A study on the mediating role of serum hormones in the effects of heavy metals on preeclampsia.

Exposure to environmental heavy metals may pose a risk factor for developing preeclampsia (PE) modified through intervention. This case-control study aimed to investigate the association between serum heavy metal concentrations and PE in pregnant women and whether hormones served as mediating factors in the impact of heavy metals on PE. From October 2020 to 2022, 160 patients with PE and 160 pregnant women with normal deliveries were recruited at Dongguan Songshan Lake Central Hospital. Serum concentrations of manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), lead (Pb), ß-human chorionic gonadotropin (ß-hCG), progesterone (P), estradiol (E2), testosterone (T), cortisol (Cort), and cortisone (Cor) were measured. Logistic, restricted cubic splines, weighted quantile sum and multivariate linear regression models were employed to account for different aspects and explore the relationships among heavy metals, hormones, and PE. Mediation model analysis was performed to assess the role of hormones in mediation. The median concentrations of Mn, E2, and Cort were lower in the PE group than in the control group. The median concentrations of Cu, Zn, ß-hCG, and T were higher in the PE than in the control. Mn, E2, and Cort showed negative associations with PE, while Cu, Zn, ß-hCG, and T demonstrated positive associations, as determined through logistic regression. Mn, Cu, and Zn displayed linear dose-response relationships with PE. Zn and Cu had high weights in the positive association model of mixed heavy metal exposure with PE. The mediation analysis revealed that serum E2, P, T, Cort, and Cort/Cor might be potential mediators of the association between heavy metals (Mn, Cu, and Zn) and PE.

The mediating role of steroid hormones in the relationship between bisphenol A and its alternatives bisphenol S and F exposure and preeclampsia.

Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17 % of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion, maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE.

Estimation of urinary cadmium benchmark dose thresholds for preschool children in a cadmium-polluted area based on Bayesian model averaging.

Urinary cadmium (U-Cd) values are indicators for determining chronic cadmium toxicity, and previous studies have calculated U-Cd indicators using renal injury biomarkers. However, most of these studies have been conducted in adult populations, and there is a lack of research on U-Cd thresholds in preschool children. We aimed to apply benchmark dose (BMD) analysis to estimate the U-Cd threshold level associated with renal impairment in preschool children in the cadmium-polluted area. 518 preschool children aged 3-5 years were selected by systematic sampling (275 boys, 243 girls). Urinary cadmium and three biomarkers of early renal injury (urinary N-acetyl-ß-D-glucosaminidase, UNAG; urinary ß2-microglobulin, Uß2-MG; urinary retinol-binding protein, URBP) were determined. Bayesian model averaging estimated the BMD and lower confidence interval limit (BMDL) of U-Cd. The medians U-Cd levels in both boys and girls exceeded the recommended national standard threshold (5 µg/g cr) and U-Cd levels were higher in girls than in boys. Urinary N-acetyl-ß-D-glucosaminidase (UNAG) was the most sensitive biomarker of renal effects in preschool children. The overall BMDL5 (BMDL at a benchmark response value of 5) was 2.76 µg/g cr. In the gender analysis, the BMDL5 values were 1.92 µg/g cr for boys and 4.12 µg/g cr for girls. This study shows that the U-Cd threshold (BMDL5) is lower than the national standard (5 µg/g cr) and boys' BMDL5 was lower than the limit set by the European Parliament and Council in 2019 (2 µg/g cr), which provides a reference point for making U-Cd thresholds for preschool children.