Bellissimo Christian J, Beristain Alexander G, Sloboda Deborah M
Reproduction. 2025 Jul 22;170(2). doi: 10.1530/REP-24-0464. Print 2025 Aug 1.
Maternal excess adiposity (i.e. overweight and obesity) increases the risk of obstetrical complications, adverse pregnancy outcomes, and chronic health conditions postnatally. These risks are partly rooted in poor placental development and function. Compositional and functional disturbances to uterine-resident immune cells are likely to contribute to the increased burden of placental malperfusion and inflammatory injury seen in pregnancies complicated by overweight and obesity. Here, we summarize the current knowledge surrounding how excess adiposity influences the tissue-resident immune milieu of the uterus during the periconceptional period and across gestation.
Dynamic compositional and functional changes in the uterine immune environment occur across pregnancy to support placental development and fetal growth. Parental exposures that modify the differentiation, trafficking, or effector functions of uterine-resident immune cells, including chronic health conditions, have been linked to placental dysfunction and the development of obstetrical complications. Overweight and obesity (i.e. excess adiposity) is the most common chronic condition affecting pregnant people in most Westernized countries and is associated with an increased risk of multiple obstetrical complications underpinned by poor placental development and function. Emerging evidence supports the notion that maternal excess adiposity is linked to an altered immune landscape at the uteroplacental interface beginning early in pregnancy. This likely contributes to the development of malperfusion and inflammatory injury that fuels placental dysfunction and primes for adverse pre- and postnatal outcomes. However, a comprehensive understanding of how maternal excess adiposity affects the uterine immune milieu is currently lacking, particularly during the critical stages of placental development. In this review, we provide a summary of current knowledge regarding the ontogeny and function of tissue-resident leukocytes at the uteroplacental interface, focusing on the major populations of innate immune cells that contribute to placental development in humans. We also discuss the impacts of maternal obesity on placental development and function, how these outcomes may be related to the findings from recent periconceptional immunophenotyping studies and outline important areas for future investigation in this field.
孕妇过度肥胖（即超重和肥胖）会增加产科并发症、不良妊娠结局以及产后慢性健康问题的风险。这些风险部分源于胎盘发育不良和功能异常。子宫内常驻免疫细胞的组成和功能紊乱可能导致超重和肥胖孕妇出现胎盘灌注不足和炎症损伤负担增加的情况。在此，我们总结了目前关于孕期肥胖如何在受孕前阶段及整个孕期影响子宫组织常驻免疫环境的相关知识。
孕期子宫免疫环境会发生动态的组成和功能变化，以支持胎盘发育和胎儿生长。包括慢性健康问题在内的改变子宫常驻免疫细胞分化、迁移或效应功能的母体暴露因素，已被证明与胎盘功能障碍和产科并发症的发生有关。超重和肥胖是大多数西方国家影响孕妇的最常见慢性病，与胎盘发育不良和功能异常导致的多种产科并发症风险增加有关。新出现的证据支持这样一种观点，即孕妇过度肥胖与妊娠早期子宫胎盘界面免疫格局的改变有关。这可能会导致灌注不足和炎症损伤的发生，进而引发胎盘功能障碍，并增加产前和产后不良结局的风险。然而，目前对于孕妇过度肥胖如何影响子宫免疫环境仍缺乏全面的了解，尤其是在胎盘发育的关键阶段。在这篇综述中，我们总结了目前关于子宫胎盘界面组织常驻白细胞的个体发育和功能的知识，重点关注对人类胎盘发育有贡献的主要固有免疫细胞群体。我们还讨论了孕妇肥胖对胎盘发育和功能的影响，这些结果如何与近期受孕前免疫表型研究的结果相关，以及概述了该领域未来重要的研究方向。
