LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62. Issue 3 (19th February 2020)

• Record Type: Journal Article
• Authors: He, Meina; Zhang, Tuo; Zhu, Zijian; Qin, Shaogang; Wang, Huarong; Zhao, Lihua; Zhang, Xinran; Hu, Jiayi; Wen, Jia; Cai, Han; Xin, Qiliang; Guo, Qirui; Lin, Lin; Zhou, Bo; Zhang, Hua; Xia, Guoliang; Wang, Chao
• Is Part Of: Aging cell. Volume 19:Issue 3(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-19
• Subjects: autophagy -- H3K4me2 -- LSD1 -- oocyte loss -- p62 -- primordial follicle pool; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13102
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine‐specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time‐specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice. Abstract : A diagram showing the function and regulation mechanism of LSD1 during primordial follicle formation. LSD1 regulates the transcription of autophagy adaptor and substate p62 by its H3K4me2 demethylase activity.