Associations between isoflavone exposure and reproductive damage in adult males: evidence from human and model system studies

It's controversial whether exposure to Isoflavones, constituents of certain Plants such as soy bean, exerts male reproductive toxicity. This study was designed to investigate whether isoflavone exposure during adulthood could have deleterious impacts on male reproductive health by the cross-sectional study, animal experiments, and in vitro tests. In the cross-sectional study, we observed that urinary Isoflavones were not significantly associated with semen quality including sperm concentrations, sperm count, progressive motility, and total motility, respectively (All P-value for trend>0.05). However, negative associations were found between plasma testosterone and urinary Σisoflavones, genistein, glycitein, and dihydrodaidzein (all P-value for trend <0.05). In the animal experiments, serum and intratesticular testosterone levels were decreased in mice exposed to several dosages of genistein. Genistein administration caused up-regulation of Estrogen Receptor alpha (ERα) and down-regulation of cytochrome P45017A1 (CYP17A1) protein levels in testes of mice. However, genistein treatment during adulthood did not induce appreciable structural damages of reproductive system in mice. In vitro tests, we observed that genistein of different dosages (0.01, 2.5, 10 μM) caused a concentration dependent inhibition of testosterone production by TM3 Leydig cells (half-maximal inhibitory concentration = 3.796 nM, P < 0.05). Elevated protein expression of ERα and decreased mRNA/protein level of CYP17A1 were also observed in genistein-treated cells. Protein level of CYP17A1 and testosterone concentration were significantly restored in the ERα siRNA-transfected cells, compared to cells that treated with genistein alone (P < 0.05). The results demonstrate that exposure to Isoflavones during adulthood may be associated with alterations of reproductive Hormones. Particularly for genistein, which inhibits testosterone biosynthesis through up-regulation of ERα in Leydig cells of mice, might induce the disruption of testosterone production in human. The present study provides novel perspective into potential targets for male reproductive compromise induced by isoflavone exposure.