Zhang Hui, Wang Lihui, Shen Song, Wang Chenchen, Xiang Zou, Han Xiaodong, Li Dongmei
Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
Toxicology. 2017 Apr 1;380:50-61. doi: 10.1016/j.tox.2017.02.004. Epub 2017 Feb 8.
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 50μg/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 50μg/L group and increasing MC-LR exposures induced augmented expression of androgen receptor (AR) and estrogen receptor α (ERα). 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 ERα 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.
虽然众所周知微囊藻毒素-LR（MC-LR）可能会导致雄性生殖毒性，但对于其对前列腺发育的潜在影响却知之甚少。在本研究中，从胚胎期第12天到出生后第21天，将4组随机分配的怀孕小鼠通过饮用水分别暴露于0、1、10和50μg/L的MC-LR，随后对其30日龄和90日龄的雄性后代进行分析。结果表明，MC-LR能够进入并蓄积在后代的前列腺中。我们采用血清学、形态学和免疫组化分析方法，探讨了围产期暴露于MC-LR对雄性后代前列腺发育的影响。随着MC-LR浓度的增加，30日龄雄性后代的前列腺指数降低、血清睾酮水平升高、血清雌二醇水平降低以及血清雄激素/雌激素比值升高。形态学结果显示，在10μg/L和50μg/L组中均存在明显的腺泡分支缺陷，且MC-LR暴露增加会诱导雄激素受体（AR）和雌激素受体α（ERα）表达增强。对于90日龄组，MC-LR暴露导致包括前列腺指数和血清雄激素/雌激素比值在内的生理指标降低。在MC-LR处理的小鼠前列腺组织中可观察到病理变化，同时也观察到AR和ERα表达增加。综上所述，我们的结果表明，围产期暴露于MC-LR会干扰后代前列腺的发育，表现为前列腺坏死、增生、炎症和纤维化，雄激素向雌激素的激素转化紊乱导致前列腺中雄激素和雌激素失衡可能是MC-LR破坏前列腺发育的潜在机制之一。
