Research Paper Volume 12, Issue 17 pp 17099—17113
Sirt6 is required for spermatogenesis in mice
- 1 State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
- 2 University of the Chinese Academy of Sciences, Beijing 100049, China
- 3 Department of Urology, Peking University Third Hospital, Beijing 100191, China
- 4 Department of Andrology, Peking University Third Hospital, Beijing 100191, China
- 5 Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing 100191, China
- 6 Department of Human Sperm Bank, Peking University Third Hospital, Beijing 100191, China
Received: January 14, 2020 Accepted: June 19, 2020 Published: September 11, 2020
https://doi.org/10.18632/aging.103641How to Cite
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.