首页|LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells

LSD1 promotes the FSH responsive follicle formation by regulating autophagy and repressing Wt1 in the granulosa cells

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In a growing follicle,the survival and maturation of the oocyte largely depend on support from somatic cells to facilitate FSH-induced mutual signaling and chemical communication.Although apoptosis and autophagy in somatic cells are involved in the process of FSH-induced follicular development,the under-lying mechanisms require substantial study.According to our study,along with FSH-induced antral fol-licles(AFs)formation,both lysine-specific demethylase 1(LSD1)protein levels and autophagy increased simultaneously in granulosa cells(GCs)in a time-dependent manner,we therefore evaluated the impor-tance of LSD1 upon facilitating the formation of AFs correlated to autophagy in GCs.Conditional knockout of Lsd1 in GCs resulted in significantly decreased AF number and subfertility in females,accompanied by marked suppression of the autophagy in GCs.On the one hand,depletion of Lsd1 resulted in accumulation of Wilms tumor 1 homolog(WT1),at both the protein and mRNA levels,WT1 prevented the expression of FSH receptor(Fshr)in GCs and thus reduced the responsiveness of the secondary follicles to FSH induc-tion.On the other hand,depletion of LSD1 resulted in suppressed level of autophagy by upregulation of ATG16L2 in GCs.We finally approved that LSD1 contributed to these sequential activities in GCs through its H3K4me2 demethylase activity.Therefore,the importance of LSD1 in GCs is attributable to its roles in both accelerating autophagy and suppressing WT1 expression to ensure the responsiveness of GCs to FSH during AFs formation.

LSD1AutophagyH3K4me2WT1Follicle formationFollicle stimulating hormone

Zijian Zhu、Meina He、Tuo Zhang、Ting Zhao、Shaogang Qin、Meng Gao、Wenji Wang、Wenying Zheng、Ziqi Chen、Longping Liu、Ming Hao、Bo Zhou、Hua Zhang、Jianbin Wang、Fengchao Wang、Guoliang Xia、Chao Wang

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State Key Laboratory of Farm Animal Biotech Breeding,College of Biological Sciences,China Agricultural University,Beijing 100193,China

College of Basic Medicine,Guizhou Medical University,Guiyang 550025,China

Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases,Department of Physiology,College of Basic Medicine,Guizhou Medical University,Guiyang 550025,China

School of Life Sciences,Taizhou University,Taizhou 318000,China

School of Life Sciences,Tsinghua University,Beijing 100084,China

Transgenic Animal Center,National Institute of Biological Sciences,Beijing 102206,China

Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western China,College of Life Science,Ningxia University,Yinchuan 750021,China

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National Key Research & Developmental Program of ChinaNational Key Research & Developmental Program of ChinaNational Key Research & Developmental Program of ChinaNational Key Research & Developmental Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationInstitution of Higher Education Projects of Building Firstclass Discipline Construction in Ningxia Region(Biology)Doctoral Startup Foundation of Guizhou Medical University

2022YFC27038032018YFC10037002018YFC10038012023YFD1300501320711323187279232270904320708393210091382260291321006862021M700972NXYLXK2017B05[2020]038

2024

10.1016/j.scib.2024.01.015

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(8)
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