Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, United States.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, United States.
Front Immunol. 2020 Feb 26;11:254. doi: 10.3389/fimmu.2020.00254. eCollection 2020.
Maternal stress is a well-established risk factor for preterm birth and has been associated with adverse neonatal outcomes in the first and subsequent generations, including increased susceptibility to disease and lasting immunological changes. However, a causal link between prenatal maternal stress and preterm birth, as well as compromised neonatal immunity, has yet to be established. To fill this gap in knowledge, we used a murine model of prenatal maternal stress across three generations and high-dimensional flow cytometry to evaluate neonatal adaptive immunity. We report that recurrent prenatal maternal stress induced preterm birth in the first and second filial generations and negatively impacted early neonatal growth. Strikingly, prenatal maternal stress induced a systematic reduction in T cells and B cells, the former including regulatory CD4+ T cells as well as IL-4- and IL-17A-producing T cells, in the second generation. Yet, neonatal adaptive immunity gained resilience against prenatal maternal stress by the third generation. We also show that the rate of prenatal maternal stress-induced preterm birth can be reduced upon cessation of stress, though neonatal growth impairments persisted. These findings provide evidence that prenatal maternal stress causes preterm birth and affects neonatal immunity across generations, adverse effects that can be ameliorated upon cessation.
母体应激是早产的一个公认的风险因素，并与第一代和随后几代的不良新生儿结局相关，包括疾病易感性增加和持久的免疫变化。然而，产前母体应激与早产以及新生儿免疫功能受损之间的因果关系尚未确定。为了填补这一知识空白，我们使用了三代母鼠产前应激模型和高维流式细胞术来评估新生儿适应性免疫。我们报告说，反复的产前母体应激导致第一代和第二代出现早产，并对早期新生儿生长产生负面影响。引人注目的是，产前母体应激导致第二代 T 细胞和 B 细胞系统性减少，前者包括调节性 CD4+T 细胞以及产生 IL-4 和 IL-17A 的 T 细胞。然而，第三代新生儿适应性免疫对产前母体应激具有恢复力。我们还表明，一旦停止应激，产前母体应激引起的早产率可以降低，但新生儿生长受损仍然存在。这些发现提供了证据表明，产前母体应激会导致早产和跨代影响新生儿免疫，这些不利影响可以通过停止应激得到改善。
