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

Claudia Gundacker; Klaudia Graf-Rohrmeister; Martin Gencik; Markus Hengstschläger; Karol Holoman; Petra Rosa; Renate Kroismayr; Ivo Offenthaler; Veronika Plichta; Theresa Reischer; Isabella Teufl; Wolfgang Raffesberg; Sigrid Scharf; Birgit Köhler-Vallant; Zoja Delissen; Stefan Weiß; Maria Uhl

doi:10.3389/fgene.2021.664946

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

Front Genet. 2021 Jun 16:12:664946. doi: 10.3389/fgene.2021.664946. eCollection 2021.

Authors

Claudia Gundacker¹, Klaudia Graf-Rohrmeister^{2

3}, Martin Gencik⁴, Markus Hengstschläger¹, Karol Holoman⁵, Petra Rosa⁵, Renate Kroismayr^{6

7}, Ivo Offenthaler⁷, Veronika Plichta^{1

8}, Theresa Reischer¹, Isabella Teufl¹, Wolfgang Raffesberg⁷, Sigrid Scharf⁷, Birgit Köhler-Vallant⁷, Zoja Delissen^{1

4}, Stefan Weiß⁷, Maria Uhl⁷

Affiliations

¹ Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
² Semmelweis Frauenklinik, Vienna, Austria.
³ Klinik Floridsdorf, Vienna, Austria.
⁴ Medgene, Bratislava, Slovakia.
⁵ University Hospital Bratislava-Ružinov, Bratislava, Slovakia.
⁶ Department of Biochemical Engineering, University of Applied Sciences Technikum Wien, Vienna, Austria.
⁷ Environment Agency Austria, Vienna, Austria.
⁸ Austrian Agency for Food and Health Safety, Vienna, Austria.

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.

Keywords: Bisphenol a (BPA); Mercury (Hg); birth outcome; genotype-phenotype; lead (Pb); perfluoroalkyl substances (PFAS); placental transfer.