Mechanistic target of rapamycin kinase (<i>Mtor</i>) is required for spermatogonial proliferation and differentiation in mice.

Jun Cao; Zuo-bao Lin; Ming-han Tong; Yong-lian Zhang; Yi-ping LI; Yu-chuan Zhou

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Mechanistic target of rapamycin kinase (Mtor) is required for spermatogonial proliferation and differentiation in mice.

Author: Jun CAO ¹ ; Zuo-Bao LIN ² ; Ming-Han TONG ¹ ; Yong-Lian ZHANG ¹ ; Yi-Ping LI ² ; Yu-Chuan ZHOU ¹
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1. State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
2. State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: Mtor; male fertility; mice; spermatogenesis; spermatogonia; testis
MeSH: Animals; Cell Proliferation/genetics*; Fertility/genetics*; Male; Mice; Mice, Knockout; Spermatogenesis/genetics*; Spermatogonia/metabolism*; TOR Serine-Threonine Kinases/metabolism*; Testis/metabolism*
From: Asian Journal of Andrology 2020;22(2):169-176
CountryChina
Language:English
Abstract: Spermatogonial development is a vital prerequisite for spermatogenesis and male fertility. However, the exact mechanisms underlying the behavior of spermatogonia, including spermatogonial stem cell (SSC) self-renewal and spermatogonial proliferation and differentiation, are not fully understood. Recent studies demonstrated that the mTOR complex 1 (mTORC1) signaling pathway plays a crucial role in spermatogonial development, but whether MTOR itself was also involved in any specific process of spermatogonial development remained undetermined. In this study, we specifically deleted Mtor in male germ cells of mice using Stra8-Cre and assessed its effect on the function of spermatogonia. The Mtor knockout (KO) mice exhibited an age-dependent perturbation of testicular development and progressively lost germ cells and fertility with age. These age-related phenotypes were likely caused by a delayed initiation of Mtor deletion driven by Stra8-Cre. Further examination revealed a reduction of differentiating spermatogonia in Mtor KO mice, suggesting that spermatogonial differentiation was inhibited. Spermatogonial proliferation was also impaired in Mtor KO mice, leading to a diminished spermatogonial pool and total germ cell population. Our results show that MTOR plays a pivotal role in male fertility and is required for spermatogonial proliferation and differentiation.