supplementation protects against breast cancer progression in mouse models. Moreover, vitamin D deficiency is prevalent in p
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Jena, Manoj Kumar, and Ashok Kumar Mohanty. "NEW INSIGHTS OF MAMMARY GLAND DURING DIFFERENT STAGES OF DEVELOPMENT." Asian Journal of Pharmaceutical and Clinical Research 10, no. 11 (2017): 35. http://dx.doi.org/10.22159/ajpcr.2017.v10i11.20801.

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Mammary gland is a unique organ with its function of milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells proliferate, differentiate, undergo apoptosis, and tissue remodeling following a cyclic pathway in lactation – involution – lactation cycle, thus fine tuning the molecular events through hormones, and regulatory molecules. Several studies are performed on the mammary gland development, lactogenesis, and involution process in molecular details. The developmental stages of mammary gland are embryonic, pre-pubertal, pubertal, pr
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Atabai, Kamran, Rafael Fernandez, Xiaozhu Huang, et al. "Mfge8 Is Critical for Mammary Gland Remodeling during Involution." Molecular Biology of the Cell 16, no. 12 (2005): 5528–37. http://dx.doi.org/10.1091/mbc.e05-02-0128.

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Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with the release of intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to facilitate the clearance of apoptotic lymphocytes by splenic macrophages. We report that mice with disruption of Mfge8 had normal mammary gland development until involution. However, abnormal mammary gland remodeling was observed postlactation in Mfg
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Rivera, Olivia C., Stephen R. Hennigar, and Shannon L. Kelleher. "ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 315, no. 2 (2018): R323—R335. http://dx.doi.org/10.1152/ajpregu.00444.2017.

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Mammary gland involution, a tightly regulated process of tissue remodeling by which a lactating mammary gland reverts to the prepregnant state, is characterized by the most profound example of regulated epithelial cell death in normal tissue. Defects in the execution of involution are associated with lactation failure and breast cancer. Initiation of mammary gland involution requires upregulation of lysosome biogenesis and acidification to activate lysosome-mediated cell death; however, specific mediators of this initial phase of involution are not well described. Zinc transporter 2 [ZnT2 ( SL
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Feng, Z., A. Marti, B. Jehn, H. J. Altermatt, G. Chicaiza, and R. Jaggi. "Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland." Journal of Cell Biology 131, no. 4 (1995): 1095–103. http://dx.doi.org/10.1083/jcb.131.4.1095.

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Milk production during lactation is a consequence of the suckling stimulus and the presence of glucocorticoids, prolactin, and insulin. After weaning the glucocorticoid hormone level drops, secretory mammary epithelial cells die by programmed cell death and the gland is prepared for a new pregnancy. We studied the role of steroid hormones and prolactin on the mammary gland structure, milk protein synthesis, and on programmed cell death. Slow-release plastic pellets containing individual hormones were implanted into a single mammary gland at lactation. At the same time the pups were removed and
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Alexander, Caroline M., Sushma Selvarajan, John Mudgett, and Zena Werb. "Stromelysin-1 Regulates Adipogenesis during Mammary Gland Involution." Journal of Cell Biology 152, no. 4 (2001): 693–703. http://dx.doi.org/10.1083/jcb.152.4.693.

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The matrix metalloproteinase MMP-3/stromelysin-1 (Str1) is highly expressed during mammary gland involution induced by weaning. During involution, programmed cell death of the secretory epithelium takes place concomitant with the repopulation of the mammary fat pad with adipocytes. In this study, we have used a genetic approach to determine the role of Str1 during mammary involution. Although Str1 has been shown to induce unscheduled apoptosis when expressed ectopically during late pregnancy (Alexander, C.M., E.W. Howard, M.J. Bissell, and Z. Werb. 1996. J. Cell Biol. 135:1669–1677), we found
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Lu, Jie, Guohao Huang, Xuan Chang, et al. "Effects of Serotonin on Cell Viability, Permeability of Bovine Mammary Gland Epithelial Cells and Their Transcriptome Analysis." International Journal of Molecular Sciences 24, no. 14 (2023): 11388. http://dx.doi.org/10.3390/ijms241411388.

