Research Paper|Volume 12, Issue 17|pp 17099—17113

Sirt6 is required for spermatogenesis in mice

Huafang Wei^1,², Muhammad Babar Khawar^1,², Wenhao Tang³, Lina Wang^1,², Liying Wang^1,², Chao Liu^1,², Hui Jiang^3,^4,^5,⁶, Wei Li¹

¹State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
²University of the Chinese Academy of Sciences, Beijing 100049, China
³Department of Urology, Peking University Third Hospital, Beijing 100191, China
⁴Department of Andrology, Peking University Third Hospital, Beijing 100191, China
⁵Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing 100191, China
⁶Department of Human Sperm Bank, Peking University Third Hospital, Beijing 100191, China

Received: January 14, 2020Accepted: June 19, 2020Published: September 11, 2020

https://doi.org/10.18632/aging.103641

Copyright: © 2020 Wei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

SIRT6, a nuclear protein, has been implicated in a number of essential cellular processes, such as the DNA damage response, metabolic homeostasis, inflammation, tumorigenesis and aging. However, the role of Sirt6 in the regulation of spermatogenesis is yet unknown. In the present study, we successfully generated Sirt6^-/- mice on a C57BL6/ICR mixed background and found that some Sirt6^-/- mice survived beyond eight weeks. We further revealed that spermatogenesis in Sirt6^-/- mice was arrested at the elongated spermatid stage. Sirt6^-/- male mice were completely infertile and had an increased number of apoptotic spermatids. To our surprise, deacetylation activities of SIRT6 on H3K9ac, H3K18ac and H3K56c were not required for spermatogenesis. Therefore, our findings establish a novel link between Sirt6 and male fertility, suggesting an essential role of Sirt6 in spermatogenesis.