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,
Marcos Morgan,
Francesco DeMayo
Affiliations
Ru-pin Alicia Chi
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Xiaojiang Xu
Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Jian-Liang Li
Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Xin Xu
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Guang Hu
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Paula Brown
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Cynthia Willson
Integrated Laboratory Systems LLC, Research Triangle Park, NC 27709, USA
Oleksandr Kirsanov
Department of Anatomy & Cell Biology at the Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA
Christopher Geyer
Department of Anatomy & Cell Biology at the Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA; East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA
Chou-Long Huang
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa, IA 52242, USA
Marcos Morgan
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
Francesco DeMayo
Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, Durham, NC 27709, USA; Corresponding author
Summary: 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.
