Center for the Study of Fetal Programming, University of Wyoming, Laramie, WY, USA.
Am J Obstet Gynecol. 2013 Mar;208(3):217.e1-8. doi: 10.1016/j.ajog.2012.12.014. Epub 2012 Dec 7.
Synthetic glucocorticoid (sGC) administration to women threatening preterm delivery increases neonatal survival. Evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation programs offspring development. We examined fetal sGC multigenerational effects on F1 and F2 female offspring hypothalamo-pituitary-adrenal axis (HPAA) function.
At 0.7 gestation, pregnant F0 ewes received 4 dexamethasone injections (2 mg, approximately 60 μg/kg(-1) per day(-1), 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal HPAA function was tested in F1 and F2 ewes.
F1 and F2 ewe lambs showed reduced birthweight and morphometrics. Dexamethasone increased baseline but reduced stimulated HPAA activity in F1 and F2 female offspring.
This is the first demonstration that sGC doses in the clinical range have multigenerational effects on hypothalamo-pituitary-adrenal activity in a precocial species, indicating the need for the study of long-term effects of fetal sGC exposure.
对有早产风险的孕妇给予合成糖皮质激素（sGC）可提高新生儿存活率。有证据表明，胎儿暴露于高于当前成熟方案所设定的糖皮质激素水平会影响后代的发育。我们研究了胎儿 sGC 对子代下丘脑-垂体-肾上腺轴（HPAA）功能的多代影响。
在妊娠 0.7 天时，给 F0 孕羊注射 4 次地塞米松（2 mg，每天约 60 μg/kg(-1)，每 12 小时一次）或生理盐水（对照）。F1 雌性后代与雄性后代交配，产生 F2 雌性后代。在 F1 和 F2 母羊的青春期后检测 HPAA 功能。
F1 和 F2 母羊羔的出生体重和形态学指标降低。地塞米松增加了 F1 和 F2 雌性后代的基础 HPAA 活性，但减少了刺激后的 HPAA 活性。
这是首次证明临床剂量的 sGC 对子代中早熟物种的下丘脑-垂体-肾上腺活性具有多代影响，表明需要研究胎儿 sGC 暴露的长期影响。
