The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Sex-specific placental androgen receptor isoform expression varies with maternal asthma and growth (#82)

Ashley S Meakin 1 , Zarqa Saif 1 , Vicki L Clifton 1
  1. Mater Medical Research Institute - University of Queensland, Woolloongabba, QLD, Australia

Androgen concentrations rise as gestation progresses in both the maternal and fetal circulations and may drive sex-specific differences in fetal growth, especially in the presence of an adverse environment. Males have increased birthweight compared to females in pregnancies complicated by asthma and we have proposed that males continue to grow under adverse conditions while females reduce growth due to a difference in androgen sensitivity. There are at least 20 different androgen receptor (AR) isoforms that may confer differences in androgen sensitivity. We have questioned whether the expression of these AR isoforms are detectable in the human placenta, whether they vary by cellular localisation, between the sexes, by birthweight, or in the presence or absence of maternal asthma. Placental protein (n=34 male, n=30 female) and mRNA (n=51 male, n=49 female) was used to identify AR protein isoform levels and downstream target gene expression. Protein and mRNA levels were analysed against multiple neonatal measurements to assess any relationships. Four known AR isoforms (AR-FL, AR-V1, AR-V7, and AR-45) were identified in the human placenta. Male placentae from asthmatic pregnancies had decreased nuclear AR-FL, 90 kDa, AR-V1, and AR-V7 protein expression, but increased AR-45 mRNA and protein. Nuclear AR-45 protein positively correlated with IGF1, IGF1R, and IGFBP5 mRNA expression. IGF1R, IGFBP3, IGFBP5, and VEGF mRNA was significantly higher in male placentae from asthmatic pregnancies. These differences in AR protein expression and downstream signalling targets may contribute to sex-specific differences in fetal growth in response to an adverse environment.