scholarly journals BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse

2017 ◽  
Vol 8 (3) ◽  
pp. e2697-e2697 ◽  
Author(s):  
Cheung Kwan Yeung ◽  
Guang Wang ◽  
Yao Yao ◽  
Jianxin Liang ◽  
Cheuk Yiu Tenny Chung ◽  
...  
1998 ◽  
Vol 140 (1-2) ◽  
pp. 15-18 ◽  
Author(s):  
Elizabeth A McGee ◽  
Sheau-Yu Hsu ◽  
Antti Kaipia ◽  
Aaron J.W. Hsueh

2013 ◽  
Vol 23 (2) ◽  
pp. 333-341 ◽  
Author(s):  
Fei Gao ◽  
Jun Zhang ◽  
Xiaona Wang ◽  
Junling Yang ◽  
Dahua Chen ◽  
...  

2021 ◽  
Author(s):  
Min Chen ◽  
Fangfang Dong ◽  
Min Chen ◽  
Zhiming Shen ◽  
Haowei Wu ◽  
...  

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.


Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2437-2447 ◽  
Author(s):  
Chun-Ping Zhang ◽  
Jun-Ling Yang ◽  
Jun Zhang ◽  
Lei Li ◽  
Lin Huang ◽  
...  

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.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Min Chen ◽  
Fangfang Dong ◽  
Min Chen ◽  
Zhiming Shen ◽  
Haowei Wu ◽  
...  

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.


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