Department of Veterinary and Animal Sciences, University of Massachusetts-Amherst, Integrated Sciences Building 427S, 661 North Pleasant Street, Amherst MA 01003, USA.
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, MA, USA.
Biol Reprod. 2020 Aug 4;103(2):264-274. doi: 10.1093/biolre/ioaa064.
Male contraception is a very active area of research. Several hormonal agents have entered clinical trials, while potential non-hormonal targets have been brought to light more recently and are at earlier stages of development. The general strategy is to target genes along the molecular pathways of sperm production, maturation, or function, and it is predicted that these novel approaches will hopefully lead to more selective male contraceptive compounds with a decreased side effect burden. Protein kinases are known to play a major role in signaling events associated with sperm differentiation and function. In this review, we focus our analysis on the testis-specific serine kinase (TSSK) protein family. We have previously shown that members of the family of TSSKs are postmeiotically expressed in male germ cells and in mature mammalian sperm. The restricted postmeiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggests that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the Tssk6 knockout (KO) mice and of the double Tssk1 and Tssk2 KO mice and by the male subfertile phenotype observed in a Tssk4 KO mouse model.
男性避孕是一个非常活跃的研究领域。几种激素制剂已经进入临床试验，而最近则发现了潜在的非激素靶点，处于开发的早期阶段。一般的策略是针对精子发生、成熟或功能的分子途径中的基因，预计这些新方法将有望带来更具选择性的男性避孕药，副作用负担更小。蛋白激酶在与精子分化和功能相关的信号事件中起着重要作用。在这篇综述中，我们将分析重点放在睾丸特异性丝氨酸激酶（TSSK）蛋白家族上。我们之前已经表明，TSSK 家族的成员在后减数分裂期在雄性生殖细胞和成熟的哺乳动物精子中表达。TSSK 的减数分裂后表达受限以及磷酸化在信号转导过程中的重要性强烈表明，TSSK 在生殖细胞分化和/或精子功能中具有重要作用。这一预测得到了 Tssk6 敲除（KO）小鼠和 Tssk1 和 Tssk2 KO 双敲除小鼠的不育表型以及 Tssk4 KO 小鼠模型中观察到的男性生育力低下表型的支持。