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Serotonin (5-HT) has been reported to play an important role in mammary gland involution that is defined as the process through which the gland returns to a nonlactating state. However, the overall picture of the regulatory mechanisms of 5-HT and the effects of serotonylation on mammary gland involution still need to be further investigated. The current study aimed to investigate the effects of 5-HT on global gene expression profiles of bovine mammary epithelial cells (MAC-T) and to preliminarily examine whether the serotonylation involved in the mammary gland involution by using Monodansylcad
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Adriani, Adriani. "Hubungan Involusi Sel-sel Sekretoris Kelenjar Ambing dengan Produksi Susu Domba Priangan dengan Dua Level Pakan." Jurnal Ilmiah Ilmu-Ilmu Peternakan 12, no. 3 (2009): 118–24. http://dx.doi.org/10.22437/jiiip.v0i0.173.

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Forty-two lactating Priangan ewes receiving two levels of ration were used to study the relationship between rate of mammary gland involution and milk yield. The experimental ewes were divided into two groups. One group received basal ration (I = 12% CP, 65% TDN) and the other received improved ration (II = 15% CP, 75% TDN) during lactation. Twelve ewes were sacrificed on the parturition to determine mammary gland growth at the beginning of lactation. The other twenty-seven were maintained for 3 months of lactating to determine milk yield and mammary gland indices (dry-fat free tissue and coll
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15

Ning, Yun, Bao Hoang, Alwin G. P. Schuller, et al. "Delayed Mammary Gland Involution in Mice with Mutation of the Insulin-Like Growth Factor Binding Protein 5 Gene." Endocrinology 148, no. 5 (2007): 2138–47. http://dx.doi.org/10.1210/en.2006-0041.

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IGFs (IGF-I and IGF-II) are essential for development, and their bioactivities are tightly regulated by six related IGF-binding proteins (IGFBPs). IGFBP-5 is the most highly conserved binding protein and is expressed in several key developmental lineages as well as in multiple adult tissues including the mammary gland. To explore IGFBP-5 actions in vivo, we produced IGFBP-5 knockout (KO) mice. Whole-body growth, selected organ weights, and body composition were essentially normal in IGFBP-5 KO mice, presumably because of substantial compensation by remaining IGFBP family members. The IGFBP-5 K
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Xuan, Rong, Jianmin Wang, Xiaodong Zhao, et al. "Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution." International Journal of Molecular Sciences 23, no. 22 (2022): 14424. http://dx.doi.org/10.3390/ijms232214424.

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To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesi
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Hurley, W. L. "Mammary Gland Function During Involution." Journal of Dairy Science 72, no. 6 (1989): 1637–46. http://dx.doi.org/10.3168/jds.s0022-0302(89)79276-6.

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CVEK, KATARINA, KRISTINA DAHLBORN, and YVONNE RIDDERSTRÅLE. "Localization of carbonic anhydrase in the goat mammary gland during involution and lactogenesis." Journal of Dairy Research 65, no. 1 (1998): 43–54. http://dx.doi.org/10.1017/s0022029997002537.

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The aim of this study was to determine whether carbonic anhydrase (CA) activity in goat mammary capillaries is regulated mainly by local or systemic mechanisms. One gland was dried before the contralateral gland, and after parturition only one gland was milked. Biopsies were taken from the mammary glands of three goats at 14 d intervals during involution and the start of the following lactation. A histochemical method was used to visualize sites of CA activity. To follow the involution process, milk (liquid) samples were taken from both teats each week and analysed for pH and composition. The
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Yi, Yijun, Anne Shepard, Frances Kittrell, Biserka Mulac-Jericevic, Daniel Medina, and Thenaa K. Said. "p19ARFDetermines the Balance between Normal Cell Proliferation Rate and Apoptosis during Mammary Gland Development." Molecular Biology of the Cell 15, no. 5 (2004): 2302–11. http://dx.doi.org/10.1091/mbc.e03-11-0785.

