Gross Moshe, Romi Hava, Gilimovich Yelena, Drori Elyashiv, Pinhasov Albert
Department of Molecular Biology, Ariel University, Ariel, Israel.
Department of Chemical Engineering and Biotechnology, Ariel University, Ariel, Israel.
Stress. 2018 Nov;21(6):474-483. doi: 10.1080/10253890.2018.1460660. Epub 2018 Apr 12.
Prenatal stress may increase concentrations of maternal glucocorticoids, which restrict fetal growth, with variable impact upon postnatal development. Among key regulators of stress hormone effects are the glucocorticoid receptor (GR) and 11β-hydroxysteroid dehydrogenase-2 (11βHSD2), the enzyme that inactivates glucocorticoid. This study utilized mice selectively bred for social dominance (Dom) or submissiveness (Sub), respectively exhibiting resilience or sensitivity to stress, to test whether stress-induced alterations in placental GR and 11βHSD2 protein expression may mediate divergent effects of prenatal adversity upon postnatal development. Pregnant Dom and Sub dams underwent prenatal restraint stress (PRS) for 45 min on gestational days (GD) 15-17. PRS induced a similar spike in serum corticosterone concentrations of dams from each strain on GD15 ( < .001, = 8), and impaired fetal growth ( < .01, = 5 litters), although Dom placentae were larger than Sub placentae ( < .01). Among placentae from Dom dams, PRS elevated protein contents of both GR ( < .05, = 5 litters) and 11βHSD2 ( < .01) on GD19. In contrast, GR contents were reduced among placentae from PRS-exposed Sub mice ( < .01), without changes in 11βHSD2 content. Correspondingly, Dom PRS pup growth recovered by PND14, yet Sub PRS pups remained underweight into adolescence ( < .0001, = 40 pups). Thus, prenatal stress more strongly increased placental GR and 11βHSD2 levels among Dom mice than in Subs. Increased GR may improve placental function and up-regulate 11βHSD2 expression, protecting fetuses from effects of prenatal stress upon postnatal development. Placental recruitment of GR and 11βHSD2 are potential markers of stress-induced developmental disorders, in accordance with maternal resilience or sensitivity to stress.
产前应激可能会增加母体糖皮质激素的浓度，这会限制胎儿生长，并对产后发育产生不同影响。应激激素效应的关键调节因子包括糖皮质激素受体（GR）和11β-羟基类固醇脱氢酶-2（11βHSD2），后者是使糖皮质激素失活的酶。本研究利用分别为社会主导型（Dom）或顺从型（Sub）而选择性培育的小鼠，它们分别表现出对压力的恢复力或敏感性，以测试应激诱导的胎盘GR和11βHSD2蛋白表达变化是否可能介导产前逆境对产后发育的不同影响。怀孕的Dom和Sub母鼠在妊娠第15 - 17天接受45分钟的产前束缚应激（PRS）。PRS在妊娠第15天使各品系母鼠的血清皮质酮浓度出现类似的峰值（<0.001，n = 8），并损害胎儿生长（<0.01，n = 5窝），尽管Dom胎盘比Sub胎盘大（<0.01）。在Dom母鼠的胎盘中，PRS在妊娠第19天提高了GR（<0.05，n = 5窝）和11βHSD2（<0.01）的蛋白含量。相比之下，暴露于PRS的Sub小鼠的胎盘中GR含量降低（<0.01），而11βHSD2含量没有变化。相应地，Dom PRS幼崽在出生后第14天体重恢复，但Sub PRS幼崽在进入青春期时仍体重不足（<0.0001，n = 40只幼崽）。因此，产前应激在Dom小鼠中比在Sub小鼠中更强烈地增加胎盘GR和11βHSD2水平。GR增加可能改善胎盘功能并上调11βHSD2表达，保护胎儿免受产前应激对产后发育的影响。根据母体对压力的恢复力或敏感性，胎盘对GR和11βHSD2的募集是应激诱导发育障碍的潜在标志物。
