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

Characterization of the granulosa-lutein cell transcriptome in women with Polycystic Ovary Syndrome (#85)

Avi Lerner 1 , M Coates 1 , T Caraderi 1 , A Markou 1 , L Owens 1 , C Simpson 1 , J Velupillai 1 , G Pool 1 , E Makrinou 1 , G Christopoulos 1 , S Lavery 1 , C L Bevan 1 , K Hardy 1 , C Lindgren 1 , S Franks 1
  1. Imperial College London, London, ENGLAND, United Kingdom

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with menstrual irregularities, anovulatory infertility and metabolic abnormalities. Although the aetiology and pathophysiology of PCOS remain unclear, granulosa cell dysfunction is a notable feature of the syndrome. In this study, we used a combination of RT-qPCR, RNA-Sequencing and pathway analysis to identify genes in granulosa cells that may be implicated in the pathogenesis of PCOS.


Granulosa-lutein cells were retrieved from women undergoing in-vitro fertilisation who had normal ovaries and regular cycles or polycystic ovaries and irregular cycles (anovPCOS) or polycystic ovaries with regular, ovulatory cycles (ovPCO). Our results show that the steroidogenic gene network is dysregulated in granulosa-lutein cells from women with either ovPCO or anovPCOS. Similarly, changes are also seen in androgen receptor expression and in the expression of some of its splice-variants. RNA-Sequencing identified 21,175 genes in granulosa-lutein cells with women with PCOS showing a distinct, global transcriptional profile of 450 differentially expressed genes. Subsequent pathway and network analyses highlighted a group of differentially expressed genes involved in cholesterol biosynthesis and metabolism that are highly enriched in women with PCOS. Finally, granulosa-lutein cells were cultured in the presence or absence of androgen, and the results suggest that changes in gene expression in women with PCOS may be, at least in part, a function of androgen action.


Granulosa cells play a major role in ovarian steroid synthesis including estrogen and progesterone. The significance of altered expression of genes involved in steroid and cholesterol metabolism remains to be fully elucidated, but these results lend further support to the notion of aberrant metabolic and endocrine function in granulosa cells of women with PCOS.