Perfluoroalkyl and polyfluoroalkyl substances in cord serum of newborns and their potential factors.

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.

Third-hand smoke exposure is associated with abnormal serum melatonin level via hypomethylation of CYP1A2 promoter: Evidence from human and animal studies.

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.

Dichloroacetic acid-induced dysfunction in rat hippocampus and the protective effect of curcumin.

The present study was designed to evaluate the role of cAMP-PKA-CREB signaling in mediating the neuroprotective effects of curcumin against DCAA-induced oxidative stress, inflammation and impaired synaptic plasticity in rats. Sixty Sprague-Dawley rats were randomly divided into five groups, and we assessed the histomorphological, behavioral and biochemical characteristics to investigate the beneficial effects of different concentrations of curcumin against DCAA-induced neurotoxicity in rat hippocampus. The results indicated that animal weight gain and food consumption were not significantly affected by DCAA. However, behavioral tests, including morris water maze and shuttle box, showed varying degrees of alterations. Additionally, we found significant changes in hippocampal neurons by histomorphological observation. DCAA exposure could increase lipid peroxidation, reactive oxygen species (ROS), inflammation factors while reducing superoxide dismutase (SOD) activity and glutathione (GSH) level accompanied by DNA damage in the hippocampus. Furthermore, we found that DCAA exposure could cause a differential modulation of mRNA and proteins (cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP-response element-binding protein (CREB), p-CREB, brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95), synaptophysin (SYP)). Conversely, various doses of curcumin attenuated DCAA-induced oxidative stress, inflammation response and impaired synaptic plasticity, while elevating cAMP, PKA, p-CREB, BDNF, PSD-95, SYP levels. Thus, curcumin could activate the cAMP-PKA-CREB signaling pathway, conferring neuroprotection against DCAA-induced neurotoxicity.

Fetal exposure to dichloroacetic acid and impaired cognitive function in the adulthood.

INTRODUCTION: Dichloroacetic acid (DCA), a by-product of disinfection in drinking water, is a multiple organ carcinogen in humans and animals. Still, little research on its neurotoxicity and its underlying mechanism has not been elucidated. METHODS: Sprague Dawley rats were intragastrically treated with DCA at 10, 30, 90 mg/kg body weight from pregnancy till delivery. At eight weeks of age of pups, we assessed cognitive performance using the standard behavioral tests. And the hippocampus structure and ultrastructure were evaluated using light and electron microscope. The oxidative stress indicators and neuroinflammation factors were measured with the corresponding kits. The mRNA and protein of synaptic factors were detected using RT-PCR and Western blot. RESULTS: The results indicated that maternal weight gain and offspring birthweight were not significantly affected by DCA. However, behavioral tests, including morris water maze and step down, showed varying degrees of changes in DCA-treated pups. Additionally, we found significant differences in hippocampal neurons by histomorphological observation. Biochemical analysis results indicated superoxide dismutase (SOD) and catalase (CAT) activities, as well as reactive oxygen species (ROS), nitric oxide (NO), and reduced glutathione (GSH) levels, were affected by DCA accompanying with DNA damage. Moreover, the results showed that the neuroinflammation factors (TNF-α, IL-6, IL-1ß) in DCA treatment groups increased significantly compared with the control pups. And we also found that DCA treatment caused a differential modulation of proteins (BDNF, cAMP-response element-binding protein1 (CREB1), p-CREB1, postsynaptic density-95 (PSD-95), synapsin I, p-synapsin I), and mRNA (BDNF, PSD-95). CONCLUSIONS: Taken together, these results above showed that oxidative stress, neuroinflammation response, and weakened synaptic plasticity in pups hippocampus induced by fetal exposure to DCA could damage the function of memory and cognition in the adulthood.

Prenatal famine exposure and estimated glomerular filtration rate across consecutive generations: association and epigenetic mediation in a population-based cohort study in Suihua China.

Prenatal malnutrition could promote renal dysfunction in adulthood, but it is unclear whether the detrimental effect could be transmitted to the next generation. We investigated whether famine exposure was associated with variation of estimated glomerular filtration rate(eGFR) in two generations and explored the mediation role of methylation alterations. The longitudinal analysis included 2909 participants from Suihua rural area. F1 and F2 generations were divided into non-famine and famine group based on their birth year and exposure status of their parents, respectively. The eGFR was calculated by using the chronic kidney disease epidemiology collaboration equation. We applied mixed-effect models to investigate the association between famine and ΔeGFR and tested blood DNA methylomes in 46 families across two generations. The mediation-analysis models were utilized to examine the mediation effect of methylation alterations on the famine-ΔeGFR association.In mixed-effect models, famine exposure was associated with declined ΔeGFR level in F1(ß:-8.32;95%CI:-11.51,-5.12) and in F2(ß:-6.11;95%CI:-11.88, -0.43). Methylation850K BeadChip data showed only 19 of 961 F1 differentially methylated sites showed concordant alterations in F2. The mediation-analysis results showed methylation alterations on AGTR1 and PRKCA might mediate the famine-ΔeGFR association. Overall, prenatal famine exposure may have long-term effects on eGFR decline across consecutive generations which might be partly mediated by methylation alterations on AGTR1 and PRKCA.