Maternal Phthalate and Personal Care Products Exposure Alters Extracellular Placental miRNA Profile in Twin Pregnancies

Abstract

Prenatal exposure to endocrine-disrupting chemicals (EDCs) exerts both short- and long-term adverse effects on the developing fetus. However, the mechanisms underlying these effects have yet to be uncovered. Maternal-fetal signaling is mediated in part by signaling molecules (eg, microRNAs [miRNAs]) contained in extracellular vesicles (EVs) that are released by the placenta into the maternal circulation. We investigated whether maternal exposure to the EDCs phthalates and personal care products alters the miRNA profile of placental-derived EVs circulating in maternal blood. Blood and urine samples from pregnant women with uncomplicated term dichorionic, diamniotic twin pregnancies were analyzed as part of a larger study investigating correlations between exposure of phthalate and personal care products and epigenetic alterations in twin pregnancies. We explored correlations between maternal urinary levels of 13 phthalate and 12 personal care products metabolites and the miRNA profile of placental EVs (EV-miRNAs) circulating in maternal blood. The expression of miR-518e was highest among women with high urinary levels of monobenzyl phthalate and methyl paraben. miR-373-3p was the least expressed in women exposed to high levels of methyl paraben, and miR-543 was significantly downregulated in women exposed to high levels of paraben metabolites, dichlorophenol metabolites, and triclosan. In conclusion, this pilot study reveals that prenatal exposure to EDCs is associated with altered profile of circulating placenta-derived EV-miRNAs. Further studies are needed to generalize these results to singleton pregnancies and to assess whether these alterations are associated with pregnancy complications.

Impacts of bisphenol A (BPA) and phthalate exposures on epigenetic outcomes in the human placenta

“…However, a recent small ( n = 10 twin pregnancies) study assessed 3 circulating placentally sourced miRs (identified a priori in a literature search) in maternal plasma to assess associations with phthalates and phenols. Authors reported that MBzP, but not other phthalates, was positively associated with miR_518e, and that several phenols ( Table 2 ) were positively or negatively associated with the 3 measured miRs [ 93 ]. These data are promising, and should be followed up by analyses in larger cohorts, assessing a wider array of placenta-specific miRs.…”

Phthalate Exposure and Long-Term Epigenomic Consequences: A Review

“…Placenta-derived EV-miRNAs are released by the placenta into the maternal circulation during pregnancy, and are responsible for regulating the endocrine environment to facilitate pregnancy and fetal growth (Mitchell et al, 2015). An exploratory study revealed that maternal exposure to phthalates and parabens can alter the profile of circulating EV-miRNAs (Zhong et al, 2019). miR-518e is highly expressed in women with elevated urinary levels of monobenzyl phthalate and methyl paraben.…”

“…miR-518e is highly expressed in women with elevated urinary levels of monobenzyl phthalate and methyl paraben. miR-373-3p had the lowest expression in women exposed to high levels of methyl paraben while miR-543 showed significant downregulation in women with high levels of paraben metabolites (Zhong et al, 2019). miR-518e, a member of the C19MC family is restricted to the placenta and the reproductive system and has high expression levels in the placentas of women having preeclampsia (Yang et al, 2015;Vashukova et al, 2016).…”

Placental microRNAs: Responders to environmental chemicals and mediators of pathophysiology of the human placenta

“…In another study, blood and urine from women pregnant with uncomplicated, healthy twins were analyzed for the correlation between prenatal phthalate exposure and miRNA profiles in extracellular vesicles (EV-miRNA) in maternal blood [ 88 ]. The researchers evaluated 20 placental-derived EV-miRNAs circulating in maternal plasma in relation to 13 phthalates and eight other chemicals used in plastics.…”

“…The researchers evaluated 20 placental-derived EV-miRNAs circulating in maternal plasma in relation to 13 phthalates and eight other chemicals used in plastics. Only MBzP displayed a positive association with miR-518 [ 88 ]. MBzP is a metabolite formed from butyl benzyl phthalate [ 89 ], and seems to have a potent effect on placental miRNA expression, specifically those implicated in preeclampsia.…”