Chi Ru-Pin Alicia, Xu Xiaojiang, Li Jian-Liang, Xu Xin, Hu Guang, Brown Paula, Willson Cynthia, Kirsanov Oleksandr, Geyer Christopher, Huang Chou-Long, Morgan Marcos, DeMayo Francesco
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, NC 27709, USA.
iScience. 2023 Aug 12;26(9):107616. doi: 10.1016/j.isci.2023.107616. eCollection 2023 Sep 15.
WNK1 is an important regulator in many physiological functions, yet its role in male reproduction is unexplored. In the male germline, WNK1 is upregulated in preleptotene spermatocytes indicating possible function(s) in spermatogenic meiosis. Indeed, deletion of in mid-pachytene spermatocytes using the mouse led to male sterility which resembled non-obstructive azoospermia in humans, where germ cells failed to complete spermatogenesis and produced no sperm. Mechanistically, we found elevated MTOR expression and signaling in the -depleted spermatocytes. As MTOR is a central mediator of translation, we speculated that translation may be accelerated in these spermatocytes. Supporting this, we found the acrosome protein, ACRBP to be prematurely expressed in the spermatocytes with deletion. Our study uncovered an MTOR-regulating factor in the male germline with potential implications in translation, and future studies will aim to understand how WNK1 regulates MTOR activity and impact translation on a broader spectrum.
WNK1是多种生理功能中的重要调节因子，但其在雄性生殖中的作用尚未得到探索。在雄性生殖细胞中，WNK1在前细线期精母细胞中上调，表明其在生精减数分裂中可能具有功能。事实上，使用特定小鼠模型在粗线期中期精母细胞中敲除WNK1会导致雄性不育，类似于人类的非梗阻性无精子症，即生殖细胞无法完成精子发生且不产生精子。从机制上讲，我们发现在WNK1缺失的精母细胞中MTOR表达和信号传导升高。由于MTOR是翻译的核心调节因子，我们推测这些精母细胞中的翻译可能会加速。支持这一观点的是，我们发现顶体蛋白ACRBP在WNK1缺失的精母细胞中过早表达。我们的研究在雄性生殖细胞中发现了一个MTOR调节因子，其对翻译具有潜在影响，未来的研究旨在了解WNK1如何调节MTOR活性以及在更广泛范围内对翻译的影响。
