Mediating effect of oxidative stress on metabolites of high-molecular-weight PAHs and unexplained recurrent spontaneous abortion

Objective To investigate the association between the metabolites of high-molecular-weight polycyclic aromatic hydrocarbons (HMW PAHs) and unexplained recurrent spontaneous abortion (URSA) and the mediating effect of oxidative stress biomarkers.

Methods Using the case-control study method, the patients with URSA who attended Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University from April to October 2018 were enrolled as the case group, and normal pregnant women who voluntarily went to the outpatient service of the hospital for artificial abortion were enrolled as the control group. A total of 156 subjects were included, with 81 in the case group and 75 in the control group. The 50 mL random midstream urine samples were collected from all subjects, and gas chromatography-tandem mass spectrometry was used to measure the metabolites of 6 HMW PAHs (3-Hydroxyfluoranthene (3-BF), 1-Hydroxypyrene (1-PYR), 6-Hydroxychrysene (6-CHR), 3-Hydroxychrysene (3-CHR), 3-Hydroxybenzaanthracene (3-BAA), and 3-Hydroxybenzoapyrene (3-BAP)). Enzyme-linked immunosorbent assay was used to measure the concentrations of 2 oxidative stress biomarkers, including 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-iso-PGF2α). The multiple logistic regression model was used to assess the association between the metabolites of HMW PAHs and oxidative stress biomarkers with URSA. The multiple linear regression model was used to analyze the association between the metabolites of HMW PAHs and oxidative stress biomarkers. The mediating effect analysis was used to investigate the mediating effect of oxidative stress biomarkers between the metabolites of HMW PAHs and URSA.

Results The subjects had a mean age of (31.91±4.68)years, a mean body mass index of (22.74±4.19)kg/m², and a mean age of menarche of (13.13±1.32)years, and there were significant differences in the age of menarche and educational level between the case group and the control group. The case group had significantly higher levels of 3-BAA and 8-iso-PGF2α than the control group (P<0.05). Compared with the 3-BAA Q1 group, the 3-BAA Q4 group had an increased risk of URSA with an OR (95%CI) of 4.95(1.11, 10.91), P_trend<0.05. 3-BAA was positively associated with 8-OHdG and 8-iso-PGF2α. Compared with the 3-BAA Q1 group, the 3-BAA Q4 group had changes in 8-OHdG and 8-iso-PGF2α levels (95%CI) of 0.75(0.38, 1.13) and 0.84(0.52, 1.15), respectively. The mediating effect analysis showed that 8-iso-PGF2α partially mediated the association between 3-BAA and URSA, with a mediating effect accounting for 31.8%.

Conclusion This study suggests that 8-iso-PGF2α has a mediating effect in the association between 3-BAA and URSA.