title: Toxic effects of microcystin-LR on the development of prostate in mice.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Lihui
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Song
authors.initials: S
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: 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. Electronic address: hanxd@nju.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
authors.affiliation: 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. Electronic address: lidm@nju.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
mesh_terms: D000728:Androgens / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008387:Marine Toxins; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000633:toxicity*; D011467:Prostate / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D000728:Androgens; D004958:Estradiol; D004967:Estrogens; D015850:Interleukin-6; D008387:Marine Toxins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D052998:Microcystins; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D013739:Testosterone; D014409:Tumor Necrosis Factor-alpha; D000097983:ERRalpha Estrogen-Related Receptor; C000607144:AR protein, mouse; C577686:interleukin-6, mouse; C522362:Mmp2 protein, mouse; C501830:Mmp9 protein, mouse; C057862:cyanoginosin LR
keywords: Microcystin-LR (MC-LR); Perinatal exposure; Prostate development; Reproductive toxicity