Antenatal exposure to betamethasone induces placental 11β-hydroxysteroid dehydrogenase type 2 expression and the adult metabolic disorders in mice.
Antenatal exposure to betamethasone induces placental 11β-hydroxysteroid dehydrogenase type 2 expression and the adult metabolic disorders in mice.
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产前接触倍他米松会诱导小鼠胎盘 11β-羟基类固醇脱氢酶 2 型表达和成年代谢紊乱。
DOI：
10.1371/journal.pone.0203802
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Zou C
中科院分区：
文献类型：
--
作者：
Ni L;Pan Y;Tang C;Xiong W;Wu X;Zou C
产前过度暴露于糖皮质激素会导致胎儿宫内生长受限（IUGR）和成人代谢紊乱。11β-羟基类固醇脱氢酶（11β-HSD） 1和2是糖皮质激素代谢的关键酶，然而，产前过度暴露糖皮质激素对胎盘11β-HSD1和2表达和成人代谢紊乱的详细影响尚不清楚。本文报道，在胎盘中，11β-HSD1是弥漫性的，而11β-HSD2在迷路层特异性表达。倍他米松使孕鼠胎盘11β-HSD2的表达显著增加，而11β-HSD1的表达不显著增加，胎儿体重下降，但胎盘体重没有下降。产前接触倍他米松会导致小于10周的幼仔体重明显下降，或者大于14周的幼仔体重增加。此外，产前暴露于倍他米松会导致成年后代共存各种代谢紊乱，包括高血糖、葡萄糖耐受不良、胰岛素分泌能力低下和高脂血症。本研究表明，孕鼠暴露于倍他米松可诱导胎盘11β-HSD2而非11β-HSD1的表达，导致胎儿IUGR并导致成人代谢紊乱，为成人疾病的胎儿起源及胎盘11β-HSD2在其中的潜在作用提供了证据。
Antenatal overexposure to glucocorticoids causes fetal intrauterine growth restriction (IUGR) and adult metabolic disorders. 11β-hydroxysteroid dehydrogenase (11β-HSD) 1 and 2 are key enzymes for glucocorticoid metabolism, however, the detailed effects of antenatal overexposure to glucocorticoids on placental 11β-HSD1 and 2 expression and adult metabolic disorders remain obscure. Here, we report that, in placenta 11β-HSD1 is diffusely localized, whereas 11β-HSD2 is specifically expressed in labyrinthine layer. Exposure of pregnant dams to betamethasone significantly increases the expression of placental 11β-HSD2 but not 11β-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 11β-HSD2 but not 11β-HSD1, leads to fetal IUGR and causes adult metabolic disorders, providing evidence for fetal origins of adult diseases and the potential role of placental 11β-HSD2 in them.
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有机素破坏了11beta-羟基甾体脱氢酶2型糖皮质激素的局部失活。
影响因子：
10.4
作者：
Atanasov, Atanas G;Nashev, Lyubomir G;Tam, Steven;Baker, Michael E;Odermatt, Alex
通讯作者：
Odermatt, Alex
影响因子：
3.7
作者：
Gathercole LL;Morgan SA;Bujalska IJ;Hauton D;Stewart PM;Tomlinson JW
通讯作者：
Tomlinson JW
影响因子：
2.1
作者：
Achard, Vincent;Boullu-Ciocca, Sandrine;Grino, Michel
通讯作者：
Grino, Michel
影响因子：
5.8
作者：
Murphy, VE;Zakar, T;Clifton, VL
通讯作者：
Clifton, VL
影响因子：
4.8
作者：
Brown, RW;Diaz, R;Seckl, JR
通讯作者：
Seckl, JR