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This study demonstrated, for the first time, the following events related to p19ARFinvolvement in mammary gland development: 1) Progesterone appears to regulate p19ARFin normal mammary gland during pregnancy. 2) p19ARFexpression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19ARFprotein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19ARFin mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulat
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Li, Meng, Qingzhang Li, and Xuejun Gao. "Expression and function of leptin and its receptor in dairy goat mammary gland." Journal of Dairy Research 77, no. 2 (2010): 213–19. http://dx.doi.org/10.1017/s0022029910000063.

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Leptin is an autocrine and paracrine factor which affects the development and function of mammary gland. The purpose of this study was to investigate the presence and regulatory effect of leptin in Chinese Guan Zhong dairy goat mammary gland from the virgin state to involution. The protein expression and localization of leptin and its long form receptor (OB-Rb) were detected by western blot and a confocal laser scanning microscope. Explants were cultured to detect the impacts of leptin on mammary gland, western blot was used to research leptin signal transduction pathway in pregnancy, lactatio
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Oliver, S. P., and T. Bushe. "Growth inhibition of Escherichia coli and Klebsiella pneumoniae during involution of the bovine mammary gland: Relation to secretion composition." American Journal of Veterinary Research 48, no. 12 (1987): 1669–73. https://doi.org/10.2460/ajvr.1987.48.12.1669.

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SUMMARY Mammary secretions from 12 Holstein dairy cows were collected to evaluate growth inhibition of Escherichia coli and Klebsiella pneumoniae during involution and during physiologic transitions of the mammary gland. Mammary secretions obtained during late lactation poorly inhibited growth of E coli and K pneumoniae. However, as involution progressed, mammary secretions increasingly inhibited growth of both coliform mastitis pathogens. Greatest inhibition of E coli and K pneumoniae growth was observed when mammary glands were fully involuted. Growth inhibition remained high until 7 days be
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Munarini, Nadia, Richard Jäger, Susanne Abderhalden, et al. "Altered mammary epithelial development, pattern formation and involution in transgenic mice expressing the EphB4 receptor tyrosine kinase." Journal of Cell Science 115, no. 1 (2002): 25–37. http://dx.doi.org/10.1242/jcs.115.1.25.

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We have previously documented the cell-type-specific and hormone-dependent expression of the EphB4 receptor in the mouse mammary gland. To investigate its role in the biology of the mammary gland, we have established transgenic mice bearing the EphB4 receptor under the control of the MMTV-LTR promoter, which represents the first transgenic mouse model to investigate the effect(s) of unscheduled expression of EphB4 in adult organisms. Transgene expression in the mammary epithelium was induced at puberty, increased during pregnancy, culminated at early lactation and persisted until day three of
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TATARCZUCH, L., C. PHILIP, and C. S. LEE. "Involution of the sheep mammary gland." Journal of Anatomy 190, no. 3 (1997): 405–16. http://dx.doi.org/10.1046/j.1469-7580.1997.19030405.x.

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SOHN, B. Hwa, Hyung-Bae MOON, Tae-Yoon KIM та ін. "Interleukin-10 up-regulates tumour-necrosis-factor-α-related apoptosis-inducing ligand (TRAIL) gene expression in mammary epithelial cells at the involution stage". Biochemical Journal 360, № 1 (2001): 31–38. http://dx.doi.org/10.1042/bj3600031.

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Although interleukin-10 (IL-10) is known to contribute to inflammation and pathogenesis in mammalian organs, little is known about its precise role in the mammary gland. We found that IL-10 levels fluctuated during the mouse mammary cycle, showing little expression at the lactation stage and the highest expression at the involution stage. To reveal the effects of IL-10 on involution, expression profiles of apoptosis-related genes were examined in mice transgenic for IL-10 as well as in IL-10−/− mice. Mild inflammatory lesions by lymphocytes were observed in the mammary glands from four of seve
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SABATAKOS, Georgios, Gareth E. DAVIES, Maria GROSSE, Anthony CRYER, and Dipak P. RAMJI. "Expression of the genes encoding CCAAT-enhancer binding protein isoforms in the mouse mammary gland during lactation and involution." Biochemical Journal 334, no. 1 (1998): 205–10. http://dx.doi.org/10.1042/bj3340205.

