Department of Obstetrics and Division of 'Experimental Obstetrics̔, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
Department of Biochemistry and Biomedical Sciences, Obstetrics & Gynecology and Pediatrics, Farncombe Family Digestive Health Research Institute, McMaster University, Main Street West, Ontario L8S4L8, Hamilton, 1280, Canada.
Placenta. 2018 Sep;69:9-19. doi: 10.1016/j.placenta.2018.07.007. Epub 2018 Jul 11.
We have previously shown that even a single course of antenatal betamethasone (BET) as an inductor for lung maturity reduces birth weight and head circumference. Moreover, animal studies link BET administration to alterations of the hypothalamic-pituitary-adrenal-gland-axis (HPA). The unhindered development of the fetal HPA axis is dependent on the function and activity of 11β-hydroxysteroiddehydrogenase type 2 (11β-HSD2), a transplacental cortisol barrier. Therefore, we investigated the effects of BET on this transplacental barrier and fetal growth.
Pregnant women treated with a single course of BET between 23 + 5 to 34 + 0 weeks of gestation were compared to gestational-age-matched controls. Placental size and neonatal anthropometrics were taken. Cortisol and ACTH levels were measured in maternal and umbilical cord blood samples. Placental 11β-hydroxysteroiddehydrogenase type 1 (11β-HSD1) protein levels and 11β-HSD2 protein and activity levels were determined. Parameters were analyzed independent of sex, and in subgroups divided by gender and gestational age.
In term born females, BET administration was associated with reduced head circumference and decreased 11β-HSD2 protein levels and enzyme activity. Males treated with BET, especially those born prematurely, showed increased 11β-HSD2 protein levels.
A single course of BET alters placental glucocorticoid metabolism in a sex-specific manner. Decreased 11β-HSD2 levels in term born females may lead to an increased placental transfer of maternal cortisol and therefore result in a reduced head circumference and a higher risk for altered stress response in adulthood. Further research is needed to conclude the significance of increased 11β-HSD2 levels in males.
我们之前已经表明，即使是单次产前倍他米松（BET）治疗作为肺成熟诱导剂，也会降低出生体重和头围。此外，动物研究将 BET 给药与下丘脑-垂体-肾上腺轴（HPA）的改变联系起来。胎儿 HPA 轴的不受阻碍的发育依赖于 11β-羟甾脱氢酶 2（11β-HSD2）的功能和活性，这是一种胎盘皮质醇屏障。因此，我们研究了 BET 对这种胎盘屏障和胎儿生长的影响。
将接受单次 BET 治疗的孕妇（妊娠 23+5 至 34+0 周）与胎龄匹配的对照组进行比较。测量胎盘大小和新生儿人体测量学参数。测量母血和脐血样本中的皮质醇和 ACTH 水平。测定胎盘 11β-羟甾脱氢酶 1（11β-HSD1）蛋白水平和 11β-HSD2 蛋白和活性水平。分析参数独立于性别，并按性别和胎龄分组进行亚组分析。
在足月出生的女性中，BET 给药与头围减小和 11β-HSD2 蛋白水平和酶活性降低有关。接受 BET 治疗的男性，尤其是那些早产的男性，显示出 11β-HSD2 蛋白水平升高。
单次 BET 治疗以性别特异性方式改变胎盘糖皮质激素代谢。足月出生女性 11β-HSD2 水平降低可能导致母体皮质醇向胎盘的转移增加，从而导致头围减小和成年后应激反应改变的风险增加。需要进一步研究才能得出男性 11β-HSD2 水平升高的意义。
