Melatonin protects against maternal obesity-associated oxidative stress and meiotic defects in oocytes via the SIRT3-SOD2-dependent pathway.

Abstract

Maternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high-fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice. Oral administration of melatonin to HFD mice not only reduces ROS generation, but also prevents spindle/chromosome anomalies in oocytes, consequently promoting the developmental potential of early embryos. Consistent with this finding, we find that melatonin supplement during in vitro maturation also markedly attenuates oxidative stress and meiotic defects in HFD oocytes. Finally, by performing morpholino knockdown and acetylation-mimetic mutant overexpression assays, we reveal that melatonin ameliorates maternal obesity-induced defective phenotypes in oocytes through the SIRT3-SOD2-dependent mechanism. In sum, our data uncover the marked beneficial effects of melatonin on oocyte quality from obese females; this opens a new area for optimizing culture system as well as fertility management.

• Authors: Longsen Han, Haichao Wang, Ling Li, Xiaoyan Li, Juan Ge, Russel J Reiter, Qiang Wang
• Journal: Journal of pineal research (J Pineal Res) Vol. 63 Issue 3 (Oct 2017) ISSN: 1600-079X [Electronic] England
• PMID: 28658527 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antioxidants
• Reactive Oxygen Species
• Sirt3 protein, mouse
• Superoxide Dismutase
• superoxide dismutase 2
• Sirtuin 3
• Melatonin

Topics

• Acetylation (drug effects)
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Diet, High-Fat
• Drug Evaluation, Preclinical
• Embryonic Development (drug effects)
• Female
• Meiosis (drug effects)
• Melatonin (pharmacology, therapeutic use)
• Mice, Inbred ICR
• Obesity (complications)
• Oocytes (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Pregnancy
• Pregnancy Complications (etiology, prevention & control)
• Reactive Oxygen Species (metabolism)
• Sirtuin 3 (metabolism)
• Superoxide Dismutase (metabolism)