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Transcription factors belonging to the CCAAT-enhancer binding protein (C/EBP) family have been implicated in the activation of gene expression in the mammary gland during lactation. We have therefore investigated the detailed expression profile of the C/EBP family during lactation and involution of the mouse mammary gland. The expression of C/EBPβ and C/EBPδ mRNA was low during lactation, increased dramatically at the beginning of involution and remained constant thereafter. In contrast, C/EBPα mRNA expression was relatively high during the early stages of lactation, declined to low levels dur
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Parés, Sílvia, Olivia Cano-Garrido, Alex Bach, et al. "The Potential of Metalloproteinase-9 Administration to Accelerate Mammary Involution and Boost the Immune System at Dry-Off." Animals 11, no. 12 (2021): 3415. http://dx.doi.org/10.3390/ani11123415.

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The dry period is decisive for the milking performance of dairy cows. The promptness of mammary gland involution at dry-off affects not only the productivity in the next lactation, but also the risk of new intra-mammary infections since it is closely related with the activity of the immune system. Matrix metalloproteinase-9 (MMP-9) is an enzyme present in the mammary gland and has an active role during involution by disrupting the extracellular matrix, mediating cell survival and the recruitment of immune cells. The objective of this study was to determine the potential of exogenous administra
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Lund, L. R., J. Romer, N. Thomasset, et al. "Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways." Development 122, no. 1 (1996): 181–93. http://dx.doi.org/10.1242/dev.122.1.181.

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Postlactational involution of the mammary gland is characterized by two distinct physiological events: apoptosis of the secretory, epithelial cells undergoing programmed cell death, and proteolytic degradation of the mammary gland basement membrane. We examined the spatial and temporal patterns of apoptotic cells in relation to those of proteinases during involution of the BALB/c mouse mammary gland. Apoptosis was almost absent during lactation but became evident at day 2 of involution, when beta-casein gene expression was still high. Apoptotic cells were then seen at least up to day 8 of invo
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Clemenceau, Alisson, Caroline Diorio, and Francine Durocher. "Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment." Cells 9, no. 1 (2020): 208. http://dx.doi.org/10.3390/cells9010208.

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In mice, the lack of secreted frizzled-related protein 1 (SFRP1) is responsible for mammogenesis and hyperplasia, while, in bovines, its overexpression is associated with post-lactational mammary gland involution. Interestingly, there are no reports dealing with the role of SFRP1 in female involution. However, SFRP1 dysregulation is largely associated with human tumorigenesis in the literature. Indeed, the lack of SFRP1 is associated with both tumor development and patient prognosis. Considering the increased risk of breast tumor development associated with incomplete mammary gland involution,
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Hadsell, Darryl L., Tatiana Alexeenko, Yann Klemintidis, Daniel Torres, and Adrian V. Lee. "Inability of Overexpressed des(1–3)Human Insulin-Like Growth Factor I (IGF-I) to Inhibit Forced Mammary Gland Involution Is Associated with Decreased Expression of IGF Signaling Molecules*." Endocrinology 142, no. 4 (2001): 1479–88. http://dx.doi.org/10.1210/endo.142.4.8087.

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Abstract Overexpression of des(1–3) human insulin-like growth factor I (IGF-I) in the mammary glands of transgenic mice (WAP-DES) inhibits apoptosis during natural, but not forced, mammary involution. We hypothesized that this differential response would correlate with the expression of IGF signal transducers. Forced and natural involution were analyzed in nontransgenic and WAP-DES mice beginning on day 16 postpartum. During natural involution, mammary gland wet weight was higher and apoptosis was lower in WAP-DES than in nontransgenic mice. The WAP-DES transgene had no effect on these paramet
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Muraoka, Rebecca S., Anne E. G. Lenferink, Jean Simpson, et al. "Cyclin-Dependent Kinase Inhibitor P27Kip1 Is Required for Mouse Mammary Gland Morphogenesis and Function." Journal of Cell Biology 153, no. 5 (2001): 917–32. http://dx.doi.org/10.1083/jcb.153.5.917.

