Searchable abstracts of presentations at key conferences on reproductive biology and medicine
Reproduction Abstracts (2016) 3 O004 | DOI: 10.1530/repabs.3.O004

Oral Communications 1: Ovary

Oocyte maturation arrest in endometriosis is caused by elevated levels of Reactive Oxygen Species and enforced via a DNA Damage Response and the Spindle Assembly Checkpoint pathway

Mukhri Hamdan2, Keith Jones1, Ying Cheong2 & Simon Lane1

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1University of Southampton, Southampton, UK; 2Complete Fertility Centre, Southampton, UK.


Introduction: It has recently been demonstrated that mouse oocytes respond to DNA damage by arresting in Meiosis I. This arrest has been shown to require the activity of the Spindle Assembly Checkpoint (SAC) and the DNA Damage Response (DDR). Given oocytes lack the equivalent of a G2/M checkpoint for DNA damage, the SAC response may be critical to defend against formation of DNA damaged embryos. It is currently unknown whether the DDR SAC pathway is sensitive to physiological or even pathological levels of DNA damage. We investigate the effect of endometriosis, a disease affecting ~10% of women of reproductive age, and associated with elevated Reactive Oxygen Species (ROS) and reduced fertility, on oocyte maturation.

Methods: Here we expose mouse oocytes to follicular fluid (FF) from patients with or without endometriosis and assess their ability to complete maturation. We measure ROS and DNA damage in the oocytes and use kinase inhibitors and antisense knockdown to elucidate the pathways involved.

Results & Discussion: We found that FF from patients with endometriosis, but not control FF, elevated ROS and DNA damage in the oocyte, which led to a SAC mediated metaphase I arrest. FF from patients with endometriosis activated ATM kinase, indicating the involvement of the DNA Damage Response. Oocyte maturation could be rescued by blocking ROS, suggesting this is the primary trigger for arrest. We demonstrate for the first time that meaningful levels of ROS and DNA damage can trigger DDR-SAC arrest in oocytes and also provide explanation for the subfertility associated with endometriosis. Furthermore, the pathway proposed provides pharmacological targets and could inform future clinical practice.

Volume 3

Society for Reproduction and Fertility Annual Conference 2016

Winchester, UK
11 Jul 2016 - 11 Jul 2016

Society for Reproduction and Fertility 

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