Dataset Information

Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.

ABSTRACT: It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose-dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy-related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c-Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time-dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (T?RII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGF?) pathway.

SUBMITTER: Zhang D

PROVIDER: S-EPMC4364840 | biostudies-other | 2015 Apr

REPOSITORIES: biostudies-other

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Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.

Zhang Dan D Li Jingyi J Xu Gufeng G Zhang Runjv R Zhou Chengliang C Qian Yeqing Y Liu Yifeng Y Chen Luting L Zhu Bo B Ye Xiaoqun X Qu Fan F Liu Xinmei X Shi Shuai S Yang Weijun W Sheng Jianzhong J Huang Hefeng H

Aging cell 20141113 2

It is widely believed that endometrial atrophy in postmenopausal women is due to an age-related reduction in estrogen level. But the role of high circulating follicle-stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post-OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin-releasing hormone agonist (GnRHa). In vitr ...[more]

PMID: 25393561

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Project description:17?-estradiol (E2) is an important sex steroid produced by ovary and brain. In mammals, E2 plays an important role in hypothalamus-pituitary-gonad axis to regulate puberty onset, however, little is known about the functional role of E2 in teleost pituitary. Using prepubertal grass carp as model, three nuclear estrogen receptors (nERs: estrogen receptor alpha, estrogen receptor beta 1, and estrogen receptor beta 2) and two G protein-coupled estrogen receptors (GPER1: GPER1a and GPER1b) were isolated from grass carp pituitary. Tissue distribution analysis indicated that both nERs and GPERs were highly detected in grass carp pituitary, which suggested that E2 should play an important role in grass carp pituitary. Using primary cultured grass carp pituitary cells as model, high-throughput RNA-seq was used to examine the E2-induced differentially expressed genes (DEGs). Transcriptomic analysis showed that E2 could significantly upregulate the expression of 28 genes in grass carp pituitary cells, which were characterized into different functions including reproduction, gonad development, and central nervous system development. Further studies confirmed that E2 could induce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and mRNA expression in prepubertal grass carp pituitary in vivo and in vitro. In the pituitary, LH and FSH regulation by E2 were mediated by both ER? and GPER1. Apparently, E2-induced LH? and FSH? mRNA expression were mediated by adenylyl cyclase/cAMP/protein kinase A, phospholipase C/inositol 1,4,5-triphosphate/protein kinase C, and Ca2+/calmodulin/CaM-dependent protein kinase II pathways. In addition to LH and FSH, E2 could also induce growth regulation by estrogen in breast cancer 1 (a novel regulator for pituitary development) mRNA expression in grass carp pituitary cells. These results, as a whole, suggested that E2 could play an important role in gonadotropin hormone release and pituitary development in prepubertal grass carp.

Project description:BackgroundPreviously, we reported a model for assessing ovarian reserves using 4 predictors: anti-Müllerian hormone (AMH) level, antral follicle count (AFC), follicle-stimulating hormone (FSH) level, and female age. This model is referred as the AAFA (anti-Müllerian hormone level-antral follicle count-follicle-stimulating hormone level-age) model.ObjectiveThis study aims to explore the possibility of establishing a model for predicting ovarian reserves using only 3 factors: AMH level, FSH level, and age. The proposed model is referred to as the AFA (anti-Müllerian hormone level-follicle-stimulating hormone level-age) model.MethodsOocytes from ovarian cycles stimulated by gonadotropin-releasing hormone antagonist were collected retrospectively at our reproductive center. Poor ovarian response (<5 oocytes retrieved) was defined as an outcome variable. The AFA model was built using a multivariable logistic regression analysis on data from 2017; data from 2018 were used to validate the performance of AFA model. Measurements of the area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predicative value were used to evaluate the performance of the model. To rank the ovarian reserves of the whole population, we ranked the subgroups according to the predicted probability of poor ovarian response and further divided the 60 subgroups into 4 clusters, A-D, according to cut-off values consistent with the AAFA model.ResultsThe AUCs of the AFA and AAFA models were similar for the same validation set, with values of 0.853 (95% CI 0.841-0.865) and 0.850 (95% CI 0.838-0.862), respectively. We further ranked the ovarian reserves according to their predicted probability of poor ovarian response, which was calculated using our AFA model. The actual incidences of poor ovarian response in groups from A-D in the AFA model were 0.037 (95% CI 0.029-0.046), 0.128 (95% CI 0.099-0.165), 0.294 (95% CI 0.250-0.341), and 0.624 (95% CI 0.577-0.669), respectively. The order of ovarian reserve from adequate to poor followed the order from A to D. The clinical pregnancy rate, live-birth rate, and specific differences in groups A-D were similar when predicted using the AFA and AAFA models.ConclusionsThis AFA model for assessing the true ovarian reserve was more convenient, cost-effective, and objective than our original AAFA model.

Dataset Information

Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.

Publications

Follicle-stimulating hormone promotes age-related endometrial atrophy through cross-talk with transforming growth factor beta signal transduction pathway.

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