The Center for the Study of Fetal Programming, Laramie, WY, USA.
Am J Obstet Gynecol. 2012 Sep;207(3):203.e1-8. doi: 10.1016/j.ajog.2012.06.024. Epub 2012 Jun 19.
Synthetic glucocorticoid administration to women threatening preterm delivery increases neonatal survival. However, mounting evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation adversely programs offspring development. We examined fetal synthetic glucocorticoid multigenerational metabolic effects on F1 and F2 female offspring.
At 0.7 gestation, pregnant F0 ewes received 4 injections of dexamethasone (2 mg, approximately 60 ug.kg(-1) day(-1) 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal pancreatic β-cell function was tested in F1 and F2 by intravenous glucose tolerance test.
F1 and F2 ewe lambs showed reduced birthweight and morphometrics, and similar increased fasting glucose and decreased intravenous glucose tolerance test β-cell response.
This is the first demonstration of multigenerational programming of later life β-cell response by clinically relevant doses of synthetic glucocorticoid indicating the need for study of long-term effects of fetal exposure to synthetic glucocorticoid.
对有早产风险的孕妇给予合成糖皮质激素可提高新生儿存活率。然而，越来越多的证据表明，胎儿暴露于高于当前成熟所需水平的糖皮质激素会对后代的发育产生不利影响。我们研究了胎儿合成糖皮质激素对子代 F1 和 F2 雌性后代的多代代谢影响。
在妊娠 0.7 天时，给怀孕的 F0 母羊注射 4 次地塞米松（2 mg，约 60ug/kg/天，12 小时一次）或生理盐水（对照）。F1 雌性后代繁殖产生 F2 雌性后代。通过静脉葡萄糖耐量试验测试 F1 和 F2 青春期后的胰腺β细胞功能。
F1 和 F2 母羊羔羊的出生体重和形态学均降低，空腹血糖升高，静脉葡萄糖耐量试验β细胞反应降低。
这首次证明了临床相关剂量的合成糖皮质激素对子代生命后期β细胞反应的多代编程，表明需要研究胎儿暴露于合成糖皮质激素的长期影响。
