Gene expression patterns of the 11β-hydroxysteroid dehydrogenase 2 enzyme in human placenta from intrauterine growth restriction: the role of impaired feto-maternal glucocorticoid metabolism

Abstract

OBJECTIVE: To assess 11-β-hydroxysteroid dehydrogenase 2 (11β-HSD2) gene expression patterns in human placental samples from intrauterine growth restriction (IUGR) pregnancies using normal pregnancy as control. STUDY DESIGN: We compared 11-β-HSD2 gene expression in placental samples from all IUGR pregnancies treated in our clinic between January 1, 2010 and January 1, 2011 vs. 140 normal pregnancy samples from the same study period. Clinical characteristics were also assessed and compared between the IUGR and normal pregnancy groups. RESULTS: Mean gestational weight gain in the IUGR group was significantly lower than in the control group. Similarly, change in body mass index (BMI) was lower. Impending intrauterine fetal asphyxia was significantly more common in the IUGR group. The 11β-HSD2 gene was underexpressed compared to controls, but this underexpression was only observed after the 33rd gestational week. Within the IUGR group, in cases of impending intrauterine fetal asphyxia the 11β-HSD2 gene was underexpressed compared to both impending asphyxia in non-IUGR cases, or IUGR without impending asphyxia. CONCLUSION: Low gestational weight gain appears to predict IUGR. The 11β-HSD2 gene in IUGR is underexpressed and may result in an impaired placental barrier, decreasing protection against maternal glucocorticoids, which are thought to be prominent in fetal programming. Maternal glucocorticoid exposure resulting from an impaired placental barrier may increase the risk for cardiovascular and metobolic disorders later in adult life. In IUGR, before the 33rd gestational week, the expression of the 11β-HSD2 gene remains physiological. The underexpression of this gene after the 33rd week in impending intrauterine fetal asphyxia in IUGR points to an increased sensitivity to hypoxia when impending asphyxia is present in the late phase of IUGR pregnancies.