scholarly journals PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Min Chen ◽  
Fangfang Dong ◽  
Min Chen ◽  
Zhiming Shen ◽  
Haowei Wu ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Cell Lineage ◽  
Arginine Methylation ◽  
Major Type ◽  
Follicle Development ◽  
Ovarian Follicle Development ◽  
High Level

Protein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found that PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate that PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

scholarly journals PRMT5 regulates ovarian follicle development by facilitating Wt1 translation

2021 ◽  
Author(s):  
Min Chen ◽  
Fangfang Dong ◽  
Min Chen ◽  
Zhiming Shen ◽  
Haowei Wu ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Cell Lineage ◽  
Arginine Methylation ◽  
Major Type ◽  
Follicle Development ◽  
Ovarian Follicle Development ◽  
High Level

AbstractProtein arginine methyltransferase 5 (Prmt5) is the major type II enzyme responsible for symmetric dimethylation of arginine. Here, we found PRMT5 was expressed at high level in ovarian granulosa cells of growing follicles. Inactivation of Prmt5 in granulosa cells resulted in aberrant follicle development and female infertility. In Prmt5-knockout mice, follicle development was arrested with disorganized granulosa cells in which WT1 expression was dramatically reduced and the expression of steroidogenesis-related genes was significantly increased. The premature differentiated granulosa cells were detached from oocytes and follicle structure was disrupted. Mechanism studies revealed that Wt1 expression was regulated by PRMT5 at the protein level. PRMT5 facilitated IRES-dependent translation of Wt1 mRNA by methylating HnRNPA1. Moreover, the upregulation of steroidogenic genes in Prmt5-deficient granulosa cells was repressed by Wt1 overexpression. These results demonstrate PRMT5 participates in granulosa cell lineage maintenance by inducing Wt1 expression. Our study uncovers a new role of post-translational arginine methylation in granulosa cell differentiation and follicle development.

scholarly journals Yes-associated protein (YAP) is required in maintaining normal ovarian follicle development and function

2018 ◽  
Author(s):  
Michele R. Plewes ◽  
Xiaoying Hou ◽  
Pan Zhang ◽  
Jennifer Wood ◽  
Andrea Cupp ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Hippo Pathway ◽  
Critical Role ◽  
Ovarian Follicles ◽  
Follicle Development ◽  
Hippo Signaling ◽  
Ovarian Follicle Development ◽  
The Hippo Pathway

ABSTRACTYes-associated protein (YAP) is one of the major components of the Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway. Although the exact extracellular signal that controls the Hippo pathway is currently unknown, increasing evidence supports a critical role of the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. The ovary is one of few adult tissues that exhibit cyclical changes. Ovarian follicles, the basic units of ovary, are composed of a single oocyte surrounded by expanding layers of granulosa and theca cells. Granulosa cells (GCs) produce sex steroids and growth factors, which facilitate the development of the follicle and maturation of the oocyte. It has been reported that YAP is highly expressed in human GC tumors, but the role of YAP in normal ovarian follicle development is largely unknown. In current study, we examined YAP expression in bovine ovaries. We demonstrate that downstream hippo signaling effector protein, YAP and transcription co-activator, TAZ, are present and localization of both YAP and TAZ are density-dependent. Likewise, YAP and TAZ are critically involved in granulosa cell proliferation. Furthermore, reducing YAP in granulosa cells inhibits FSH-induced aromatase expression and estradiol biosynthesis. The data suggest that YAP plays an important role in the development of ovarian follicles and estradiol synthesis, which are necessary for maintaining normal ovarian function.

scholarly journals Notch Signaling Is Involved in Ovarian Follicle Development by Regulating Granulosa Cell Proliferation

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2437-2447 ◽  
Author(s):  
Chun-Ping Zhang ◽  
Jun-Ling Yang ◽  
Jun Zhang ◽  
Lei Li ◽  
Lin Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Notch Signaling ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Butyl Ester ◽  
Follicular Development ◽  
Follicle Development ◽  
Ovarian Follicle Development

Notch signaling is an evolutionarily conserved pathway, which regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Notch signaling are expressed in mammalian ovaries, but the exact functions of this pathway in follicle development is still unclear. In this study, primary follicles were cultured in vitro and treated with Notch signaling inhibitors, L-658,458 and N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). We found that the cultured follicles completely stopped developing after L-658,458 and DAPT treatment, most of the granulosa cells were detached, and the oocytes were also degenerated with condensed cytoplasma. Further studies demonstrated that the proliferation of granulosa cells was dependent on the Notch signaling. L-658,458 and DAPT treatment inhibited proliferation of in vitro cultured primary granulosa cells and decreased the expression of c-Myc. Lentivirus mediated overexpression of Notch intracellular domain 2, and c-Myc could promote the proliferation of granulosa cells and rescue the growth inhibition induced by L-658,458 and DAPT. In conclusion, Notch signaling is involved in follicular development by regulating granulosa cell proliferation.

scholarly journals Timely expression and activation of YAP1 in granulosa cells is essential for ovarian follicle development

