Chen Haixia, Li Peng, Du Xiaoling, Zhao Yiding, Wang Lingling, Tian Ye, Song Xueru, Shuai Ling, Bai Xiaohong, Chen Lingyi
Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Union Medical Center, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Frontiers Science Center for Cell Responses, National Demonstration Center for Experimental Biology Education and College of Life Sciences, Nankai University, Institute of Translational Medicine, Tianjin, China.
Front Cell Dev Biol. 2022 Apr 25;10:850052. doi: 10.3389/fcell.2022.850052. eCollection 2022.
The gene has been associated with male infertility. Male chimera mice were infertile, supporting the prevailing view that haploinsufficiency causes male infertility. In this study, we identified a heterozygous mutation on , 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 in FF and oocyte activation, we constructed knockout mice. Surprisingly, male mice, but not 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 sperm, indicating that FF caused by male deficiency is overcome by AOA. Mechanistically, loss of PLCζ around the acrosome might be the reason for FF of sperm. Taken together, our data indicated that homozygous knockout of , but not haploinsufficiency, leads to male infertility and FF.
该基因与男性不育有关。雄性嵌合体小鼠不育，支持了单倍剂量不足导致男性不育的主流观点。在本研究中，我们在一对患者夫妇的男性伴侣中鉴定出 上的一个杂合突变，c.72C>A（p.Cys24Ter），这对夫妇之前在卵胞浆内单精子注射（ICSI）后受精失败（FF），而在ICSI联合人工卵母细胞激活（AOA）后成功怀孕。为了研究 在FF和卵母细胞激活中的作用，我们构建了 基因敲除小鼠。令人惊讶的是， 雄性小鼠而非 雄性小鼠不育，精子数量减少且精子形态异常。重要的是，AOA处理提高了注射 精子的ICSI胚胎的2细胞胚胎率，表明由男性 缺陷引起的FF可被AOA克服。从机制上讲，顶体周围PLCζ的缺失可能是 精子FF的原因。综上所述，我们的数据表明， 的纯合敲除而非单倍剂量不足会导致男性不育和FF。
