Mediation Effects of Placental Inflammatory Transcriptional Biomarkers on the Sex-Dependent Associations between Maternal Phthalate Exposure and Infant Allergic Rhinitis: A Population-Based Cohort Study

Objective Prenatal phthalate exposure has been associated with placental inflammatory factors and infant allergic rhinitis(AR).However,the results are inconclusive.We designed a population-based cohort study to examine the effects of placental inflammatory biomarkers on the sex-dependent associations between maternal phthalate exposure and infant AR.Methods A total of 2,348 pregnant women from Ma’anshan,Anhui Province,China,who were screened before antenatal visits and met the inclusion criteria,were included in the present study.We assessed AR in their offspring aged 36 months with a questionnaire.Quantitative PCR was performed to measure placental inflammatory factor m RNAs.The independent samples t-test and multivariable logistic regression were used to determine the associations between infant AR and maternal phthalates.Results Childhood AR may be related to education and family monthly income(P = 0.01).The phthalate metabolites,mono(2-ethylhexyl) phthalate(MEHP),mono(2-ethyl-5-hydroxyl) phthalate(MEHHP),in pregnant women were associated with a significantly increased risk for infant AR in males[P < 0.05;odds ratio(OR):1.285;95% confidence interval(CI):1.037-1.591,and OR:1.232,95% CI:1.008-1.507,respectively],but not females.Additionally,irritably-increased expression levels of HO-1 and IL-4 were associated with AR in male infants(OR:1.175;95% CI:1.038-1.329 and OR:1.181;95% CI:1.056-1.322,respectively).The association between maternal urinary MEHHP and placental HO-1 was marginally significant according to mediation analysis.Conclusion The associations of maternal MEHHP and MEOHP levels with fetal AR in males were significant.Placental HO-1 was a fractional mediator in the associations between MEHHP and AR.Thus,the placenta should be further investigated as a potential mediator of maternal exposure-induced disease risk in children.

Persistently Upregulated Hippocampal mTOR Signals Mediated by Fecal SCFAs Impair Memory in Male Pups with SMM Exposure in Utero

Objective To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin(SMM) in pregnancy on the neurobehavioral development of male offspring. Methods Pregnant mice were randomly divided into four groups: control‐(normal saline), low‐[10 mg/(kg.day)], middle‐[50 mg/(kg.day)], and high‐dose [200 mg/(kg.day)] groups, which received SMM by gavage daily during gestational days 1‐18. We measured the levels of short‐chain fatty acids(SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mR NA and protein levels of genes involved in the mammalian target of rapamycin(m TOR) pathway in the hippocampus of male pups by RT‐PCR or Western blotting. Results Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day(PND) 22 and 56. Furthermore, the phosphatidylinositol 3‐kinase(PI3 k)/protein kinase B(AKT)/mTOR or mT OR/ribosomal protein S6 kinase 1(S6 K1)/4 EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase(SPR), a potential target of m TOR, was inhibited. Conclusion In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut(SCFA)‐brain axis may contribute to cognitive deficits in male offspring.