Department of Psychiatry, University of Colorado School of Medicine Anschutz Medical Campus, Aurora, CO, USA.
Department of Psychiatry, University of Colorado - Anschutz Medical Campus, 1890 N. Revere Court, Aurora, CO, 80045, USA.
Biol Sex Differ. 2023 Feb 17;14(1):7. doi: 10.1186/s13293-023-00492-0.
The mechanisms by which parental early life stress can be transmitted to the next generation, in some cases in a sex-specific manner, are unclear. Maternal preconception stress may increase susceptibility to suboptimal health outcomes via in utero programming of the fetal hypothalamic-pituitary-adrenal (HPA) axis.
We recruited healthy pregnant women (N = 147), dichotomized into low (0 or 1) and high (2+) adverse childhood experience (ACE) groups based on the ACE Questionnaire, to test the hypothesis that maternal ACE history influences fetal adrenal development in a sex-specific manner. At a mean (standard deviation) of 21.5 (1.4) and 29.5 (1.4) weeks gestation, participants underwent three-dimensional ultrasounds to measure fetal adrenal volume, adjusting for fetal body weight (FAV).
At ultrasound 1, FAV was smaller in high versus low ACE males (b = - 0.17; z = - 3.75; p < .001), but females did not differ significantly by maternal ACE group (b = 0.09; z = 1.72; p = .086). Compared to low ACE males, FAV was smaller for low (b = - 0.20; z = - 4.10; p < .001) and high ACE females (b = - 0.11; z = 2.16; p = .031); however, high ACE males did not differ from low (b = 0.03; z = .57; p = .570) or high ACE females (b = - 0.06; z = - 1.29; p = .196). At ultrasound 2, FAV did not differ significantly between any maternal ACE/offspring sex subgroups (ps ≥ .055). Perceived stress did not differ between maternal ACE groups at baseline, ultrasound 1, or ultrasound 2 (ps ≥ .148).
We observed a significant impact of high maternal ACE history on FAV, a proxy for fetal adrenal development, but only in males. Our observation that the FAV in males of mothers with a high ACE history did not differ from the FAV of females extends preclinical research demonstrating a dysmasculinizing effect of gestational stress on a range of offspring outcomes. Future studies investigating intergenerational transmission of stress should consider the influence of maternal preconception stress on offspring outcomes.
父母早年生活压力可以通过胎儿下丘脑-垂体-肾上腺（HPA）轴的宫内编程，以某种特定性别方式传递给下一代，其机制尚不清楚。母亲孕前压力可能通过胎儿 HPA 轴的宫内编程增加对次优健康结果的易感性。
我们招募了健康孕妇（N=147），根据 ACE 问卷将其分为低（0 或 1）和高（2+）不良童年经历（ACE）组，以检验母亲 ACE 史是否以特定性别方式影响胎儿肾上腺发育的假设。在平均（标准差）为 21.5（1.4）和 29.5（1.4）周妊娠时，参与者接受了三维超声检查以测量胎儿肾上腺体积，同时调整了胎儿体重（FAV）。
在超声检查 1 时，高 ACE 男性的 FAV 小于低 ACE 男性（b=-0.17；z=-3.75；p<0.001），但女性的 FAV 没有因母亲 ACE 组而异（b=0.09；z=1.72；p=0.086）。与低 ACE 男性相比，低 ACE（b=-0.20；z=-4.10；p<0.001）和高 ACE 女性（b=-0.11；z=2.16；p=0.031）的 FAV 更小；然而，高 ACE 男性与低 ACE（b=0.03；z=0.57；p=0.570）或高 ACE 女性（b=-0.06；z=-1.29；p=0.196）的 FAV 没有差异。在超声检查 2 时，母亲 ACE/后代性别的任何亚组之间的 FAV 均无显著差异（p≥0.055）。基线、超声检查 1 或超声检查 2 时，母亲 ACE 组之间的感知压力无显著差异（p≥0.148）。
我们观察到母亲 ACE 史较高对 FAV（胎儿肾上腺发育的代表）有显著影响，但仅在男性中。我们观察到，具有高 ACE 病史的母亲的男性 FAV 与女性的 FAV 没有差异，这延伸了产前应激对一系列后代结局产生雄性化作用的临床前研究。未来研究应考虑母亲孕前压力对后代结局的影响，以调查压力的代际传递。
