Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The role of JAK/STAT signalling in understanding premature ovarian failure (#443)

Jessie M Sutherland 1 2 , Emily R Frost 2 , Melissa Baldwin 2 , Kate A Redgrove 1 2 , Eileen A McLaughlin 2
  1. Hunter Medical Research Institute, Pregnancy and Reproduction Program, Newcastle, NSW, Australia
  2. Priority Research Centre for Reproductive Science, The University of Newcastle, Callaghan, NSW, Australia

Premature ovarian failure (POF) is a disease of infertility, diagnosed in 3% of all women, defined by the early onset of menopause before age 40. Although considered idiopathic, one of the primary causes of POF is the early loss of non-growing oocytes (primordial follicles) from the ovarian reserve due to their accelerated activation1. Unfortunately our poor understanding of the mechanism(s) controlling primordial follicle activation remains a major limitation in the treatment of women with POF.

We have previously established that the Janus kinase and Signal Transducer and Activator of Transcription and Suppressors of Cytokine Signalling (JAK/STAT/SOCS) pathways serves an essential role in controlling primordial follicle activation2. In this study we sought to characterise the pivotal members of this pathway and establish their role in the regulation of the ovarian reserve and thus female fertility.

Immunolocalisation and qPCR analysis across an ovarian developmental time-course in mice identified potential roles for JAK1, STAT3, SOCS2, SOCS4 and CISH in maintaining the primordial follicle reserve. While subcellular localisation of SOCS4 and CISH in pre- and post-ovulatory oocytes indicated unique and differential expression for these pathway suppressors during oogenesis. Whole ovary explant in vitro culture studies demonstrated that chemical inhibition of JAK1 activity during early postnatal development resulted in the accelerated activation of primordial follicles. Furthermore in two animal models of POF we have shown reduced expression of key JAK/STAT members.

These findings implicate the JAK/STAT/SOCS pathway as a potential target for the manipulation of the ovarian reserve. The knowledge gained in this study will assist in the development of urgently needed diagnostics and targeted therapeutic strategies towards the improved management and treatment of female infertility resulting from POF.

  1. De Vos M, Devroey P, and Fauser BC, Primary ovarian insufficiency. Lancet, 2010. 376(9744): p. 911-21.
  2. Sutherland JM, Keightley RA, Nixon B, Roman SD, Robker RL, Russell DL, McLaughlin EA. Suppressor of cytokine signaling 4 (SOCS4): Moderator of ovarian primordial follicle activation. Journal of Cellular Physiology, 2012. 227(3):1188-1198