ESA-SRB-AOTA 2019

Ageing modulates expression of oocyte DNA repair genes during the germinal vesicle-metaphase II transition in mice after ovulation induction (#41)

Fabrizzio Horta 1 , Aravind Ravichandran 1 , Sally Catt 1 , Beverley Vollenhoven 1 , Peter Temple-Smith 1
  1. EPRD, Obstetrics and Gynecology, Monash University, Melbourne, VIC, Australia

Oocyte quality and reproductive outcome are affected by advanced maternal age, ovarian stimulation and method of oocyte maturation in human assisted reproduction. Understanding molecular signatures of the oocyte DNA repair capacity can assist in identifying the mechanisms leading to poor oocyte quality in ageing. The aim of this study was to compare the effects of ageing, method of oocyte maturation (in vivo/in vitro) and ovarian stimulation conditions on the relative expression of DNA repair genes in germinal vesicle (GV) and metaphase II (MII) oocytes. The relative expression of ninety DNA repair genes was compared in GV and in vitro matured (IVM) MII oocytes from unstimulated and hormone-stimulated (PMSG or anti-inhibin serum [AIS] with an hCG trigger) young (5-8 weeks) and old (42-45 weeks) C57BL6 mice using the Taqman assay.  A general pattern of significant down-regulation in DNA repair genes was observed in MIIs compared to GVs from the young mice, irrespective of the method used to produce mature oocytes.  The number of significantly down-regulated genes in IVM-MIIs from younger females, were greater than in vivo-MII (Young IVM-MII: 38 genes; Young in vivo-MII: 25 genes, 95%-IC). In aged oocytes, the expression pattern was reversed, with more DNA repair genes significantly up-regulated in IVM-MII and in vivo-MII oocytes than GVs (Old IVM-MII: 22 genes; Old in vivo-MII: 12 genes, 95%-IC). Also, in older females more DNA repair genes were down-regulated in IVM-MII oocytes than in in-vivo-MIIs (Old IVM-MII: 13 genes; Old in-vivo-MII: 4 genes, 95%-IC), suggesting that IVM has a different effect on MII repair genes than in vivo maturation in stimulated oocytes, with potential repercussions on oocyte quality. The key DNA damage response gene, H2AFX, was always down-regulated in MII oocytes compared to GV oocytes irrespective of maturation type (95%-IC). Ageing modulates DNA repair gene expression during the GV-MII transition.