BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse.
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.
Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
Cheung Kwan
CK
Yeung
Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.|Chinese Medicine College, Jinan University, Guangzhou 510632, China.
Guang
G
Wang
Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
Yao
Y
Yao
Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.|Chinese Medicine College, Jinan University, Guangzhou 510632, China.
Jianxin
J
Liang
Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
Cheuk Yiu
CY
Tenny Chung
Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, UK.
Manli
M
Chuai
Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
Kenneth Ka Ho
KK
Lee
Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
Xuesong
X
Yang
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D005260:Female; D005496:Follicular Atresia / Q000378:metabolism* / Q000502:physiology; D006107:Granulosa Cells / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D006080:Ovarian Follicle / Q000378:metabolism* / Q000502:physiology; D010053:Ovary / Q000378:metabolism*
C484261:Babam2 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins