Doctoral Dissertation Research: Reproductive-immune trade-offs in preterm birth: a life history perspective

母亲与后代、生殖与免疫功能之间的进化权衡，很可能塑造了人类的生活史。这项研究将调查早产背景下的这种权衡，早产通常与轻度感染和/或炎症有关，表明生殖和免疫系统之间的生理妥协可能会影响妊娠时间。研究人员将在母体免疫挑战和早产的背景下评估胎盘特征，包括胎盘微生物组。项目发现可能会扩展目前有限的关于微生物组在人类生理和健康中的作用的知识，特别是在胎盘界面。在早产率方面，美国与南亚和撒哈拉以南非洲并列，种族、民族和社会经济地位差异极大。通过考虑免疫激活可能损害生殖的进化根源，该项目将为持续存在的公共卫生问题带来新的视角，并有可能为社区卫生工作和公共卫生政策提供信息。其他更广泛的影响包括本科培训和跨学科研究合作的促进。这项对美国妇女的研究将在基于生殖免疫权衡的进化生活史框架内整合母体状况、胎盘功能、胎盘微生物群和妊娠长度。研究人员将测试两个假设：1)胎盘表型以缩小的尺寸和效率为特征，以及独特的微生物组，将与早产有关；2)这种关联将取决于母体的全身炎症。这项研究的结果将揭示怀孕期间免疫激活的影响，并将推进胎盘微生物组功能和变异的进化观点，及其在早产中的作用。

Evolutionary tradeoffs between mother and offspring, and between reproduction and immune function, are likely to have shaped human life history. This study will investigate such tradeoffs in the context of preterm birth, which is frequently associated with mild infection and/or inflammation, suggesting that physiological compromises between reproduction and the immune system may influence gestation length. The investigators will evaluate placental characteristics, including the placental microbiome, in the context of maternal immune challenge and preterm birth. Project findings may extend current limited knowledge of the role of microbiomes in human physiology and health, specifically at the placental interface. The U.S. ranks alongside South Asia and Sub-Saharan Africa in rates of preterm birth, with extreme disparities based on race, ethnicity, and socioeconomic status. By considering the evolutionary roots of why immune activation might compromise reproduction, this project will bring a new perspective to a persistent public health problem, and has the potential to inform community health efforts and public health policy. Other broader impacts include undergraduate training and the fostering of interdisciplinary research collaborations.This study of U.S. women will integrate maternal condition, placental function, the placental microbiome, and gestation length within an evolutionary life history framework based on reproductive-immune trade-offs. The investigators will test two hypotheses: 1) that the placental phenotype characterized by reduced size and efficiency, and a distinct microbiome, will be associated with preterm birth, and 2) that this association will depend on maternal systemic inflammation. The results of this research will shed light on the effects of immune activation during pregnancy, and will advance evolutionary perspectives on placental microbiome function and variation, and its role in preterm birth.