Oral Presentation Australian Society for Medical Research Annual Scientific Meeting 2016

Age-related female infertility: The need for early diagnosis and public education (#31)

Jessie M Sutherland 1 2
  1. School of Biomedical Science & Pharmacy, University Of Newcastle, Callaghan, NSW, Australia
  2. Pregnancy & Reproduction Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia

Due to worldwide declining reproductive health, human infertility is a now major clinical problem, with 1 in 6 couples currently affected. Within Australia, the failure to conceive has led to unprecedented rates of assisted conception, with over 65,000 IVF cycles performed in 2013 costing > $500 million. Unfortunately, the success rates of current treatments resulting in a live birth are less than 20%. And as women age these rates plummet further, due largely to the age-related decline in the quality and quantity of their eggs (oocytes).

Age-related female infertility is caused by the steady loss of non-growing oocytes (primordial follicles) from the ovaries through activation of growth and subsequent ovulation or apoptosis. This process begins in utero in humans, with its adverse effects on fertility observed over 13 years prior to menopause. My research focuses on uncovering and understanding the crucial role of early ovary development in determining a woman’s future fertility.

Our group has previously demonstrated that the JAK/STAT signalling pathway serves an essential role in controlling primordial follicle activation1. In this study we went on to characterise pivotal members of this pathway and establish their involvement in the regulation of the ovary and thus female fertility.

JAK1 was identified as a critical upstream regulator of primordial follicle activation. Whole ovary explant in vitro culture studies demonstrated that chemical inhibition of JAK1 activity during early postnatal development in mice caused accelerated follicle activation and increased apoptosis. Furthermore, in our transgenic mouse model of early onset menopause, we observed the differential expression of important JAK/STAT members. These findings provide the molecular knowledge inherent for the development of urgently needed diagnostics and treatments for female infertility.

  1. Sutherland, J.M., et al., Suppressor of cytokine signaling 4 (SOCS4): moderator of ovarian primordial follicle activation. J Cell Physiol, 2012. 227(3): p. 1188-98.