TY - JOUR
T1 - BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse
AU - Yeung, Cheung Kwan
AU - Wang, Guang
AU - Yao, Yao
AU - Liang, Jianxin
AU - Tenny Chung, Cheuk Yiu
AU - Chuai, Manli
AU - Lee, Kenneth Ka Ho
AU - Yang, Xuesong
N1 - This study was supported by NSFC grant (81571436, 31300963 and 31401230), Science and Technology Planning Project of Guangdong Province (2016B030229002, 2014A020213008 and 2014A020221091), Science and Technology Program of Guangzhou (201510010073 and 201710010054), Guangdong Natural Science Foundation (2016A030311044), General Research Grant (14100315), and Research Grant of Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University (ZSYX-M-00001 and ZSYX-T-00001).
PY - 2017/3/23
Y1 - 2017/3/23
N2 - The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage. There was a reduction in follicles number of BRE mutant (BRE(-/-)) mice. It was attributed to increase the follicular atresia in ovaries, as a result of retarded follicular development. We established that cell proliferation was inhibited, while apoptosis was markedly increased in the granulosa cells in the absence of BRE. In addition, expressions of γ-H2AX (marker for showing DNA double-strand breaks) and DNA damage-relevant genes are both upregulated in BRE(-/-) mice. In sum, these results suggest that the absence of BRE, deficiency in DNA damage repair, causes increased apoptosis in granulosa cells, which in turn induces follicular atresia in BRE(-/-) mice.
AB - The BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage. There was a reduction in follicles number of BRE mutant (BRE(-/-)) mice. It was attributed to increase the follicular atresia in ovaries, as a result of retarded follicular development. We established that cell proliferation was inhibited, while apoptosis was markedly increased in the granulosa cells in the absence of BRE. In addition, expressions of γ-H2AX (marker for showing DNA double-strand breaks) and DNA damage-relevant genes are both upregulated in BRE(-/-) mice. In sum, these results suggest that the absence of BRE, deficiency in DNA damage repair, causes increased apoptosis in granulosa cells, which in turn induces follicular atresia in BRE(-/-) mice.
U2 - 10.1038/cddis.2017.91
DO - 10.1038/cddis.2017.91
M3 - Article
C2 - 28333135
SN - 2041-4889
VL - 8
SP - 1
EP - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
M1 - e2697
ER -