2019 ◽  
Vol 33 (9) ◽  
pp. 10049-10064 ◽  
Author(s):  
Xiangmin Lv ◽  
Chunbo He ◽  
Cong Huang ◽  
Hongbo Wang ◽  
Guohua Hua ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Follicle Development ◽  
Ovarian Follicle Development

scholarly journals Involvement of miRNAs in equine follicle development

Reproduction ◽  
2013 ◽  
Vol 146 (3) ◽  
pp. 273-282 ◽  
Author(s):  
S N Schauer ◽  
S D Sontakke ◽  
E D Watson ◽  
C L Esteves ◽  
F X Donadeu
Keyword(s):  
Cell Survival ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Ovarian Follicle ◽  
Follicle Development ◽  
Previous Evidence ◽  
Ovarian Follicle Development ◽  
Fluid Levels ◽  
Follicle Selection

Previous evidence fromin vitrostudies suggests specific roles for a subset of miRNAs, including miR-21, miR-23a, miR-145, miR-503, miR-224, miR-383, miR-378, miR-132, and miR-212, in regulating ovarian follicle development. The objective of this study was to determine changes in the levels of these miRNAs in relation to follicle selection, maturation, and ovulation in the monovular equine ovary. In Experiment 1, follicular fluid was aspirated during ovulatory cycles from the dominant (DO) and largest subordinate (S) follicles of an ovulatory wave and the dominant (DA) follicle of a mid-cycle anovulatory wave (n=6 mares). Follicular fluid levels of progesterone and estradiol were lower (P<0.01) in S follicles than in DO follicles, whereas mean levels of IGF1 were lower (P<0.01) in S and DA follicles than in DO follicles. Relative to DO and DA follicles, S follicles had higher (P≤0.01) follicular fluid levels of miR-145 and miR-378. In Experiment 2, follicular fluid and granulosa cells were aspirated from dominant follicles before (DO) and 24 h after (L) administration of an ovulatory dose of hCG (n=5 mares/group). Relative to DO follicles, L follicles had higher follicular fluid levels of progesterone (P=0.05) and lower granulosa cell levels ofCYP19A1andLHCGR(P<0.005). Levels of miR-21, miR-132, miR-212, and miR-224 were increased (P<0.05) in L follicles; this was associated with reduced expression of the putative miRNA targets,PTEN,RASA1, andSMAD4. These novel results may indicate a physiological involvement of miR-21, miR-145, miR-224, miR-378, miR-132, and miR-212 in the regulation of cell survival, steroidogenesis, and differentiation during follicle selection and ovulation in the monovular ovary.

scholarly journals SMAD3 regulates the diverse functions of rat granulosa cells relating to the FSHR/PKA signaling pathway

Reproduction ◽  
2013 ◽  
Vol 146 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Yexia Li ◽  
Yujie Jin ◽  
Yuxia Liu ◽  
Chunyan Shen ◽  
Jingxia Dong ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Transforming Growth Factor ◽  
Ovarian Follicle ◽  
Transforming Growth Factor Β ◽  
Female Rats ◽  
Nuclear Antigen ◽  
Follicle Development ◽  
Sprague Dawley ◽  
Ovarian Follicle Development ◽  
Estrogen Production

The function of Smad3, a downstream signaling protein of the transforming growth factor β (TGFβ) pathway, in ovarian follicle development remains to be elucidated. The effects of Smad3 on ovarian granulosa cells (GCs) in rat were studied. Female rats (21 days of age Sprague–Dawley) received i.p. injections of pregnant mare serum gonadotropin, and GCs were harvested for primary culture 48 h later. These cells were engineered to overexpress or knockdown Smad3, which were validated by immunohistochemistry and western blot. The expression of proliferating cell nuclear antigen (PCNA), cyclin D2, TGFβ receptor II (TGFβRII), protein kinase A (PKA), and FSH receptor (FSHR) was also detected by western blotting. Cell cycle and apoptosis of GCs were assayed by flow cytometry. The level of estrogen secreted by GCs was detected by ELISA. Smad3 overexpression promoted estrogen production and proliferation while inhibiting apoptosis of GCs. Reduction in Smad3 by RNAi resulted in reduced estrogen production and proliferation and increased apoptosis of GCs. Manipulation of Smad3 expression also resulted in changes in FSHR and PKA expression, suggesting that the effects of Smad3 on follicle development are related to FSHR-mediated cAMP signaling.

scholarly journals Wt1 functions in ovarian follicle development by regulating granulosa cell differentiation

2013 ◽  
Vol 23 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Fei Gao ◽  
Jun Zhang ◽  
Xiaona Wang ◽  
Junling Yang ◽  
Dahua Chen ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Granulosa Cell ◽  
Ovarian Follicle ◽  
Follicle Development ◽  
Ovarian Follicle Development

scholarly journals The Role of BMP Signalling Pathway in the Regulation of Ovarian Follicle Development.

2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 289-290
Author(s):  
Ghanim Almahbobi ◽  
Chantelle Ruoss ◽  
Amanda Tadros ◽  
Tim O'Shea ◽  
Jim McFarlane
Keyword(s):  
Ovarian Follicle ◽  
Signalling Pathway ◽  
Follicle Development ◽  
Ovarian Follicle Development ◽  
Bmp Signalling
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