Abnormal fetomaternal glucocorticoid metabolism in the background of premature delivery: placental expression patterns of the 11-beta-hydroxysteroid dehydrogenase 2 gene

Abstract

OBJECTIVE: During pregnancy, 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is involved in the development of the placental barrier, and its main function is to protect the fetus from the effects of the physiological increase of maternal glucocorticoids. We compared human placental gene expression patterns of 11β-HSD2 from pregnancies that ended with preterm delivery versus full term pregnancies as controls.

STUDY DESIGN: We used real-time PCR to assess the placental gene expression patterns of 11β-HSD2 in 104 preterm and 140 full term pregnancies (control group) at the time of delivery.

RESULTS: In the preterm delivery group, the proportion of smokers was 26.9%, significantly higher than in the control group. Preterm delivery began with premature rupture of membranes in 70.2% and spontaneous uterine activity in 29.8%. The 11β-HSD2 gene was underexpressed in the preterm delivery group compared to normal pregnancy between 28 and 36 gestational weeks, but unchanged between 24 and 28 weeks. There was no fetal gender effect on 11β-HSD2 gene expression.

CONCLUSION: The reduced activity of the 11β-HSD2 gene seen in the preterm delivery group may impair fetal defences against maternal glucocorticoid exposure. In cases of impending premature delivery, glucocorticoid effects, potentially including postnatal neurological abnormalities and growth restriction, may be worsened by prophylactic steroids given to accelerate fetal lung maturity. The impairment in fetal defences against maternal glucocorticoids due to reduced 11β-HSD2 enzyme activity appears to begin after gestational week 28.