Dataset Information

Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice.

ABSTRACT: As a member of the POU (Pit-Oct-Unc) transcription factor family, OCT4 (Octamer-binding transcription factor 4) is associated with the cellular proliferative. However, the roles of OCT4 in regulating the transition from preantral follicle to early antral follicle are still remains unclear. To evaluate the effect of OCT4 on cellular development in ovary, mice were injected with eCG in vivo or granulosa cells were co-cultured with FSH in vitro. The results showed that eCG up-regulated ovarian OCT4 expression. Meanwhile, OCT4 expression in granulosa cells was also up-regulated by FSH, and knockdown of OCT4 by siRNA significantly decreased FSH-induced cellular viability. Moreover, gonadotropin increased p-GSK3? (Glycogen synthase kinase 3-beta) level, ?-catenin expression and its translocation to nuclear in ovarian cells. In addition, the inhibition of GSK3? activity by CT99021 significantly increased the expression of ?-catenin and OCT4 in granulosa cells. And knockdown ?-catenin by siRNA dramatically abolished FSH-induced OCT4 expression and cellular development. Furthermore, FSH-induced the phosphorylation of GSK3?, expression of ?-catenin and OCT4, and translocation of ?-catenin were mediated by the PI3K/Akt pathway. Taken together, the present study demonstrates that FSH regulated OCT4 expression via GSK3?/?-catenin pathway, which was mediated by the PI3K/Akt pathway. And these regulations are involved in ovarian cell development.

SUBMITTER: Heng D

PROVIDER: S-EPMC6966609 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice.

Heng Dai D Wang Qiaozhi Q Ma Xiaoshu X Tian Ye Y Xu Kaili K Weng Xuechun X Hu Xusong X Liu Wenbo W Zhang Cheng C

Frontiers in endocrinology 20200110

As a member of the POU (Pit-Oct-Unc) transcription factor family, OCT4 (Octamer-binding transcription factor 4) is associated with the cellular proliferative. However, the roles of OCT4 in regulating the transition from preantral follicle to early antral follicle are still remains unclear. To evaluate the effect of OCT4 on cellular development in ovary, mice were injected with eCG <i>in vivo</i> or granulosa cells were co-cultured with FSH <i>in vitro</i>. The results showed that eCG up-regulate ...[more]

PMID: 31998243

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Project description:Study questionIs the genome-wide response of human cumulus cells to FSH and insulin-like growth factors (IGFs) comparable to the response observed in undifferentiated granulosa cells (GCs)?Summary answerFSH actions in human cumulus cells mimic those observed in preantral undifferentiated GCs from laboratory animals, and approximately half of the regulated genes are dependent on the simultaneous activation of the IGF1 receptor (IGF1R).What is known alreadyAnimal studies have shown that FSH and the IGFs system are required for follicle growth and maturation. In humans, IGF levels in the follicular fluid correlate with patients' responses to IVF protocols. The main targets of FSH and IGFs in the ovary are the GCs; however, the genomic mechanisms involved in the response of GCs to these hormones are unknown.Study design, size, durationHuman cumulus cells isolated from IVF patients were cultured for 48 h in serum-free media in the presence of vehicle, FSH, IGF1R inhibitor or their combination.Participants/materials, setting, methodsDiscarded cumulus cells were donated to research by reproductive-aged women undergoing IVF due to non-ovarian etiologies of infertility at a university-affiliated clinic. The effect of FSH and/or IGF1R inhibition on cumulus cell function was evaluated using Affymetrix microarrays, quantitative PCR, western blot, promoter assays and hormone level measurements.Main results and the role of chanceThe findings demonstrate that human cumulus cells from IVF patients respond to FSH with the expression of genes known to be markers of the preantral to preovulatory differentiation of GCs. These results also demonstrate that ~50% of FSH-regulated genes require IGF1R activity and suggest that several aspects of follicle growth are coordinately regulated by FSH and IGFs in humans. This novel approach will allow for future mechanistic and molecular studies on the regulation of human follicle maturation.Large scale dataData set can be accessed at Gene Expression Omnibus number GSE86427.Limitations, reasons for cautionExperiments were performed using primary human cumulus cells. This may not represent the response of intact follicles.Wider implications of the findingsUnderstanding the mechanisms involved in the regulation of GC differentiation by FSH and IGF in humans will contribute to improving treatments for infertility.Study funding/competing interest(s)The project was financed by the National Instituted of Health grant number R56HD086054 and R01HD057110 (C.S.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare.

Project description:Anti-Mullerian hormone (AMH) is an important reproductive marker of ovarian reserve produced by granulosa cells (GCs) of pre-antral and early-antral ovarian follicles in several species, including cattle. This hormone plays a vital role during the recruitment of primordial follicles and follicle stimulating hormone (FSH)-dependent follicular growth. However, the regulatory mechanism of AMH expression in follicles is still unclear. In this study, we compared the expression of AMH, AMHR-II, BMP2, BMP6, FSHR, and LHCGR genes during follicular development. In-vitro expression study was performed with and without FSH for AMH, AMHR-II, BMP2, and BMP6 genes in bovine GCs which were isolated from 3-8 mm follicles. Association among the mRNA expression and hormone level was estimated. GCs were collected from small (3-8 mm), medium (9-12 mm) and large size (13 to 24 mm) follicles before, during onset, and after deviation, respectively. Further, mRNA expression, hormones (AMH, FSH, and LH), apoptosis of GCs, and cell viability were detected by qRT-PCR, ELISA, flow cytometry, and spectrophotometry. AMH, AMHR-II, BMP2, and FSHR genes were highly expressed in small and medium follicles as compared to large ones. In addition, the highest level of AMH protein (84.14 ± 5.41 ng/mL) was found in medium-size follicles. Lower doses of FSH increased the viability of bovine GCs while higher doses repressed them. In-vitro cultured GCs treated with FSH significantly increased the AMH, AMHR-II, and BMP2 expression levels at lower doses, while expression levels decreased at higher doses. We found an optimum level of FSH (25 ng/mL) which can significantly enhance AMH and BMP2 abundance (p < 0.05). In summary, AMH, AMHR-II, and BMP2 genes showed a higher expression in follicles developed in the presence of FSH. However, lower doses of FSH demonstrated a stimulatory effect on AMH and BMP2 expression, while expression started to decline at the maximum dose. In this study, we have provided a better understanding of the mechanisms regulating AMH, AMHR II, and BMP2 signaling in GCs during folliculogenesis, which would improve the outcomes of conventional assisted reproductive technologies (ARTs), such as superovulation and oestrus synchronization in bovines.

Dataset Information

Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice.

Publications

Role of OCT4 in the Regulation of FSH-Induced Granulosa Cells Growth in Female Mice.

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