@article{a1d46a08f2944ab68eba83344786d7ac,
title = "WNK1 is required during male pachynema to sustain fertility",
abstract = "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 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 regulates MTOR activity and impact translation on a broader spectrum.",
keywords = "Cell biology, Molecular biology, Omics, Physiology, Transcriptomics",
author = "Chi, {Ru pin Alicia} and Xiaojiang Xu and Li, {Jian Liang} and Xin Xu and Guang Hu and Paula Brown and Cynthia Willson and Oleksandr Kirsanov and Christopher Geyer and Huang, {Chou Long} and Marcos Morgan and Francesco DeMayo",
note = "Funding Information: The authors thank Zhao Fei for initial guidance and Marine Baptissart for assisting with the gene ontology analysis and sharing the ribosome illustration for the graphical abstract. We thank Sylvia Hewitt, Humphrey Yao, and Manas Ray for reviewing the manuscript. We appreciate support from the NIEHS animal facility, the Knockout Mouse Core, the Digital Imaging Core, the Bioinformatics Support Group, the Epigenomics and DNA Sequencing Core and the Fluorescent Microscopy and Imaging Core of NIEHS for their support and guidance with specialized techniques. Finally, we used illustrations (“Intracellular components”) from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/) for the graphical abstract. This study was supported by the NIH grant ZIAES103311 to FJD, ZIAES103339 to MM, and R01 DK111542 to CLH. Conceptualization: R.A.C. F.D. Methodology: R.A.C. X.X. Xin.Xu. G.H. P.B. O.K. C.G., Investigation: R.A.C. X.X. C.W. Visualization: R.A.C. J.L. G.H. C.G. M.M. Supervision: R.A.C. J.L. M.M. F.D. Writing—original draft: R.A.C. Writing—review & editing: R.A.C. C.G. M.M. F.D. The authors declare no competing interests. Funding Information: The authors thank Zhao Fei for initial guidance and Marine Baptissart for assisting with the gene ontology analysis and sharing the ribosome illustration for the graphical abstract. We thank Sylvia Hewitt, Humphrey Yao, and Manas Ray for reviewing the manuscript. We appreciate support from the NIEHS animal facility, the Knockout Mouse Core, the Digital Imaging Core, the Bioinformatics Support Group, the Epigenomics and DNA Sequencing Core and the Fluorescent Microscopy and Imaging Core of NIEHS for their support and guidance with specialized techniques. Finally, we used illustrations (“Intracellular components”) from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License ( https://creativecommons.org/licenses/by/3.0/ ) for the graphical abstract. This study was supported by the NIH grant ZIAES103311 to FJD, ZIAES103339 to MM, and R01 DK111542 to CLH. Publisher Copyright: {\textcopyright} 2023",
year = "2023",
month = sep,
day = "15",
doi = "10.1016/j.isci.2023.107616",
language = "English (US)",
volume = "26",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "9",
}