Predictive value and mediating effect analysis of the AHR-ARNT-CYP1A1 axis for missed abortion related to polycyclic aromatic hydrocarbons exposure

This study aimed to determine the predictive value of aryl hydrocarbon receptor (AHR) signaling pathway genes, and to detect the mediating effect of AHR that may mediate the influence of polycyclic aromatic hydrocarbons (PAHs) on missed abortion. The present study was conducted using a 1:2 matched case-control study, a total of 94 cases of women with missed abortion and 188 matched women controls with normal pregnancy but voluntarily abortion were included. The receiver operating characteristic curve (ROC) and the area under the ROC curve (AUC) were used to evaluate the predictive value of AHR signaling pathway genes for missed abortion. The mediating role of AHR within the effect pathway between PAHs exposure and missed abortion was performed using the mediation package of the R language. The results showed that the level of PAH-DNA adducts in the case group (487.61 ± 6.29) pg/ml was higher than that in the control group (446.86 ± 5.95) pg/ml (P < 0.001). There were significant differences in the expression levels of AHR, aryl hydrocarbon receptor nuclear translocator (ARNT), aryl hydrocarbon receptor repressor (AHRR), cytochrome P450 enzymes 1A1 (CYP1A1) and glutathione S-transferase P1 (GSTP1) genes between the case group and the control group (P < 0.01). After adjusting for covariates, high exposure of PAH-DNA adducts levels increased AHR and CYP1A1 expression. The 5-fold cross-validation results revealed that the mean value of the area under the ROC curve (AUC) of AHR-ARNT-CYP1A1 axis was 0.931 (95%CI: 0.858 ~ 0.999), which had good predictive performance in assessing the risk of prevalence of missed abortion. AHR gene might play a partial mediating effect in the association between PAHs exposure and missed abortion, and the percentage of mediating effect was 36.56%.