Impacts of maternal excess adiposity on the uterine immune environment: contributions to placental dysfunction and adverse pregnancy outcomes

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 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 findings from recent periconceptional immunophenotyping studies and outline important areas for future investigation in this field. 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.