The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Connecting the fetal and genetic origins of PCOS (#321)

Monica D Hartanti 1 , Katja Hummitzsch 1 , Helen Irving-Rodgers 2 , Ray Rodgers 1
  1. Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA, Australia
  2. School of Medicine Science, Griffith University, Gold Coast Campus, Gold Coast, Queensland, Australia

Polycystic Ovary Syndrome (PCOS) is a multifactorial reproductive and metabolic endocrine disorder with increased ovarian stroma. It is believed that PCOS has genetic and fetal origins. Recent genotyping studies have discovered susceptibility loci containing candidate genes for PCOS [1]. However, little is known about expression patterns and interactions during fetal ovarian development. This study investigated the expression of these 19 candidate genes and additional (AMH, AR, TGFB1I1) genes throughout gestation. Ovaries of bovine fetuses across gestation (n=27) and adults (n=5) were collected for gene expression analyses. Except DENND1A.V2 and SUMO1P1, all genes were expressed in fetal and adult ovaries. During ovarian development, the expression of GATA4, HMGA2, TOX3, DENND1A1.V1 and FBN3 was initially high and decreased at about the end of the first trimester, whilst FSHR, AMH, INSR, AR and TGFB1I1 increased from around the second trimester. Those genes were strongly correlated with gestational age. LHCGR expression was high in the first trimester, decreased to its lowest by 130 days of gestation, and then sharply increased until the end of gestation. The expression of the remaining genes was not correlated with gestational age. In the adult, most genes were expressed significantly lower compared to fetal developmental stages (p<0.05), except LHCGR, FSHB and ERBB4. FBN3, HMGA2 and TOX3 expression decreased significantly during follicle formation in the fetal ovary and were lowest in the adult ovary (p<0.05), whereas AMH and FSHR were expressed highly in the adult compared to the fetal ovary (p<0.05). Collectively, GATA4, HMGA2, TOX3, LHCGR (before 150 days) and FBN3 were highly expressed  and positively correlated with each other during early development when stroma first develops, while FSHR, AMH, INSR, AR and TGFB1I1 were expressed during folliculogenesis and negatively correlated with the early expressed genes. Dysregulation of these genes during gestation might cause the PCOS phenotype later in life.

  1. [1] Jones MR, Goodarzi MO. Genetic determinants of polycystic ovary syndrome: Progress and future directions. Fertil Steril 2016;106: 25-32.