Ageing and ovarian stimulation modulate the relative levels of transcript abundance of oocyte DNA repair genes during the germinal vesicle-metaphase II transition in mice

• Published in: Journal of assisted reproduction and genetics 2021-01, Vol.38 (1), p.55-69
• Main Authors: Horta, Fabrizzio, Ravichandran, Aravind, Catt, Sally, Vollenhoven, Beverley, Temple-Smith, Peter
• Format: Article
• Language: English
• Subjects: Abundance; Aging; Aging - drug effects; Aging - genetics; Aging - pathology; Animals; Deoxyribonucleic acid; Developmental stages; DNA; DNA damage; DNA Damage - drug effects; DNA repair; DNA Repair - genetics; Female; Gene Expression Regulation, Developmental - drug effects; Gonadotropins; Gonadotropins, Equine - pharmacology; Gynecology; Histone H2A; Histones - genetics; Human Genetics; Humans; Inhibin; Inhibins - pharmacology; Medicine; Medicine & Public Health; Metaphase; Metaphase - genetics; Mice; Oocytes; Oocytes - drug effects; Oocytes - growth & development; Oocytes - metabolism; Oogenesis - drug effects; Ovaries; Ovulation Induction - methods; Pituitary (anterior); Pregnancy; Reproductive Medicine; Reproductive Physiology and Disease; Transcription
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-020-01981-6

Purpose Oocyte quality and reproductive outcome are negatively affected by advanced maternal age, ovarian stimulation and method of oocyte maturation during assisted reproduction; however, the mechanisms responsible for these associations are not fully understood. The aim of this study was to compare the effects of ageing, ovarian stimulation and in-vitro maturation on the relative levels of transcript abundance of genes associated with DNA repair during the transition of germinal vesicle (GV) to metaphase II (MII) stages of oocyte development. Methods The relative levels of transcript abundance of 90 DNA repair-associated genes was compared in GV-stage and MII-stage oocytes from unstimulated and hormone-stimulated ovaries from young (5–8-week-old) and old (42–45-week-old) C57BL6 mice. Ovarian stimulation was conducted using pregnant mare serum gonadotropin (PMSG) or anti-inhibin serum (AIS). DNA damage response was quantified by immunolabeling of the phosphorylated histone variant H2AX (γH2AX). Results The relative transcript abundance in DNA repair genes was significantly lower in MII oocytes compared to GV oocytes in young unstimulated and PMSG stimulated but was higher in AIS-stimulated mice. Interestingly, an increase in the relative level of transcript abundance of DNA repair genes was observed in MII oocytes from older mice in unstimulated, PMSG-stimulated and AIS-stimulated mice. Decreased γH2AX levels were found in both GV oocytes (82.9%) and MII oocytes (37.5%) during ageing in both ovarian stimulation types used (PMSG/AIS; p < 0.05). Conclusions In conclusion, DNA repair relative levels of transcript abundance are altered by maternal age and the method of ovarian stimulation during the GV-MII transition in oocytes.