Uncover fetal and genetic origins of PCOS
Monica D Hartanti(a*,b). Katja Hummitzsch(b). Helen F Irving-Rodgers (b,c). Raymond J Rodgers (b).
a) Department of Medical Biology, Faculty of Medicine, Trisakti University
Jl Kyai Tapa No.260, Jakarta, Indonesia
*mdhartanti[at]trisakti.ac.id
b) Discipline of Obstetrics and Gynaecology, Robinson Research Institute, School of Medicine, University of Adelaide
Adelaide, South Australia 5005
c) School of Medicine Science, Griffith University
Gold Coast Campus, Queensland, Australia 4215
Abstract
During fetal ovarian development, the stroma penetrates and expands in the developing ovary and might play a role in the formation of ovigerous cords, follicles, and the ovarian surface epithelium. Pertubation of stromal development might lead to some reproductive diseases such as Polycystic Ovary Syndrome (PCOS). PCOS is a multifactorial reproductive and metabolic endocrine disorder with increased ovarian stroma. Recent genotyping studies have discovered susceptibility loci containing candidate genes for PCOS. However, little is known about their expression patterns and interactions during ovarian development. Using bovine ovaries (n=27) due to their histological similarity to human ovaries, we investigated stromal behaviour morphometrically in the ovarian cortex and the expression of these candidate genes throughout gestation. The stromal proportion and stromal total volume in the cortex significantly increased (P < 0.05) throughout gestation. Except SUMO1P1, all candidate genes were expressed in fetal ovaries. The expression of GATA4, HMGA2, TOX3, DENND1A1 and FBN3 was initially high and decreased at about the end of the first trimester, whilst FSHR and INSR, 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. FBN3, HMGA2 and TOX3 expression decreased significantly during follicle formation in the fetal ovary. Collectively, GATA4, HMGA2, TOX3, LHCGR (before 150 days) and FBN3 were abundantly expressed and positively correlated with each other during early development when the cortical stromal expansion peaked, 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.
Keywords: Fetal, ovary, stroma, PCOS
Topic: Adolescent and reproductive health