Gene Variants Determine Placental Transfer of Perfluoroalkyl Substances (PFAS), Mercury (Hg) and Lead (Pb), and Birth Outcome: Findings From the UmMuKi Bratislava-Vienna Study

Abstract

Prenatal exposure to perfluoroalkyl substances (PFAS), bisphenol A (BPA), lead (Pb), total mercury (THg), and methylmercury (MeHg) can affect fetal development. Factors influencing placental transfer rate of these toxins are poorly investigated. Whether prenatal exposure to pollutants has an effect on birth weight is incompletely understood. We therefore aimed (1) to determine placental transfer rates of PFAS, BPA, Pb, THg, and MeHg, (2) to analyze relationships between fetal exposure and birth outcome and (3) to analyze gene variants as mediators of placental transfer rates and birth outcome. Two hundred healthy pregnant women and their newborns participated in the study. BPA, 16 PFAS, THg, MeHg, and Pb were determined using HPLCMS/MS (BPA, PFAS), HPLC-CV-ICPMS (MeHg), CV-AFS (THg), and GF-AAS (Pb). Questionnaires and medical records were used to survey exposure sources and birth outcome. 20 single nucleotide polymorphisms and two deletion polymorphisms were determined by real-time PCR from both maternal and newborn blood. Genotype-phenotype associations were analyzed by categorical regression and logistic regression analysis. Specific gene variants were associated with altered placental transfer of PFAS (ALAD Lys59Asn, ABCG2 Gln141Lys), THg (UGT Tyr85Asp, GSTT1del, ABCC1 rs246221) and Pb (GSTP1 Ala114Val). A certain combination of three gene polymorphisms (ABCC1 rs246221, GCLM rs41303970, HFE His63Asp) was over-represented in newborns small for gestational age. 36% of Austrian and 75% of Slovakian mothers had levels exceeding the HBM guidance value I (2 μg/L) of the German HBM Commission for PFOA. 13% of newborns and 39% of women had Ery-Pb levels above 24 μg/kg, an approximation for the BMDL01 of 12 μg/L set by the European Food Safety Authority (EFSA). Our findings point to the need to minimize perinatal exposures to protect fetal health, especially those genetically predisposed to increased transplacental exposure.

Revisiting Genetic Influence on Mercury Exposure and Intoxication in Humans: A Scoping Review

“…Another important system that may play a role in mercury detoxification involves the ABC transporters, a family of membrane proteins [ 68 ]. Interestingly, the SNPs ABCC1 (rs11075290, rs212093 and rs215088), ABCC2 (rs717620) and ABCB1 (rs10276499, rs1202169 and rs2032582) were associated with the modulation of maternal mercury hair levels [ 37 , 51 ]. However, the exact mechanisms and influence of these SNPs on mercury distribution, particularly during pregnancy, are not totally understood [ 37 , 51 ].…”

“…Interestingly, the SNPs ABCC1 (rs11075290, rs212093 and rs215088), ABCC2 (rs717620) and ABCB1 (rs10276499, rs1202169 and rs2032582) were associated with the modulation of maternal mercury hair levels [ 37 , 51 ]. However, the exact mechanisms and influence of these SNPs on mercury distribution, particularly during pregnancy, are not totally understood [ 37 , 51 ]. For example, the ABCC1 rs246221 C allele was associated with a higher rate of placental mercury transfer [ 37 ] and the SNP rs11075290 of the same gene was correlated with decreased umbilical cord mercury (carriers of the T allele showed lower cord mercury levels) [ 56 ].…”

“…However, the exact mechanisms and influence of these SNPs on mercury distribution, particularly during pregnancy, are not totally understood [ 37 , 51 ]. For example, the ABCC1 rs246221 C allele was associated with a higher rate of placental mercury transfer [ 37 ] and the SNP rs11075290 of the same gene was correlated with decreased umbilical cord mercury (carriers of the T allele showed lower cord mercury levels) [ 56 ]. The latter allele was associated with an increased expression of the ABCC1 gene, which could mean a higher mercury detoxification rate [ 56 ].…”

“…In this study, we found only one study with populations from Africa (Tanzania and Zimbabwe) and only two with populations from Asia (Thailand, Philippines and Indonesia). Only three studies included populations of more than one country: Austria and Slovakia [37], Slovenia and Croatia [38], and the Philippines, Indonesia, Tanzania and Zimbabwe [27]. However, these studies did not analyze the ancestry, which would be highly recommended, especially for the latter study by Kolbinger et al (2019), which included populations from three different continents [27].…”

Predicting Exposure to Perfluorinated Alkyl Substances (PFAS) among US Infants

“…Interference with angiogenesis, and its effect on placental sufficiency, might be a cause of or a contributor to the lower birth weights observed with higher maternal serum concentrations of some PFAS [ 32 ], although effects seem to differ according to infant gender. An additional vulnerability is genetic polymorphisms, which may make the placenta of some women better able to transfer hazardous chemicals to the fetus [ 33 ]. More studies will need to be performed in this area that might explain differences in birthweight or other effects between male and female infants [ 34 ].…”