Hans Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Else Kröner-Forschungskolleg AntiAge, Bad Homburg, Germany.
Stress. 2020 Mar;23(2):233-242. doi: 10.1080/10253890.2019.1652266. Epub 2019 Aug 30.
Maternal stress, especially during early pregnancy, predisposes offspring to neuropsychiatric disorders. We hypothesized that maternal psychosocial stress (MPS) during pregnancy affects fetal structural neurodevelopment depending on the gestational age of exposure. Fetal sheep brains were harvested at 130 days gestation (dG, term 150 dG) from ewes frequently isolated from flock-mates during early gestation (first and second trimester; = 10) or late gestation (third trimester; = 10), or from control flock-mates ( = 8). Immunohistochemistry for formation of neuronal processes, myelination, synaptic density, cell proliferation and programed cell death was performed on brain tissue sections. Sections of the cortical gray matter, the hippocampal CA3 region and the superficial, subcortical and deep white matter were examined morphometrically. Stress effects depended on the brain region and time of exposure. Stress during early gestation but not during late gestation reduced the amount of neuronal processes in the cerebral cortex and hippocampus by 36.9 ± 10.1% ( < 0.05, mean ± SEM) and 36.9 ± 15.8% ( < 0.05), respectively, accompanied by a decrease in synaptic density in the cerebral cortex and hippocampus by 39.8 ± 23.1% ( < 0.05) and 32.9 ± 13.4% ( < 0.01). Myelination was decreased in white matter layers on average by 44.8 ± 11.7% ( < 0.05) accompanied by reduced (glial) cell proliferation in the deep white matter by 83.6 ± 12.4% ( < 0.05). In contrast, stress during the third trimester had no effect in any brain region. Chronic MPS during the first and second trimester induced prolonged effects on neuronal network and myelin formation which might contribute to disturbed neurobehavioral, cognitive and motor development in offspring of stressed mothers.Lay summaryMany women are exposed to stressful events during pregnancy. Maternal stress especially during early pregnancy predisposes for offspring's neuropsychiatric disorders. In our sheep study, we show that disturbance of fetal brain development is a potential mechanism and is worst during 1st and 2nd trimester.
母体应激，尤其是妊娠早期的应激，使后代易患神经精神疾病。我们假设妊娠期间母体心理社会应激（MPS）会根据暴露的胎龄影响胎儿结构神经发育。从妊娠 130 天（term 150dG）的母羊中收获胎羊大脑，这些母羊在妊娠早期（第一和第二孕期；n=10）或妊娠晚期（第三孕期；n=10）经常与羊群伙伴隔离，或来自对照羊群伙伴（n=8）。对脑组织切片进行神经元突起形成、髓鞘形成、突触密度、细胞增殖和程序性细胞死亡的免疫组织化学染色。对皮质灰质、海马 CA3 区以及浅层、皮质下和深层白质进行形态计量学检查。应激的影响取决于脑区和暴露时间。妊娠早期的应激而不是妊娠晚期的应激使大脑皮质和海马的神经元突起数量减少 36.9±10.1%（<0.05，平均值±SEM）和 36.9±15.8%（<0.05），同时大脑皮质和海马的突触密度分别减少 39.8±23.1%（<0.05）和 32.9±13.4%（<0.01）。白质层的髓鞘形成平均减少 44.8±11.7%（<0.05），同时深层白质的（神经胶质）细胞增殖减少 83.6±12.4%（<0.05）。相比之下，妊娠晚期的应激在任何脑区均无影响。妊娠第一和第二孕期的慢性 MPS 导致神经元网络和髓鞘形成的长期影响，这可能导致应激母亲的后代出现神经行为、认知和运动发育障碍。
非专业人士译文
许多女性在怀孕期间都会经历压力事件。母体压力，特别是妊娠早期的压力，会使后代易患神经精神疾病。在我们的绵羊研究中，我们发现胎儿大脑发育障碍是一种潜在的机制，在妊娠第一和第二孕期最为严重。
