Open AccessMelatonin ameliorates the advanced maternal age-associated meiotic defects in oocytes through the SIRT2-dependent H4K16 deacetylation pathway
Author(s) -
Congyang Li,
Xi He,
Zhipeng Huang,
Longsen Han,
Xinghan Wu,
Ling Li,
Yongan Xin,
Jun Ge,
Jiahao Sha,
Zhiqiang Yin,
Qiang Wang
Publication year - 2020
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.102703
Subject(s) - sirt2 , melatonin , oocyte , meiosis , acetylation , sirt6 , histone h4 , histone , microbiology and biotechnology , biology , epigenetics , genetics , sirtuin , endocrinology , gene , embryo
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.