Repeated measurements and mixture effects of urinary bisphenols, parabens, polycyclic aromatic hydrocarbons, and other chemicals on biomarkers of oxidative stress in pre- and postpartum women

Abstract

The association between oxidative stress and exposure to bisphenols, parabens, phenols, polycyclic aromatic hydrocarbons (PAH), and volatile organic compounds (VOCs) has been investigated by many in vitro and in vivo studies. However, most of these findings are based on cross-sectional studies, as a result of which the combined effects of these compounds have been rarely analyzed. In this study, our objective was to assess urinary bisphenols, parabens, PAHs, and VOCs, in relation to oxidative stress during pre-and postpartum periods, analyze the association between these chemicals and oxidative stress via repeated measurements using a linear mixed model (LMM), and evaluate the combined effects exerted by these chemicals on oxidative stress using Bayesian Kernel Machine Regression (BKMR). A total 529 urine samples were collected from 242 pregnant women during the 1st and 2nd trimesters, as well as postpartum follow-ups. Three bisphenols, four parabens, benzopheone-3 (BP-3), triclosan (TCS), four PAHs, two VOCs, and 3- phenoxy-benzoic acid (3-PBA) were analyzed. We also measured 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA), which serve as oxidative stress biomarkers in maternal urine samples. During this period, 8-OHdG decreased steadily, whereas MDA increased during pregnancy and decreased after childbirth. LMM indicated that Bisphenol A, Prophyl-paraben, BP-3, and 1-hydroxypyrene (1-OHP) showed a significant association with increased MDA levels. The BKMR models revealed that the mixture effect exerted by these 16 chemicals had changed MDA levels, which indicate oxidative stress, and that both Butyl Paraben (BP) and 1-hydroxypyrene (1-OHP) had contributed to such oxidative stress. Mixtures of each subgroup (bisphenols, parabens, and PAHs) were associated with increased MDA levels. These findings suggest that exposure to some phenols and PAHs during pre- and post-partum stages may cause oxidative stress, and that exposure to these chemicals should be minimized during this period.