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This study aimed to examine whether and how third-hand smoke (THS) exposure would influence serum melatonin level. 1083 participants with or without exposure to THS were enrolled. Serum ROS, SOD, GSH-Px, and melatonin were measured by ELISA. Methylation microarrays detection and WGCNA were performed to identify hub methylated-sites. The methylation levels of hub-sites were validated in addtional samples. Moreover, mice were exposed to THS for 6 months mimicking exposure of human and the serum, liver, and pineal were collected. Oxidative stress-related indicators in serum, pineal, and liver were measured by ELISA. The expressions of mRNA and protein and methylation levels of hub-gene discovered in human data were further explored by RT-PCR, western-blot, and TBS. The results showed the participants exposed to THS had lower melatonin-level. 820 differentially methylated sites associated with THS were identified. And the hub-site located on the CYP1A2 promoter was identified, which mediated the association between THS and decreased melatonin-level. Decreased peak of serum melatonin, increased ROS and reduced SOD and GSH-Px in pineal and liver, and elevated CYP1A2 expression in liver was also found in the THS-exposed mice. Hypo-methylation of 7 CPG sites on the CYP1A2 promoter was identified, which accelerated the catabolism of melatonin. Overall, THS exposure is associated with abnormal melatonin catabolism through hypo-methylation of CYP1A2-promoter. [Display omitted] • We firstly found the association between third-hand smoke and abnormal serum melatonin. • We innovatively combine epigenetics with third-hand smoke for differential methylation sites. • We firstly identified the hub gene CYP1A2, and animal models were used to study the potential mechanism. We innovatively found that THS-exposure is associated with abnormal serum melatonin levels via hypo-methylation of CYP1A2 promoter in cross-sectional and animal studies. [ABSTRACT FROM AUTHOR]

The demonstrated developmental and reproductive toxicity of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), coupled with the increasing production and use of emerging per- and polyfluoroalkyl substances (PFASs) has resulted in progressively higher human exposure levels. This has raised concerns about PFAS exposure levels in the fetus, which is highly susceptible to the potential effects of hazardous environmental chemicals. However, in utero exposure to PFASs and health implications have not been fully characterized in China. To fill this gap, we analyzed 19 PFASs in umbilical cord serum samples (n = 66). Information about the mothers and newborns was obtained through questionnaires. Associations between maternal characteristics and neonatal birth weight and PFAS concentrations were analyzed using nonparametric tests. As results, PFOA was detected in all serum samples. The highest median concentration of PFOS in umbilical serum was 1.092 ng·mL-1, followed by perfluoropentanoic acid (median: 0.633 ng·mL-1). Trifluroacetic acid and perfluoropropanoic acid were detected in cord serum for the first time, and their median concentrations were 0.229 and 0.266 ng·mL-1, respectively. Neonatal birth weight was negatively correlated with long-chain PFOS (r = −0.319, P < 0.05), and the concentrations of perfluoroundecanoic acid and perfluorododecanoic acid were significantly different between the birth weight groups. Maternal age, maternal education, diet, and nutritional supplementation during pregnancy can all affect umbilical serum exposure to PFASs. These results demonstrate that legacy PFASs remain major contributors to the composition of human PFASs, while the concentration levels of emerging short-chain alternatives have increased significantly. Modifying the mother's diet may reduce the risk of intrauterine PFAS exposure. Special attention to exposure to highly novel PFASs and confirmation of potential determinants should be taken as a priority in the plan for risk management and actions in this area. [Display omitted] • Establishment of UPLC-MS/MS for the detection of target compounds ranging from 2 to 18 carbons. • TFA and PFPrA concentrations in human cord serum are reported for the first time. • The levels of emerging short-chain alternatives have increased significantly. • Nutritional supplements and diet during pregnancy may affect PFAS exposure differently. [ABSTRACT FROM AUTHOR]