Zhang Jingjing, Zhou Xinli, Wan Danyang, Yu Li, Chen Xu, Yan Tong, Wu Zhu, Zheng Meimei, Zhu Feng, Zhu Hui
State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China.
Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Front Cell Dev Biol. 2022 Apr 25;10:757042. doi: 10.3389/fcell.2022.757042. eCollection 2022.
Serine proteases are involved in many physiological activities as initiators of proteolytic cascades, and some members have been reported to play roles in male reproduction. Transmembrane serine protease 12 (TMPRSS12) has been shown to regulate sperm motility and uterotubal junction migration in mice, but its role in the testis remains unknown. In this study, we verified that TMPRSS12 was expressed in the spermatocytes and spermatids of testis and the acrosome of sperm. Mice deficient in exhibited male sterility. In meiosis, TMPRSS12 was demonstrated to regulate synapsis and double-strand break repair; spermatocytes of mice underwent impaired meiosis and subsequent apoptosis, resulting in reduced sperm counts. During spermiogenesis, TMPRSS12 was found to function in the development of mitochondria; abnormal mitochondrial structure in sperm led to reduced availability of ATP, impacting sperm motility. The differential protein expression profiles of testes in and wild-type mice and further molecule identification revealed potential targets of TMPRSS12 related to meiosis and mitochondrial function. Besides, TMPRSS12 was also found to be involved in a series of sperm functions, including capacitation, acrosome reaction and sperm-egg interaction. These data imply that TMPRSS12 plays a role in multiple aspects of male reproduction.
丝氨酸蛋白酶作为蛋白水解级联反应的启动因子参与许多生理活动，并且已有报道称一些成员在雄性生殖中发挥作用。跨膜丝氨酸蛋白酶12（TMPRSS12）已被证明可调节小鼠的精子活力和输卵管-子宫结合部迁移，但其在睾丸中的作用仍不清楚。在本研究中，我们证实TMPRSS12在睾丸的精母细胞和精子细胞以及精子的顶体中表达。缺乏TMPRSS12的小鼠表现出雄性不育。在减数分裂过程中，TMPRSS12被证明可调节联会和双链断裂修复；TMPRSS12基因敲除小鼠的精母细胞减数分裂受损并随后发生凋亡，导致精子数量减少。在精子发生过程中，发现TMPRSS12在线粒体发育中发挥作用；TMPRSS12基因敲除小鼠精子的线粒体结构异常导致ATP可用性降低，影响精子活力。TMPRSS12基因敲除小鼠和野生型小鼠睾丸的差异蛋白质表达谱以及进一步的分子鉴定揭示了与减数分裂和线粒体功能相关的TMPRSS12潜在靶点。此外，还发现TMPRSS12参与一系列精子功能，包括获能、顶体反应和精卵相互作用。这些数据表明TMPRSS12在雄性生殖的多个方面发挥作用。
