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Understanding testosterone signalling in pregnancy to improve maternal, fetal and placental health
Excess androgens (hyperandrogenism) during pregnancy increases the risk of hypertension, preeclampsia, and fetal growth restriction (FGR). Preclinical and clinical studies show hyperandrogenic pregnancies present with immediate maternal and fetal risks, and increases cardiovascular disease (CVD) risks postpartum (maternal) and in later life (offspring). Although the aetiology of these risks remains unclear, disrupted placental development and function predicts both maternal and offspring vascular impairment, and thus CVD risk.
Therefore, characterising the intricate and dynamic relationship between maternal, placental, and fetal vascular components, understanding how complications of pregnancy impacts their interactions at molecular and functional physiological levels, and assessing the efficacy of targeted interventions to improve maternal-placental-fetal vascular function in hyperandrogenic pregnancies, is required.
Androgen signalling involves complex regulation, with tissue-specific androgen receptor (AR) variants modulating downstream pathways involved in vascular and immune function and growth. The truncated variant AR-45 inhibits the full-length AR (AR-FL), potentially exerting antiandrogenic effects. Hyperandrogenism increases AR-FL but decreases AR-45 expression in the placenta, leading to dysregulated angiogenic pathways. This imbalance may contribute to vascular impairments, and therefore increase CVD risks. Current clinical treatments for hyperandrogenism are not used during pregnancy due to teratogenic risk; however, nutritional supplements that exert antiandrogenic action may offer benefit.
This fellowship aims to explore AR-FL and AR-45 in maternal and fetal hearts, and placenta, using sheep models and human pregnancy cohorts. Molecular changes will be related to functional measures by MRI. Associations between placental androgen signalling, blood pressure, blood flow, and angiogenic factors will be examined to establish novel diagnostic markers of androgen signalling dysfunction. The efficacy of a nutritional supplement in normalizing androgen signalling and restoring maternal and offspring cardiovascular function will also be assessed.
Last updated09 May 2025
Last reviewed08 May 2025