Melatonin ameliorates the advanced maternal age-associated meiotic defects in oocytes through the SIRT2-dependent H4K16 deacetylation pathway

Abstract

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 SIRT2depenendet H4K16 deacetylation pathway.

Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro

“…One of the most effective means is maintain the balance of intracellular redox state in aged oocytes through exogenous supplementation of antioxidant compounds. The typical antioxidants such as melatonin 10 – 12 , resveratrol 13 – 15 , N‐acetyl‐L‐cysteine 16 , Coenzyme Q10 17 , etc., have been proved to improve the aged oocyte quality.…”

Influence of Maternal Age and Gestational Age on Breast Milk Antioxidants During the First Month of Lactation

“…Regarding the influence of maternal age on antioxidants, we found that only melatonin levels were significantly affected during the first month of breastfeeding, also confirmed by the linear model. Maternal age is one of the main factors limiting antioxidant production in humans, as established by previous studies, and extensively demonstrated for melatonin [49,50]. Melatonin levels in plasma are known to decline with age [51] and plasma concentrations match those found in BM [38].…”

Applications of Melatonin in Female Reproduction in the Context of Oxidative Stress

“…SIRT2 is a key effector of oocyte meiosis, and SIRT2-controlled histone H4K16 deacetylation is essential for oocyte meiosis. Li et al revealed that melatonin could improve oocyte quality in aged mice through the SIRT2-dependent H4K16 deacetylation pathway [ 28 ]. Also, melatonin could counteract mitochondrial oxidative damage via SIRT3/FOXO3a pathway.…”