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WNK1 is required during male pachynema to sustain fertility
Journal article   Open access   Peer reviewed

WNK1 is required during male pachynema to sustain fertility

Ru-pin Alicia Chi, Xiaojiang Xu, Jian-Liang Li, Xin Xu, Guang Hu, Paula Brown, Cynthia Willson, Oleksandr Kirsanov, Christopher Geyer, Chou-Long Huang, …
iScience, Vol.26(9), 107616
09/15/2023
DOI: 10.1016/j.isci.2023.107616
PMCID: PMC10485039
PMID: 37694147
url
https://doi.org/10.1016/j.isci.2023.107616View
Published (Version of record) Open Access

Abstract

WNK1 is an important regulator in many physiological functions and 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 Wnk1 in mid-pachytene spermatocytes using the Wnt7a-Cre 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 Wnk1-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 Wnk1 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 regulate MTOR activity and impact translation on a broader spectrum.

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