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

J Pineal Res. 2017 Oct;63(3). doi: 10.1111/jpi.12431. Epub 2017 Jul 18.

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.

Keywords: meiosis; melatonin; obesity; oocyte quality; oxidative stress.

MeSH terms

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

Substances

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