

A good quality egg at the right time (#1)

Rebecca Robker 1
  1. University of Adelaide, Adelaide, SA, Australia

The ovary consists of highly specialised cell types, which produce a microenvironment for the oocyte that establishes its developmental potential, i.e. its ability to make an embryo. Ovulation- the timely release of a good quality, developmentally competent oocyte from the ovary is tightly regulated by hormones and environmental conditions to precisely synchronise reproductive events for fertilisation and the generation of new life. Poor oocyte quality however leads to impaired blastocyst formation and a legacy of poor fetal growth and ill health. Remarkably, the normal cellular mechanisms controlling these physiological processes fundamental for reproduction and offspring health are poorly defined. Our research aims to identify cellular pathways in the ovary that regulate oocyte quality and ovulation, particularly those incorporating maternal hormone, immunological and metabolic inputs.

We have contributed key discoveries in dissecting the cellular mechanisms by which the oocyte is released from the ovary into the oviduct for fertilisation; specifically, that cell cycle regulator cyclin D2 and the progesterone receptor transcription factor are essential for ovulation. Using null mouse models and microarray analyses we have identified downstream gene products that mediate the dynamic tissue remodelling processes that facilitate the release of the oocyte. Using mice lacking specific immune cell receptors, we have also identified cellular mechanisms by which immune cells directly influence remodelling events in the ovary; for instance ICAM-1 (an adhesion receptor that tethers leukocytes for migration into tissues) is involved in ovulation and luteal regression. Clinically, we are investigating why obesity impairs female fertility. We have shown that obesity in female mice decreases oocyte mitochondrial activity and alters subsequent fetal development. This effect is associated with alterations in the follicular microenvironment, particularly lipid metabolism and endoplasmic reticulum stress pathways. We have recently identified interventions that can normalise these cellular defects and improve embryo outcomes.