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  3. EZH1/2 plays critical roles in oocyte meiosis prophase I in mice

EZH1/2 plays critical roles in oocyte meiosis prophase I in mice

  • Biol Res. 2024 Nov 8;57(1):83. doi: 10.1186/s40659-024-00564-4.
Ting Jiang 1,  Chengxiu Zhang 1,  Xinjing Cao 1,  Yingpu Tian 1,  Han Cai 2,  Shuangbo Kong 2,  Jinhua Lu 2,  Haibin Wang 3 4,  Zhongxian Lu 5 6 7
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361005, China.
  • 2 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, China.
  • 3 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, China. haibin.wang@vip.163.com.
  • 4 Medical College of Xiamen University, Xiamen, Fujian, 361102, China. haibin.wang@vip.163.com.
  • 5 School of Pharmaceutical Sciences, Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiamen, Fujian, 361005, China. zhongxian@xmu.edu.cn.
  • 6 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, 361102, China. zhongxian@xmu.edu.cn.
  • 7 School of Pharmaceutical Sciences, Xiamen University, Zhuangjin Hall, Room 363, Xiamen, Fujian, 361102, China. zhongxian@xmu.edu.cn.
PMID: 39511641 DOI: 10.1186/s40659-024-00564-4
Abstract

Backgroud: abnormalities or defects in oocyte meiosis can result in decreased oocyte quality, reduced ovarian reserve, and female diseases. However, the mechanisms of oocyte meiosis remain largely unknown, especially epigenetic regulation. Here, we explored the role of EZH1/2 (Histone Methyltransferase of H3K27) in mouse oocyte meiosis by inhibiting its activity and deleting its gene.

Results: with embryonic ovary cultured in vitro, EZH1/2 was demonstrated to be essential for oocyte development during meiosis prophase I in mice. Activity inhibition or gene knockout of EZH1/2 resulted in cell Apoptosis and a reduction in oocyte numbers within embryonic ovaries. By observing the expression of some meiotic marker protein (γ-H2AX, diplotene stage marker MSY2 and synapsis complex protein SCP1), we found that function deficiency of EZH1/2 resulted in failure of DNA double-strand breaks (DSBs) repair and break of meiotic progression in fetal mouse ovaries. Moreover, EZH1/2 deficiency led to the suppression of ATM (Ataxia Telangiectasia Mutated kinase) phosphorylation and a decrease in the expression of key DNA repair proteins Hormad1, Mre11, Rad50, and Nbs1 in fetal mouse ovaries, underscoring the enzyme's pivotal role in initiating DNA repair. RNA-seq analysis revealed that EZH1/2-deletion induced abnormal expression of multiple genes involved into several function of oocyte development in embryonic ovaries. Knockout of EZH1/2 in ovaries also affected the levels of H3K9me3 and H4K20me2, as well as the expression of their target genes L3mbtl4 and Fbxo44.

Conclusions: our study demonstrated that EZH1/2 plays a role in the DSBs repair in oocyte meiosis prophase I via multiple mechanisms and offers new insights into the physiological regulatory role of histone modification in fetal oocyte guardianship and female fertility.

Keywords

DSBs repair; EZH1; EZH2; Embryonic ovary; Oocyte meiosis.

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