Gestational Exposure to Plastic Additives and Associations with Placental Function-Related Genes

Abstract

Despite an increasing number of environmental reports on plastic additives, gestational exposure to these chemicals has been poorly characterized. The present work aimed to characterize gestational exposure to a total of 50 broadly used plasticizers and antioxidants in women with fullterm (n = 155) and preterm deliveries (n = 75) and to explore the associations of prenatal exposure with the expressions of placental functionrelated genes. A few of them exhibited significantly different concentrations between the preterm and full-term deliveries group, including 2,6-di-tertbutyl-4-(dimethylamino-methyl)phenol (AO4703), dibutyl fumarate (DBF), tributyl citrate (TBC), triethyl citrate (TEC) 2,4-di-tert-butyl-phenol (2,4-DtBP), 2,4-(1,1,3,3-tetra-methylbutyl)phenol (4-tOP), 2,6-di-tert-butyl-4hydroxytoluene (BHT), and their transformation products. Significant associations were determined between the concentrations of selected chemicals among the 14 substances with detection frequency greater than 60% and the mRNA expression levels of selected genes related to placental functions. The associations also exhibited chemical-specific patterns and significantly differed between preterm and full-term deliveries. Our work represents the first population-based study to assess potential links between gestational exposure to selected plasticizers and antioxidants and placental functions, calling for further efforts to elucidate the potential mechanisms and subsequent impacts on adverse pregnancy outcomes.

Target Exposome for Characterizing Early Gestational Exposure to Contaminants of Emerging Concern and Association with Gestational Diabetes Mellitus

“…The LLE-based methodologies generally work for both plasma and serum analysis. , For example, Jamnik et al developed an LC-MS assay to determine >80 highly diverse xenobiotics in various human fluids, in which the same LLE-based sample preparation method was employed for plasma and serum . Furthermore, our protocol has already been validated to be applicable for the analysis of OPEs, PAE metabolites, and synthetic antioxidants in serum. , Therefore, we infer that our protocol would be equally applicable for both plasma and serum. Overall, the above-mentioned advantages, along with satisfactory analytical accuracy, precision, and sensitivity, enable our target exposome protocol a promising approach with great potentials for large-scale biomonitoring and epidemiological studies.…”

“…29 Furthermore, our protocol has already been validated to be applicable for the analysis of OPEs, PAE metabolites, and synthetic antioxidants in serum. 34,35 Therefore, we infer that our protocol would be equally applicable for both plasma and serum. Overall, the above-mentioned advantages, along with satisfactory analytical accuracy, precision, and sensitivity, enable our target exposome protocol a promising approach with great potentials for large-scale biomonitoring and epidemiological studies.…”

Occurrence of Polymer Additives 1,3-Diphenylguanidine (DPG), N-(1,3-Dimethylbutyl)-N′-phenyl-1,4-benzenediamine (6PPD), and Chlorinated Byproducts in Drinking Water: Contribution from Plumbing Polymer Materials

“…8,13,14 DPG has been found to occur in human urine with a detection frequency of 73% in children, 15 while N-(1,3-dimethylbutyl)-N′-phenyl-1,4-benzenediamine (6PPD) has also been found to occur in different human samples. 16,17 While some studies that have highlighted the occurrence in wastewater and drinking water systems of compounds like DPG and 6PPD implicate tire wear related sources, 8,18,19 their diverse usage might suggest that others sources play a critical and little studied role in their occurrence in drinking water. 20 The transformation of such compounds in the environment and engineered systems has also been shown to play a major role in toxicity.…”

“…The occurrence of polymer additives in the environment from surface runoff has been recently associated with serious effects for fish populations, , and while many emerging contaminants are usually found at low nanogram per liter quantities in the environment, numerous recent reports have indicated that polymer additives can occur at much higher concentrations in the microgram per liter range. − 1,3-Diphenylguanidine (DPG) has been shown to be a compound having among the highest detected concentrations in different studies of urban runoff waters. , However, DPG occurrence is not restricted to the aquatic environment but has also been reported in urban air, indoor household dust, and drinking water samples. ,, DPG has been found to occur in human urine with a detection frequency of 73% in children, while N -(1,3-dimethylbutyl)- N ′-phenyl-1,4-benzenediamine (6PPD) has also been found to occur in different human samples. , While some studies that have highlighted the occurrence in wastewater and drinking water systems of compounds like DPG and 6PPD implicate tire wear related sources, ,, their diverse usage might suggest that others sources play a critical and little studied role in their occurrence in drinking water . The transformation of such compounds in the environment and engineered systems has also been shown to play a major role in toxicity. , Indeed, we have previously demonstrated that selected chlorinated products of DPG show greater toxicity than the original parent compound while also being potentially genotoxic .…”