Reproduction Abstracts

Background: The human endometrium is a dynamic, multi-cellular sex steroid-dependent tissue subject to cyclical episodes of breakdown (menses), repair and regeneration. The mechanisms responsible for initiation of menses are well characterised; the molecular and cellular changes responsible for rapid repair are poorly understood. Re-epithelialisation of the tissue is thought to involve contributions from both the stromal and epithelial compartments. A role for androgens in endometrial repair has not been elucidated.

Methods: Artificial ‘menstrual’ cycles were induced in mice: ovariectomised mice were treated with oestradiol (E₂) and progesterone (P) and decidualisation was induced on day 8. Endometrial breakdown was initiated by removing the P pellet, 90 h after oil injection. Mice were given a single injection of DHT at the time of P withdrawal. A PCR array was utilised to investigate the effect of DHT on genes known to regulate mesenchymal–epithelial transition (MET), chromatin immunoprecipitation (chIP) allowed investigation of direct regulation by the androgen receptor.

Results and discussion: Evidence for a delayed onset of ‘menses’ was observed in DHT-treated animals. Treatment with DHT was associated with reduced concentrations of mRNAs encoded by genes involved in cellular remodelling, cell adhesion and cell matrix. Preliminary chIP analysis has identified a candidate set of MET-related genes that contain an androgen response element and therefore may be directly regulated by DHT. These studies implicate androgens in regulating genes involved in endometrial remodelling and repair which suggests that disturbances to peripheral androgen levels may contribute to the aetiology of the endometrial disorder, heavy menstrual bleeding.