Metabolomics insights into the prenatal exposure effects of polybrominated diphenyl ethers on neonatal birth outcomes

Yanfeng Wang; Qihua Wang; Lina Zhou; Zhijun Zeng; Chunxia Zhao; Lei You; Xin Lu; Xinyu Liu; Runze Ouyang; Yuting Wang; Xijin Xu; Xiwen Tian; Yufeng Guo; Xia Huo; Guowang Xu

doi:10.1016/j.scitotenv.2022.155601

Metabolomics insights into the prenatal exposure effects of polybrominated diphenyl ethers on neonatal birth outcomes

Sci Total Environ. 2022 Aug 25:836:155601. doi: 10.1016/j.scitotenv.2022.155601. Epub 2022 Apr 30.

Authors

Yanfeng Wang¹, Qihua Wang², Lina Zhou³, Zhijun Zeng⁴, Chunxia Zhao³, Lei You¹, Xin Lu³, Xinyu Liu³, Runze Ouyang¹, Yuting Wang¹, Xijin Xu⁵, Xiwen Tian⁴, Yufeng Guo⁴, Xia Huo⁶, Guowang Xu⁷

Affiliations

¹ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, Guangdong, China; Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, the Netherlands.
³ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China; Liaoning Province Key Laboratory of Metabolomics, Dalian, China.
⁴ Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, Guangdong, China.
⁵ Laboratory of Environmental Medicine and Developmental Toxicology, Shantou University Medical College, Shantou 515041, Guangdong, China; Department of Cell Biology and Genetics, Shantou University Medical College, Shantou 515041, Guangdong, China.
⁶ Laboratory of Environmental Medicine and Developmental Toxicology, Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou 511443, Guangdong, China. Electronic address: xhuo@jnu.edu.cn.
⁷ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China; Liaoning Province Key Laboratory of Metabolomics, Dalian, China. Electronic address: xugw@dicp.ac.cn.

PMID: 35504395
DOI: 10.1016/j.scitotenv.2022.155601

Abstract

Background: Effects of polybrominated diphenyl ethers (PBDEs) on neonatal birth outcomes vary across previous studies, and the related mechanism investigation remains poorly understood, especially at the metabolic level.

Objectives: To evaluate the associations between prenatal PBDEs exposure and neonatal birth outcomes including gestational age, neonatal weight, birth length, head circumference (HC), Apgar score at 1 min (Apgar1) and 5 min, and further reveal the underlying metabolic disorders in a population-based birth cohort study.

Methods: Gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS) based targeted method and GC-MS based untargeted method were respectively conducted to obtain PBDE levels and metabolic profiles of 200 placental tissue samples from a typical e-waste recycling area (Guiyu) and reference area (Haojiang) in China. Spearman correlation and regression analyses were applied to assess the associations between the placental PBDE levels and birth outcomes. Metabolome-wide association studies and the meet-in-the-middle approach were employed to explore disruptions linking PBDE exposures and the corresponding adverse birth outcomes.

Results: Eight out of 27 PBDE congeners were detected in placenta with more than 50% frequency in at least one district and significantly higher in Guiyu than those in Haojiang. The lower HC and Apgar1 had significant associations with PBDE exposures after adjustment for potential confounders. A total of 66, 16 and 14 metabolites were significantly correlated with PBDE exposures, HC and Apgar1, respectively. 4 and 12 PBDE-related metabolites were significantly associated with the risks of decreasing neonatal HC and Apgar1. The disrupted metabolites were mainly involved in the pentose phosphate pathway, ascorbate metabolism, threonine metabolism, butanoate metabolism, lipid metabolism, and arginine biosynthesis.

Conclusions: In this birth cohort, higher placental PBDE levels were significantly associated with the lower HC and Apgar1. The associations might be modified by multiple metabolic disturbances through increasing oxidative stress, mediating neurotoxicity, maternal gut microbiota dysbiosis and vasodilatation regulation.

Keywords: Meet-in-the-middle; Metabolomics; Neonatal birth outcome; Placenta; Polybrominated diphenyl ether.

MeSH terms

Cohort Studies
Female
Gas Chromatography-Mass Spectrometry
Halogenated Diphenyl Ethers* / metabolism
Halogenated Diphenyl Ethers* / toxicity
Humans
Infant, Newborn
Maternal Exposure
Metabolomics
Placenta / metabolism
Pregnancy
Prenatal Exposure Delayed Effects*
Tandem Mass Spectrometry

Substances

Halogenated Diphenyl Ethers