Professor University of Adelaide Adelaide, South Australia, Australia
Abstract Authors: Raymond J. Rodgers1, Rafiatu Azumah1, Katja Hummitzsch1, Feng Tang1, Richard A. Anderson2
1Robinson Research Institute, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia
2Centre for Reproductive Health, Institute for Regeneration and Repair, University of Edinburgh, Edinburgh EH16 4UU, UK
Abstract Text: Studies of genetic controls of ovarian development in humans are limited due to ethical and supply issues. To advance our knowledge we have conducted analysis of RNA sequencing data from human fetal ovaries up until mid-gestation [4-18 weeks post coitum (wpc), n=18]. Data were obtained from Array Express (E-MTAB-6814) from the ‘Gene expression across mammalian organ development’ project. They were provided by the MRC-Wellcome Trust Human Developmental Biology Resource and were from elective abortions with normal karyotypes. Principal component analysis and heatmaps identified that the ovaries naturally clustered into three age groups; 4-6 wpc, 7-9 wpc and 10-18 wpc. Comparison of 7-9 wpc to 4-6 wpc, identified that WNT6, FYB2, DAZL, FOXL2, ESR1 and other genes were up-regulated whilst BMP5, FGF23, CDH9, ADAMTS18 and others were down-regulated. Transcriptional regulation networks associated with embryonic stem cells, human embryonic stem cell pluripotency and pathways involving cyclic AMP (cAMP) signalling were activated. These included cAMP signalling pathway itself, cAMP response element-binding protein (CREB) signalling pathway, G-protein coupled receptor signalling, eicosanoid signalling and dopamine-DARPP32 feedback in cAMP signalling. Comparison of 10-18 wpc with 7-9 wpc found that SPO11, DMRTC2, ZPBP2, PRDM9, SHCBP11, CLDN18 and others were up-regulated whilst HMGA2, ADGRF1, HBE1, HBZ, KCNJ1, TMPRSS2, FGF1, BMP5 and others were down-regulated. Retinoic acid receptor pathway was activated. However, most receptor stimulation involving cAMP signalling such as G-Protein coupled receptor signalling, GABA receptor signalling and IL-10 signalling were all inhibited. These studies in particular indicate an important role(s) for cAMP signalling in 7-9 wpc, a period of major transition from rapid germ and somatic cell proliferation to the onset of meiosis.
