HDAC3 maintains oocyte meiosis arrest by repressing amphiregulin expression before the LH surge

Huarong Wang, Han Cai, Xiao Wang, Meiling Zhang, Bingying Liu, Ziqi Chen, Tingting Yang, Junshun Fang, Yanhao Zhang, Wei Liu, Jun Han, Qirui Guo, Hua Zhang, Haibin Wang, Guoliang Xia and Chao Wang ()
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Huarong Wang: China Agricultural University
Han Cai: Medical College of Xiamen University
Xiao Wang: China Agricultural University
Meiling Zhang: Shanghai Jiao Tong University
Bingying Liu: China Agricultural University
Ziqi Chen: China Agricultural University
Tingting Yang: China Agricultural University
Junshun Fang: China Agricultural University
Yanhao Zhang: China Agricultural University
Wei Liu: China Agricultural University
Jun Han: China Agricultural University
Qirui Guo: China Agricultural University
Hua Zhang: China Agricultural University
Haibin Wang: Medical College of Xiamen University
Guoliang Xia: China Agricultural University
Chao Wang: China Agricultural University

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammals, however, the detailed molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge-induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediate recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.

Date: 2019
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DOI: 10.1038/s41467-019-13671-8

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