Research Paper Volume 12, Issue 2 pp 1610—1623
Melatonin ameliorates the advanced maternal age-associated meiotic defects in oocytes through the SIRT2-dependent H4K16 deacetylation pathway
- 1 State Key Laboratory of Reproductive Medicine, Suzhou Municipal Hospital, Department of Histology and Embryology, Nanjing Medical University, Nanjing, China
- 2 Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
- 3 Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
received: November 19, 2019 ; accepted: December 27, 2019 ; published: January 24, 2020 ;https://doi.org/10.18632/aging.102703
How to Cite
Copyright © 2020 Li 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.
It has been widely reported that advanced maternal age impairs oocyte quality. To date, various molecules have been discovered to be involved in this process. However, prevention of fertility issues associated with maternal age is still a challenge. In the present study, we find that both in vitro supplement and in vivo administration of melatonin are capable of alleviating the meiotic phenotypes of aged oocytes, specifically the spindle/chromosome disorganization and aneuploidy generation. Furthermore, we identify SIRT2 as a critical effector mediating the effects of melatonin on meiotic structure in old oocytes. Candidate screening shows that SIRT2-controlled deacetylation of histone H4K16 is essential for maintaining the meiotic apparatus in oocytes. Importantly, non-acetylatable-mimetic mutant H4K16R partially rescues the meiotic deficits in oocytes from reproductive aged mice. In contrast, overexpression of acetylation-mimetic mutant H4K16Q abolishes the beneficial effects of melatonin on the meiotic phenotypes in aged oocytes. To sum up, our data uncover that melatonin alleviates advanced maternal aged-associated meiotic defects in oocytes through the SIRT2-depenendet H4K16 deacetylation pathway.