Background Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids.
Methods Pregnant women with mild asthma (n=52), moderate–severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed.
Results Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=−0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRα protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment.
Conclusions The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.
- Glucocorticoid receptor
- birth weight
- inhaled corticosteroid treatment
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Funding This work was supported by the National Health and Medical Research Council of Australia (NHMRC, ID 252438 and ID 565347), Asthma Foundation of NSW, the University of Newcastle and the Mothers and Babies Research Centre. Support was also provided from New South Wales Health through the Hunter Medical Research Institute. VLC was the recipient of the Arthur Wilson Memorial Scholarship from the Royal Australian College of Obstetricians and Gynaecologists and an NHMRC Senior Fellowship (ID 510703). VEM was the recipient of a National Health and Medical Research Council Dora Lush (Biomedical) Postgraduate Scholarship and a Hunter Medical Research Institute/Port Waratah Coal Services Postdoctoral Fellowship.
Competing interests PG has received expense reimbursement for lectures given in educational symposia sponsored by GlaxoSmithKline, AstraZeneca and Novartis. He has conducted research sponsored by GlaxoSmithKline and Pharmaxis. The other authors declare no competing interests.
Ethics approval This study was conducted with the approval of the Hunter New England Health and the University of Newcastle Human Research Ethics Committees.
Provenance and peer review Not commissioned; externally peer reviewed.
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