Antenatal exposure to betamethasone induces placental 11β-hydroxysteroid dehydrogenase type 2 expression and the adult metabolic disorders in mice

作者：Ni, Li; Pan, Yibin; Tang, Chao; Xiong, Wenyi; Wu, Ximei^*; Zou, Chaochun^*

来源：PLos One, 2018, 13(9): e0203802.

DOI：10.1371/journal.pone.0203802

• BETA-HYDROXYSTEROID DEHYDROGENASE
• GLUCOCORTICOID-RECEPTOR PROTEIN
• MESSENGER-RNA
• MINERALOCORTICOID RECEPTOR
• DIFFERENTIAL EXPRESSION
• CUSHINGS-SYNDROME
• LATE PREGNANCY
• FETAL-GROWTH
• GLUCOSE
• CELLS

Antenatal overexposure to glucocorticoids causes fetal intrauterine growth restriction (IUGR) and adult metabolic disorders. 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 1 and 2 are key enzymes for glucocorticoid metabolism, however, the detailed effects of antenatal overexposure to glucocorticoids on placental 11 beta-HSD1 and 2 expression and adult metabolic disorders remain obscure. Here, we report that, in placenta 11 beta-HSD1 is diffusely localized, whereas 11 beta-HSD2 is specifically expressed in labyrinthine layer. Exposure of pregnant dams to betamethasone significantly increases the expression of placental 11 beta HSD2 but not 11 beta-HSD1, and decreases the weights of fetuses but not placentas. Antenatal exposure to betamethasone leads to either significant weight loss in the offspring younger than 10-week-old, or weight gain in those older than 14-week-old. Furthermore, antenatal exposure to betamethasone results in coexistence of various metabolic disorders in adult offspring, including hyperglycemia, glucose intolerance, low insulin secretory capacity and hyperlipidemia. The present study demonstrates that exposure of pregnant dams to betamethasone induces the expression of placental 11 beta-HSD2 but not 11 beta-HSD1, leads to fetal IUGR and causes adult metabolic disorders, providing evidence for fetal origins of adult diseases and the potential role of placental 11 beta-HSD2 in them.

• 出版日期2018-9-13
• 单位浙江大学