Inverse association of certain seminal phthalate metabolites with semen quality may be mediated by androgen synthesis: A cross-sectional study from the South China.

BACKGROUND Several in vitro and in vivo studies have demonstrated the effects of phthalates on androgen synthesis, and the adverse outcomes of phthalate exposure on male reproductive function have been reported. However, the direct relationship among these three factors remains unknown. OBJECTIVE To explore the potential roles of steroids involved in androgen synthesis in the association between phthalate exposure and semen quality. METHODS Eighteen phthalate metabolites (mPAEs) and nine steroids were analyzed in semen samples of 403 male participants aged 18-54 years from a hospital in Shenzhen, China. The associations across phthalate metabolites, steroids, and eleven semen quality parameters were evaluated by multivariate linear regression and logistical regression models. The potential contributions of steroids to the associations between phthalate metabolites and semen quality outcomes were explored by mediation effect analysis. RESULTS In this cross-sectional study, mono-n-butyl phthalate (MnBP) was inversely associated with nine continuous semen quality parameters in a dose-dependent manner (all p for trend < 0.05). Positive associations were observed between MnBP tertiles and androstenedione (ADD) and pregnenolone (PGL), of which only ADD was significantly associated with sperm quality (i.e., motility, p < 0.05). The estimated average mediated effects of seminal ADD on the associations between MnBP and lower sperm motility parameters (i.e., total motility, TR; progressive motility, PR; curvi-linear velocity, VCL) were 6.4-11.9% (all p < 0.05). The potential mediated effects of ADD on the increasing risks of TR (9.8%) and PR (8.5%) abnormalities induced by MnBP exposure were also observed in logistical regression analysis. CONCLUSION Our results indicated that androgen synthesis in reproductive system may be potentially affected by phthalate exposure, thereby resulting in reduced sperm motility in adult men. Further studies are needed to understand the actual roles and underlying mechanism of action of androstenedione on these associations.