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We have studied the role of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 in postnatal mammary gland morphogenesis. Based on its ability to negatively regulate cyclin/Cdk function, loss of p27 may result in unrestrained cellular proliferation. However, recent evidence about the stabilizing effect of p27 on cyclin D1–Cdk4 complexes suggests that p27 deficiency might recapitulate the hypoplastic mammary phenotype of cyclin D1–deficient animals. These hypotheses were investigated in postnatal p27-deficient (p27−/−), hemizygous (p27+/−), or wild-type (p27+/+) mammary glands. Mammary glands f
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Kennedy, S., and H. J. Ball. "Pathology of Experimental Ureaplasma Mastitis in Ewes." Veterinary Pathology 24, no. 4 (1987): 302–7. http://dx.doi.org/10.1177/030098588702400403.

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One mammary gland of each of nine primum partum suckling ewes was inoculated with ureaplasma 8 weeks post-partum. Infected glands were swollen, hot, and painful from 16 hours post-infection. Subsequently there was agalactia and reduction in gland size. Histopathologic and ultrastructural examination indicated that the acute phase of the induced mastitis was characterized by necrosis of secretory epithelium with a neutrophil, eosinophil, and macrophage response. Subsequently there was lymphoid infiltration, acinar involution, and fibrosis. This report confirms the pathogenicity of ureaplasma fo
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Monaghan, P., N. Perusinghe, G. Carlile, and W. H. Evans. "Rapid modulation of gap junction expression in mouse mammary gland during pregnancy, lactation, and involution." Journal of Histochemistry & Cytochemistry 42, no. 7 (1994): 931–38. http://dx.doi.org/10.1177/42.7.8014476.

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We investigated the expression of gap junctions in virgin, pregnant, lactating, and involuting mouse mammary gland epithelium with a panel of sequence-specific antibodies to connexins 26, 32, 40 and 43. Indirect immunofluorescence labeling of frozen sections of mammary gland showed that connexin26 was the major connexin in mammary epithelium. Connexins 43, 40, and 32 were not detected. Connexin26 was not detected in the mammary epithelium of virgin mice but was increasingly expressed during pregnancy. At Day 4 of pregnancy, when the mammary gland was composed almost exclusively of ducts, low l
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Watson, Christine J. "Post-lactational mammary gland regression: molecular basis and implications for breast cancer." Expert Reviews in Molecular Medicine 8, no. 32 (2006): 1–15. http://dx.doi.org/10.1017/s1462399406000196.

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During pregnancy, there is a massive increase in the number of luminal epithelial cells in the breast, which are destined to become the milk factories after birth. These cells are no longer required when the young are weaned, and are removed in a carefully orchestrated event called involution. In this process, the secretory epithelial cells die and are replaced by adipocytes, which redifferentiate as the epithelium is removed. It is essential that the gland is properly remodelled to a pre-pregnant state so that successful lactation can occur following a subsequent pregnancy. Furthermore, failu
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Rieanrakwong, Duangjai, Titaree Laoharatchatathanin, Ryota Terashima, et al. "Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats." Endocrinology 157, no. 7 (2016): 2750–58. http://dx.doi.org/10.1210/en.2016-1180.

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It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlacta
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Gangi, Lisa, Garrison Owens, Robin Humphreys, Lothar Hennighausen, and Edison Liu. "Mammary gland involution studies with cDNA microarrays." Nature Genetics 23, S3 (1999): 46. http://dx.doi.org/10.1038/14308.

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RYON, Joel, Lee BENDICKSON, and Marit NILSEN-HAMILTON. "High expression in involuting reproductive tissues of uterocalin/24p3, a lipocalin and acute phase protein." Biochemical Journal 367, no. 1 (2002): 271–77. http://dx.doi.org/10.1042/bj20020026.

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During reproduction the mass and number of cells in the uterus and the mammary gland increase rapidly and then diminish more rapidly after their reproductive functions are completed. The diminishment of tissue mass, known as involution, involves an ordered series of events that includes apoptosis of resident cells, neutrophil invasion, the release of degradative enzymes and phagocytosis of cellular debris. Local signals are believed to regulate the progression of involution in each tissue. Here we show that the mammary gland and uterus express high levels of uterocalin, a protein that specific
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Li, Xiangdong, Anni Wärri, Sari Mäkelä, et al. "Mammary Gland Development in Transgenic Male Mice Expressing Human P450 Aromatase." Endocrinology 143, no. 10 (2002): 4074–83. http://dx.doi.org/10.1210/en.2002-220181.

