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Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception†.
Biology of Reproduction ( IF 3.6 ) Pub Date : 2020-04-27 , DOI: 10.1093/biolre/ioaa064
Ana M Salicioni 1, 2 , María G Gervasi 1 , Julian Sosnik 3 , Darya A Tourzani 1, 4 , Saman Nayyab 1, 2 , Diego A Caraballo 5 , Pablo E Visconti 1, 2
Affiliation  

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.

中文翻译:

男性生育力中睾丸特异性丝氨酸激酶蛋白家族并作为非激素男性避孕的靶点†。

男性避孕是一个非常活跃的研究领域。几种激素药物已进入临床试验,而潜在的非激素靶标最近才被发现并处于早期开发阶段。一般策略是沿着精子产生、成熟或功能的分子途径靶向基因,预计这些新方法将有望导致具有更低副作用负担的更具选择性的男性避孕化合物。已知蛋白激酶在与精子分化和功能相关的信号事件中起主要作用。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 家族的成员在雄性生殖细胞和成熟的哺乳动物精子中进行减数分裂后表达。TSSKs 的减数分裂后表达受限以及磷酸化在信号传导过程中的重要性强烈表明 TSSKs 在生殖细胞分化和/或精子功能中具有重要作用。该预测得到了报道的不育表型的支持Tssk6敲除 (KO) 小鼠和双Tssk1Tssk2 KO 小鼠以及在Tssk4 KO 小鼠模型中观察到的雄性低生育力表型。
更新日期:2020-04-27
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