Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

Regulatory effects of GR Exon 1 variants on differential placental glucocorticoid receptor protein isoform in pregnancies complicated with Asthma (#358)

Zarqa Saif 1 , Christian Corias 1 , Adele Evans 1 , Suyinn Chong 1 , Vicki L Clifton 1
  1. Mater Medical Research Institute, Woolloon Gabba, Brisbane, QUEENSLAND, Australia

Maternal asthma is the most common chronic diseases effecting 4-8% of the pregnancies. Sex specific differences in fetal growth and development outcomes are associated with maternal asthma. Adverse fetal outcomes are related with perturbation of the intrauterine environment and increased exposure to circulating glucocorticoids (GCs). Glucocorticoid receptors (GR) mediate GCs function. We have identified several GR isoforms expressed in placenta in relation to fetal sex, gestational age and maternal asthma. Our data has shown increased expression of GrαA, GRαD3 and GRαC in female placentae with increased sensitivity to GCs, while male placentae had high GRβ, GR-A and GR-P expression, may be mediating GC resistance in the presence of maternal asthma. The mechanisms regulating differential GR isoforms expression are unclear. GR exon1 variants are proposed to be modulating these mechanisms. Current study aimed to determine GR exon 1 variant expression in placentae of asthmatic pregnancies.

Placental mRNA from 100 control and asthmatic pregnancies was used to quantify different GR exon1 variants expression.

GR exon 1A, 1B, 1C, 1D, 1E, 1F, 1H, 1J and GR hnRNA expression was analysed in relation to clinical parameters and placental GR isoform. A sex specific change in GR exon variant 1B, 1C and 1F (P >0.001) expression in male placentae of asthmatic pregnancies was observed. However, GR exon 1D variant expression was higher (P >0.05) in females only. Cytosolic GRβ is positively correlated with variant 1C, 1H, while nuclear GRβ in male placentae was correlated with variant 1I. GRα-A isoform expression was significantly correlated with variant 1I expression in females. Variant 1D was positively correlated with GRα-D1 and D3. GR isoform 60kDa and 38kDa in cytosol were positively correlated with 1B, 1C, 1H, 1I and 1F variants.

Sex specific differences in placental GR isoform expression may be determined by the differential GR exon1 variants expression.