ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 65 P353 | DOI: 10.1530/endoabs.65.P353

Differential expression in granulosa-lutein (GL) cells from polycystic ovaries of genes implicated in assembly and modification of extracellular matrix (ECM)

Kate Hardy, Thomas Hopkins, Avigdor Lerner, Orla Green & Stephen Franks

Imperial College, London, UK

Introduction: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women and polycystic ovaries are characterized by excess ovarian stroma that has implications for disordered follicle development in PCOS. The factors contributing to proliferation and increased density of stroma remain unclear but local overproduction of androgens may be involved.

Aim: To examine differential expression of genes that regulate key proteins that comprise ECM and, in particular, ECM-modifying genes that are involved in collagen processing.

Methods: From our database of 450 differentially expressed genes in GL cells (RNAseq) from 12 women with and 12 without PCOS, we manually identified genes (PubMed) that regulate synthesis and processing of ECM proteins.

Results: We found significant differential gene expression of 7 structural ECM molecules. Three collagens were downregulated (COL5A2, COL11A1 and COL4A1, a basal lamina protein, as was FREM2) and FBLN7 (Fibulin7). Two ECM genes were upregulated (COL21A1 and LAMA3). Importantly, 3 genes that post-translationally modify collagen were differentially expressed; PLOD2, P4HA2 and LEPREL1, as were LOX, which cross-links collagen, and MIA3, involved in collagen secretion. Two further genes involved in ECM remodelling, MMP19 and HPSE, were upregulated. In a parallel study of effects of dihydrotestosterone on mouse ovarian follicles, we have found evidence for androgen regulation of Coll11a1, Coll 4a1, Fbln7, Lama3, Plod2, HPSE and MMP19.

Conclusion: Genes that are important for assembly and, especially, processing of ECM molecules are differentially expressed in GL cells from PCOS women. These changes are likely to contribute to altered structure and function of the stromal component of polycystic ovaries and highlight signalling pathways for further investigation. There is evidence, from our animal studies, that some of these pathways are influenced by androgen signalling.

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