Homozygous Loss of Septin12, but not its Haploinsufficiency, Leads to Male Infertility and Fertilization Failure

Author:

Chen Haixia,Li Peng,Du Xiaoling,Zhao Yiding,Wang Lingling,Tian Ye,Song Xueru,Shuai Ling,Bai Xiaohong,Chen Lingyi

Abstract

The SEPTIN12 gene has been associated with male infertility. Male Septin12+/− chimera mice were infertile, supporting the prevailing view that SEPTIN12 haploinsufficiency causes male infertility. In this study, we identified a heterozygous mutation on SEPTIN12, c.72C>A (p.Cys24Ter) in the male partner of a patient couple, who had a previous fertilization failure (FF) after intracytoplasmic sperm injection (ICSI) and became pregnant after ICSI together with artificial oocyte activation (AOA). To investigate the role of SEPTIN12 in FF and oocyte activation, we constructed Septin12 knockout mice. Surprisingly, Septin12−/− male mice, but not Septin12+/− male mice, are infertile, and have reduced sperm counts and abnormal sperm morphology. Importantly, AOA treatment enhances the 2-cell embryo rate of ICSI embryos injected with Septin12−/− sperm, indicating that FF caused by male Septin12 deficiency is overcome by AOA. Mechanistically, loss of PLCζ around the acrosome might be the reason for FF of Septin12−/− sperm. Taken together, our data indicated that homozygous knockout of Septin12, but not Septin12 haploinsufficiency, leads to male infertility and FF.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Natural Science Foundation of Tianjin City

Publisher

Frontiers Media SA

Subject

Cell Biology,Developmental Biology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Toward clinical exomes in diagnostics and management of male infertility;The American Journal of Human Genetics;2024-05

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