Department of Pediatrics, Women and Infants' Hospital of Rhode Island, Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI, 02905, USA.
Semin Immunopathol. 2016 Nov;38(6):699-708. doi: 10.1007/s00281-016-0579-8. Epub 2016 Jun 23.
Pregnancy represents a period of physiological stress, and although this stress is experienced for a very modest portion of life, it is now recognized as a window to women's future health, often by unmasking predispositions to conditions that only become symptomatic later in life. In normal pregnancy, the mother experiences mild metabolic syndrome-like condition through week 20 of gestation. A pronounced phenotype of metabolic syndrome may program pregnancy complications such as preeclampsia. Preeclampsia is a serious complication with a myriad of manifestations for mother and offspring. This pregnancy syndrome is a polygenic disease and has been now linked to higher incidence of cardiovascular disease, diabetes, and several other disorders associated with vulnerable organs. Furthermore, the offspring born to preeclamptic mothers also exhibit an elevated risk of cardiovascular disease, stroke, and mental disorders during adulthood. This suggests that preeclampsia not only exposes the mother and the fetus to complications during pregnancy but also programs chronic diseases in later life. The etiology of preeclampsia is thought to be primarily associated with poor placentation and entails excessive maternal inflammation and endothelial dysfunction. It is well established now that the maternal immune system and the placenta are involved in a highly choreographed cross-talk that underlies adequate spiral artery remodeling required for uteroplacental perfusion and free flow of nutrients to the fetus. Since normal pregnancy is associated with a sequence of events represented by temporal events of inflammation (implantation), anti-inflammation (gestation), and inflammation (parturition), it is quite possible that unscheduled alterations in these regulatory responses may lead to pathologic consequences. Although it is not clear whether immunological alterations occur early in pregnancy, it is proposed that dysregulated systemic and placental immunity contribute to impaired angiogenesis and the onset of preeclampsia. This review will focus on important aspects of the immune system that coordinate with placental dysfunction to program preeclampsia and influence health in later life.
妊娠是一段生理压力期，虽然这种压力只在人生的一小段时间内经历，但现在人们认识到它是女性未来健康的一个窗口，常常揭示了以后生活中出现症状的疾病倾向。在正常妊娠中，母亲在妊娠 20 周前会经历轻度类似于代谢综合征的状态。代谢综合征的明显表型可能会引发子痫前期等妊娠并发症。子痫前期是一种严重的并发症，会给母亲和胎儿带来多种表现。这种妊娠综合征是一种多基因疾病，现已与心血管疾病、糖尿病和其他几种与脆弱器官相关的疾病的发病率升高有关。此外，子痫前期母亲所生的后代在成年期也表现出更高的心血管疾病、中风和精神障碍风险。这表明子痫前期不仅使母亲和胎儿在妊娠期间面临并发症风险，还会导致以后生活中的慢性疾病。子痫前期的病因主要与胎盘不良有关，涉及母体过度炎症和内皮功能障碍。现在已经确定，母体免疫系统和胎盘参与了高度协调的对话，这是螺旋动脉充分重塑所必需的，以保证胎盘灌注和营养物质向胎儿自由流动。由于正常妊娠伴随着一系列事件，包括炎症（着床）、抗炎（妊娠）和炎症（分娩）的时间事件，因此很有可能这些调节反应的意外改变会导致病理后果。虽然尚不清楚免疫改变是否发生在妊娠早期，但有人提出，系统性和胎盘免疫失调会导致血管生成受损和子痫前期的发生。这篇综述将重点介绍免疫系统的重要方面，这些方面与胎盘功能障碍协同作用，引发子痫前期，并影响以后的健康。
