Endocrine Abstracts (2017) 50 P355 | DOI: 10.1530/endoabs.50.P355

RNA-Sequencing reveals a downregulation of cholesterol metabolism pathways in granulosa cells from women with PCOS

A Lerner1, T Caraderi2, A Drong2, E Makrinou1, G Christopoulos3, M Liyanage4, S Lavery4, K Hardy1, C Lindgren2 & S Franks1

1Imperial College London, London, UK; 2University of Oxford, Oxford, UK; 3Imperial College NHS Trust, London, USA; 4Imperial College NHS Trust, London, UK.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with anovulatory infertility, menstrual disturbances and an adverse metabolic profile. Although the pathophysiology of PCOS remains unclear, dysregulation of gene expression has been previously shown in theca and granulosa cells. In this study, we used RNA-Sequencing to compare the transcriptomes of human granulosa cells from women with and without PCOS. Granulosa cells were retrieved during egg collection for in-vitro fertilisation from women with normal ovaries and regular cycles and women with polycystic ovaries and irregular cycles. RNA was extracted and processed for RNA-Sequencing. Quantitative PCR was used to validate changes in gene expression. RNA-Sequencing identified 21175 genes expressed in human granulosa cells. Of these, 450 genes were differentially expressed in women with PCOS (P<0.05, after controlling for multiple comparisons). Gene Ontology and Reactome pathway analysis highlighted a group of genes involved in cholesterol biosynthesis and metabolism that are highly enriched (19-fold increase, P<1.60E-16) in granulosa cells from women with PCOS. In total, a group of 21 cholesterol biosynthesis and metabolism genes were identified, and interestingly all showed reduced expression. These include downregulation of Hydroxy-3-methylglutaryl CoA synthases 1 and 2 (HMGCS1, 8-fold, P