The establishment of pregnancy requires dynamic remodelling of the endometrium. Decidualization, a key part of this process, is characterised by differentiation of endometrial stromal fibroblasts (ESF) which secrete factors that regulate implantation and placental development. We recently discovered that ESF synthesise androgens which modulate the expression of endometrial receptivity and decidualization markers. Utilisation of the circulating androgen precursor DHEA within target tissues requires local action of the enzyme 3β-hydroxysteroid dehydrogenase (3βHSD) which we have previously reported is expressed in ESF. Although DHEA is abundant in the circulation, whether changes in the bioavailability of DHEA can affect endometrial function is not known. We hypothesised that modulating the bioavailability of DHEA could alter local tissue androgen concentrations and impact on decidualization and endometrial receptivity. Primary human endometrial stromal cells were isolated from endometrial biopsies collected from women during the proliferative phase of the cycle (n=18). Decidualization was induced in vitro (Progesterone + cAMP); some cells were co-treated with DHEA or with the 3βHSD inhibitor trilostane. DHEA increased testosterone biosynthesis (P<0.001) and was associated with increased expression of the decidualization marker IGFBP1 (P<0.05). Trilostane significantly reduced biosynthesis of testosterone and secretion of IGFBP-1 (P<0.001) and decreased expression of the receptivity marker osteopontin (SPP1; P<0.01).These data demonstrate that changes in the bioavailability of DHEA impact on the expression of decidualization and endometrial receptivity markers. These findings suggest a previously unrecognised role for tissue androgen bioavailability in the regulation of the endometrium which may impact on the establishment of pregnancy in women.
Presenting author: Douglas Gibson, MRC Centre for Inflammation Research, The Queens Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ. Email: D.A.Gibson@ed.ac.uk.