Inflammation and oxidative stress as mediators of the impacts of environmental exposures on human pregnancy: Evidence from oxylipins.

Inflammation and oxidative stress play major roles in healthy and pathological pregnancy. Environmental exposure to chemical pollutants may adversely affect maternal and fetal health in pregnancy by dysregulating these critical underlying processes of inflammation and oxidative stress. Oxylipins are bioactive lipids that play a major role in regulating inflammation and increasing lines of evidence point towards an importance in pregnancy. The biosynthetic production of oxylipins requires oxygenation of polyunsaturated fatty acids, which can occur through several well-characterized enzymatic and nonenzymatic pathways. This review describes the state of the science of epidemiologic evidence on oxylipin production in pregnancy and its association with 1) key pregnancy outcomes and 2) environmental exposures. We searched PubMed for studies of pregnancy that measured one or more oxylipin analytes during pregnancy or delivery. We evaluated oxylipin associations with three categories of adverse pregnancy outcomes, including preeclampsia, preterm birth, and fetal growth restriction, along with several categories of environmental pollutants. The majority of studies evaluated one to two oxylipins, most of which focused on oxylipins produced from nonenzymatic processes of oxidative stress. However, an increasing number of recent studies have leveraged technological advancements to profile a large number of oxylipins produced from distinct biosynthetic pathways. Although the literature indicated robust evidence that oxylipins produced via nonenzymatic pathways are associated with pregnancy outcomes and environmental exposures, evidence for enzymatically produced oxylipins showed that associations may differ between biosynthetic pathways. Along with summarizing this evidence, we review promising therapeutic options to regulate oxylipin production and provide a set of recommendations for future epidemiologic studies in these research areas. Further evidence is needed to improve our understanding of how oxylipins may act as key biological mediators for the adverse effects of environmental pollutants on pregnancy outcomes.