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Abstract We recently generated a transgenic mouse strain that expresses the human aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown that in these mice the serum estradiol concentration is highly elevated, whereas the testosterone concentration is decreased. In the present study we examined mammary gland development in AROM+ male mice at different ages and found that the mammary glands of AROM+ males undergo ductal and alveolar development morphologically resembling that of terminally differentiated female mammary glands, expressing mRNA for a milk protein gene (β-
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Stibbards-Lyle, Maya, Kristina Rinker, Laura Hall, Seleem Badawy, and Kathy Zhan. "Abstract PO4-24-05: Fluid forces and hormone levels during mammary gland development drive changes in breast epithelium that are relevant to the progression of postpartum breast cancer." Cancer Research 84, no. 9_Supplement (2024): PO4–24–05—PO4–24–05. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-24-05.

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Abstract Postpartum breast cancer (PPBC), diagnosed in the 5-10 years after childbirth, has an elevated risk of metastasis and death. Poor outcomes are thought to be due to factors involved in mammary gland involution, an important stage of mammary gland development. Involution functions to return the mammary gland to the normal post-lactation state and involves activation of multiple processes such as inflammation, wound healing, and lymphangiogenesis. Previously, these processes have been linked to mechanical forces induced by fluid flowing past cells, known as fluid shear stress (FSS). We a
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Pai, Vaibhav P., Laura L. Hernandez, Malinda A. Stull, and Nelson D. Horseman. "The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function." BioMed Research International 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/364746.

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Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a signif
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Boutinaud, M., JH Shand, MA Park, et al. "A quantitative RT-PCR study of the mRNA expression profile of the IGF axis during mammary gland development." Journal of Molecular Endocrinology 33, no. 1 (2004): 195–207. http://dx.doi.org/10.1677/jme.0.0330195.

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We have used quantitative RT-PCR to analyse the mRNA expression profile of the major components of the IGF axis in different stages of murine mammary gland development, including late pregnancy, lactation and involution. We have shown that all the genes studied, IGF-I, IGF-II, IGF receptor (IGFR) and IGF-binding protein (IGFBP)-1 to -6, were expressed in every stage, albeit at greatly differing levels and displaying unique expression profiles between developmental stages. IGF-I was always expressed at significantly higher levels than either IGF-II or IGFR. This suggests that IGF-I may be the m
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Ramaswamy, Bhuvaneswari, Neelam Shinde, Morgan Bauer, et al. "Abstract P5-01-08: Mechanistic differences between abrupt and gradual involution of mouse mammary gland." Cancer Research 82, no. 4_Supplement (2022): P5–01–08—P5–01–08. http://dx.doi.org/10.1158/1538-7445.sabcs21-p5-01-08.

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Abstract Objective: Epidemiological studies indicate a direct relation between length of breast feeding and protection against risk of triple negative breast cancer (TNBC), an aggressive subtype. While prolonged breastfeeding allows gradual involution (GI) of the breast, short-term or no breast feeding leads to abrupt involution (AI). We modelled AI and GI of breast in mice, and showed that mice subjected to GI have better protection from tissue remodeling associated injuries in the mammary gland. Our data revealed late development of ductal hyperplasia aided by pro-tumorigenic microenvironmen
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Nishikage, Mami, Yumiko Tateoka, and Fuyuki Itani. "Effectiveness of Onigirishibori Asa Self-care Technique for Weaning: A Study Using Intra Breast Ultrasound Imaging." International Journal of Medical Science and Health Research 08, no. 06 (2024): 40–48. https://doi.org/10.51505/ijmshr.2024.8604.

