Melatonin protects against maternal obesity‐associated oxidative stress and meiotic defects in oocytes via the <scp>SIRT</scp>3‐<scp>SOD</scp>2‐dependent pathway

<jats:title>Abstract</jats:title><jats:p>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 (<jats:styled-content style="fixed-case">HFD</jats:styled-content>) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (<jats:styled-content style="fixed-case">ROS</jats:styled-content>) levels in oocytes from obese mice. Oral administration of melatonin to <jats:styled-content style="fixed-case">HFD</jats:styled-content> mice not only reduces <jats:styled-content style="fixed-case">ROS</jats:styled-content> 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 <jats:styled-content style="fixed-case">HFD</jats:styled-content> 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 <jats:styled-content style="fixed-case">SIRT</jats:styled-content>3‐<jats:styled-content style="fixed-case">SOD</jats:styled-content>2‐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.</jats:p>