Association of urinary bisphenol A and phthalate metabolites with markers of oxidative stress in patients with unexplained recurrent spontaneous abortion

Objective To investigate the relationship of the levels of urinary bisphenol A (BPA) and phthalate metabolites (mPAEs) with the levels of oxidative stress markers in patients with unexplained recurrent spontaneous abortion (URSA).

Methods Using the cross-sectional study method, patients with URSA were recruited from Beijing Obstetrics and Gynecology Hospital of Capital Medical University from April to October in 2018. The concentrations of BPA and mPAEs in urine were determined by UPLC-MS, and the concentrations of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α) in urine were determined by enzyme-linked immunosorbent assay. Multiple linear regression model and restricted cubic spline functions were used to evaluate the relationship of BPA and mPAEs levels with 8-OHdG and 8-iso-PGF2α concentrations in urine.

Results A total of 94 participants were included, aged 32.38 ± 3.89 years old. The result of multiple linear regression showed that after adjusting for confounding factors, the concentrations of urinary BPA and mPAEs were significantly positively correlated with urinary 8-OHdG and 8-iso-PGF2α in patients with URSA (all P < 0.05). The result of restricted cubic spline functions analysis showed that urinary 8-OHdG in patients with URSA was a positively linear correlated with BPA (P_{total correlation} = 0.002), a positively nonlinear correlated with urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethylhexyl) phthalate (MEHP) (P_{nonlinear correlation} = 0.046, P_{nonlinear correlation} = 0.046, P_{nonlinear correlation} = 0.007), and had a "U" type relationship with urinary monomethyl phthalate (MMP) (P_{nonlinear correlation} = 0.005). There was a positive linear correlation between Urinary 8-iso-PGF2α and BPA, monoisobutyl phthalate (MiBP), MEHHP, MEOHP and MEHP (P_{total correlation} < 0.05), and a "U" type relationship with urinary MMP (P_{nonlinear correlation} = 0.006).

Conclusion Urinary BPA and mPAE levels were significantly associated with oxidative stress biomarkers in patients with URSA, but the correlation curves were different for different metabolites.