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Objective: To anatomically verify the effectiveness of the “compression (onigirishibori)” methods of the breast for weaning from breastfeeding for mammary gland involution using intramammary ultrasound images. Results: This observational, prospective, longitudinal study was conducted from June2020to July December 2023 and included 13 mothers who had decided to wean. We assigned them to the onigirishibori (n=9) and manual milking groups (n=4). The thickness of the mammary cavity was longitudinally observed from the day before weaning until 30 days after weaning. Ultrasound images revealed that
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Plath-Gabler, A., C. Gabler, F. Sinowatz, B. Berisha, and D. Schams. "The expression of the IGF family and GH receptor in the bovine mammary gland." Journal of Endocrinology 168, no. 1 (2001): 39–48. http://dx.doi.org/10.1677/joe.0.1680039.

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To study the involvement of the IGFs in mammary development and lactation of the cow, the temporal expressions of IGF-I and -II, its receptor type 1 (IGFR-1), IGF-binding proteins (IGFBPs)-1 to -6 and GH receptor (GHR) mRNA were examined. This was carried out for different stages of mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland of 26 animals. Furthermore, IGF-I was localised by immunohistochemistry. The highest mRNA concentrations for IGF-I were detected in the mammary tissue of late pregnant heifers (days 255-272) and significantly lower expression was
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Chakraborty, Moumita, and Michal Hershfinkel. "Zinc Signaling in the Mammary Gland: For Better and for Worse." Biomedicines 9, no. 9 (2021): 1204. http://dx.doi.org/10.3390/biomedicines9091204.

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Zinc (Zn2+) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn2+ is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn2+ accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly,
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Plath, A., R. Einspanier, F. Peters, F. Sinowatz, and D. Schams. "Expression of transforming growth factors alpha and beta-1 messenger RNA in the bovine mammary gland during different stages of development and lactation." Journal of Endocrinology 155, no. 3 (1997): 501–11. http://dx.doi.org/10.1677/joe.0.1550501.

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It is now widely accepted that the mammary gland is under interconnected hormonal and local control. Growth factors are involved in the intercellular signalling of the gland. Our aim was the detection of transforming growth factors alpha (TGF-alpha) and beta 1 (TGF-beta 1) messenger RNA during mammogenesis, lactogenesis, galactopoiesis and involution in the bovine mammary gland (total n = 27). During these stages the RNA was assessed by means of ribonuclease protection assay and reverse transcription-polymerase chain reaction (RT-PCR). To study possible influences of oestrogen, progesterone an
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Nguyen, A. V., and J. W. Pollard. "Transforming growth factor beta3 induces cell death during the first stage of mammary gland involution." Development 127, no. 14 (2000): 3107–18. http://dx.doi.org/10.1242/dev.127.14.3107.

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Involution of the mammary gland following weaning is divided into two distinct phases. Initially, milk stasis results in the induction of local factors that cause apoptosis in the alveolar epithelium. Secondly after a prolonged absence of suckling, the consequent decline in circulating lactogenic hormone concentrations initiates remodeling of the mammary gland to the virgin-like state. We have shown that immediately following weaning TGFbeta3 mRNA and protein is rapidly induced in the mammary epithelium and that this precedes the onset of apoptosis. Unilateral inhibition of suckling and hormon
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Zaragozá, R., E. R. García-Trevijano, V. J. Miralles, et al. "Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland." Biochemical Society Transactions 33, no. 6 (2005): 1397–98. http://dx.doi.org/10.1042/bst0331397.

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GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.
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Watson, Christine J., and Peter A. Kreuzaler. "Remodeling mechanisms of the mammary gland during involution." International Journal of Developmental Biology 55, no. 7-8-9 (2011): 757–62. http://dx.doi.org/10.1387/ijdb.113414cw.

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Sutherland, Kate D., Geoffrey J. Lindeman, and Jane E. Visvader. "The Molecular Culprits Underlying Precocious Mammary Gland Involution." Journal of Mammary Gland Biology and Neoplasia 12, no. 1 (2007): 15–23. http://dx.doi.org/10.1007/s10911-007-9034-8.

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Stein, Torsten, Nathan Salomonis, and Barry A. Gusterson. "Mammary Gland Involution as a Multi-step Process." Journal of Mammary Gland Biology and Neoplasia 12, no. 1 (2007): 25–35. http://dx.doi.org/10.1007/s10911-007-9035-7.

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