Sex-specific difference in placental inflammatory transcriptional biomarkers of maternal phthalate exposure: a prospective cohort study

Previous epidemiologic research has shown that phthalate exposure in pregnant women is related to birth outcomes in a sex-specific manner. These outcomes may be mediated by placental inflammation, which is the proposed biological mechanism. This is the first study to address the relationship between phthalate exposure and gene expression in placental inflammation in a sex-specific manner. We performed quantitative PCR to measure placental inflammatory mRNAs (CRP, TNF-alpha, IL-1 beta, IL-6, IL-10, MCP-1, IL-8, CD68, and CD206) in 2469 placentae that were sampled at birth. We estimated the associations between mRNA and urinary phthalate monoesters using multiple linear regression models. Mono-n-butyl phthalate (MBP) was correlated with higher IL-1 beta, IL-6, and CRP expression in placentae of male fetuses and with higher IL-6, CRP, MCP-1, IL-8, IL-10, and CD68 expression in placentae of female fetuses. Mono benzyl phthalate (MBzP) increased the expression of TNF-alpha, MCP-1, and CD68 only in placentae of male fetuses. Mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively correlated with CRP, MCP-1, and CD68 in placentae of female fetuses. Maternal phthalate exposure was associated with inflammatory variations in placental tissues. The associations were stronger in placentae of male than of female fetuses. Compared with the other metabolites, MBP plays a strong role in these associations. The placenta is worth being further investigated as a potential mediator of maternal exposure-induced disease risk in children.