Toxic effects of microcystin-LR on the development of prostate in mice

摘要

Although it is well known that microcystin-LR (MC-LR) may cause male reproductive toxicity, less is known on its potential impact on the development of prostate. In this study, from the 12th day in the embryonic period to the 21st day after birth, 4 randomly assigned groups of pregnant mice were exposed to 0,1,10, and 50 mu g/L of MC-LR through drinking water followed by the analyses of their 30- and 90-day old male offspring. The result showed that MC-LR could enter and be accumulated in the offsprings prostate. Using serological, morphological, and immunohistochemical analysis, we explored the effect of perinatal MC-LR exposure on the prostate development of male offspring. With increasing MC-LR concentrations, the 30 day-old male offspring experienced decreased prostate index, increased serum testosterone levels, decreased serum estradiol levels, and increased the serum androgen/estrogen ratio. Morphological findings showed a significant acini branching defect in both the10 and 50 mu g/L group and increasing MC-LR exposures induced augmented expression of androgen receptor (AR) and estrogen receptor alpha(ER alpha). For the 90-day group, MC-LR exposure resulted in decreased physiological indexes including prostate index and the serum androgen/estrogen ratio. Pathological changes could be observed in prostate tissues of mice treated with MC-LR. Increased expression of AR and ER alpha was also observed. Taken together, our results demonstrated that perinatal MC-LR exposure interfered with the development of the prostate in the offspring, evidenced by prostatic necrosis, hyperplasia, inflammation, and fibrosis, anddisordered hormone conversion of androgen to estrogen inducing imbalance of androgen and estrogen in the prostate may be one of the potential mechanisms of MC-LR disrupting prostate development.