Delayed endometrial decidualisation in polycystic ovary syndrome; the role of AR-MAGEA11

Kinza Younas, Marcos Quintela, Samantha Thomas, Jetzabel Garcia-Parra, Lauren Blake, Helen Whiteland, Adnan Bunkheila, Lewis W. Francis, Lavinia Margarit, Deyarina Gonzalez, R. Steven Conlan

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Abstract: Polycystic ovary syndrome (PCOS) is a common gynaecological disorder, with a prevalence of up to 12% of women of reproductive age, and is in part characterised by elevated circulating androgens and aberrant expression of androgen receptor (AR) in the endometrium. A high percentage of PCOS patients suffer from infertility, a condition that appears to be linked to mistimed and incomplete decidualisation critically affecting events surrounding embryo implantation. The aim of this study was to examine the involvement of MAGEA11, and the genome-wide role of AR in PCOS. We determined that elevated androgen levels on PCOS cells had an impact on the delayed and incomplete decidual transformation of endometrial cells. The AR co-regulator MAGEA11, a known enhancer of AR function, was constitutively overexpressed throughout the menstrual cycle of PCOS patients, co-localised in the nucleus of PCOS stromal tissue and cells and formed a molecular complex with AR. Genome-wide AR analysis in PCOS stromal cells revealed that AR targets included genes involved in cell death and apoptosis, as well as genes commonly dysregulated in endometrial cancer. Enhanced MAGEA11 and AR-mediated transcriptional regulation may impact on a correct endometrial decidualisation response, subsequently affecting endometrial receptivity in these infertile women. Key messages: MAGEA11 and AR are overexpressed in hyperandrogenic PCOS patients.MAGEA11-AR overexpression in PCOS correlates with delayed decidualisation.AR and MAGEA11 associate in a molecular complex.AR directly regulates a unique set of genes controlling gene differentiation.

Original languageEnglish (US)
Pages (from-to)1315-1327
Number of pages13
JournalJournal of Molecular Medicine
Volume97
Issue number9
DOIs
StatePublished - Sep 1 2019

Keywords

  • AR
  • Decidualisation
  • Delay
  • MAGEA11
  • PCOS

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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