Melatonin prevents oocyte aging in the mouse and extends the window for optimal fertilization <em>in vitro</em> — ASN Events

Melatonin prevents oocyte aging in the mouse and extends the window for optimal fertilization in vitro (#50)

Tessa Lord 1 , R. John Aitken 1
  1. University of Newcastle, Callaghan, NSW, Australia

It is well known that oocyte quality has a prominent effect on fertilization success and developmental potential of resulting embryos. Unfortunately, oocyte quality rapidly deteriorates with time following ovulation via a degenerative process known as oocyte ‘aging’. Oocyte aging is associated not only with a decreased receptivity for fertilization, but also with an elevated risk for the production of embryos and offspring with abnormal or retarded development. Oocyte aging is of particular concern in assisted reproduction settings, where up to 40% of oocytes fail to fertilize during IVF and are thereby subjected to ‘next-day’ rescue ICSI; despite the fact that these oocytes have most likely deteriorated in quality.

Recent research in our laboratory has identified oxidative stress as a primary contributor to the aging process of the mouse oocyte in vitro, with a significant time-dependent increase in levels of reactive oxygen species (ROS) being detected (P<0.001) in aged oocytes. This elevation in oxidative stress coincides with the appearance of known characteristics of oocyte aging such as spontaneous activation, as well as with markers for apoptosis such as caspase induction and phosphatidylserine externalisation. Importantly, our research has demonstrated that following supplementation of oocyte culture medium with the antioxidant melatonin, not only are the aforementioned signs of aging attenuated, but the window for optimal fertilization of these oocytes is significantly increased (P<0.05). Oocytes ‘aged’ in the presence of melatonin for 8 and 16 h in vitro were also more likely to reach the blastocyst stage (P<0.05), and these blastocysts exhibited decreased levels of apoptosis when compared to control ‘aged’ embryos (P<0.05). These data indicate that by using melatonin to control oxidative stress within the post-ovulatory period, we may be able to safely delay the oocyte ‘aging’ process in vitro, thereby increasing the window for optimal fertilization and potentially reducing the likelihood of abnormalities in the offspring when delayed fertilization is unavoidable.