Interactive effects of nonylphenol and bisphenol A exposure with oxidative stress on fetal reproductive indices

Highlights: • Maternal NP exposure may induce 8-OHdG and 8-NO₂Gua. • Prenatal BPA may induce 8-isoPF_2α. • Concurrent exposure to NP and BPA may enhance 8-OHdG. • In the high 8-isoPF_2α group, NP/BPA is inversely related with the fetal penis length. • The interactions of NP/BPA, oxidative stress and penis length should be considered. Nonylphenol (NP) and/or bisphenol A (BPA) may have reproductive effects. Although the mechanisms of action remain unclear, steroid hormones biosynthesis, hypothalamus pituitary adrenal axis activity, oxidative stress, and crosstalk interaction of NP and BPA mixture and its pathways may play a contributory role. This cross-sectional study examined whether the interactive effects of NP/BPA and oxidative stress biomarkers played a role in reproductive indices (penis length and anogenital distance (AGD)) in 244 mother-fetus pairs. Four biomarkers of oxidative stress, (8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO₂Gua), 8-iso-prostaglandin F_2α (8-isoPF_2α), and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were simultaneously analyzed using the high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method. No significant associations were found between reproductive indices and NP/BPA or oxidative stress biomarkers. Maternal exposure to a mixture of NP and BPA may enhance 8-OHdG. Interactive effects were found in the high 8-isoPF_2α group, and prenatal NP exposure was inversely associated with penis length (β = −3.68 mm; p = 0.01). Similar results were noted among boys who were born to mothers in the high 8-isoPF_2α group, in which BPA was inversely associated with penis length (β = −4.43 mm; p = 0.005). Our findings suggest important implications for prenatal exposure to oxidative stress, as evidenced by the 8-isoPF2α level. Thus, NP and BPA may interact to shape fetal reproductive tract development, particularly in boys. The interactive effects of NP/BPA, oxidative stress, and reproductive indices should be considered.