title: MC-LR Exposure Leads to Subfertility of Female Mice and Induces Oxidative Stress in Granulosa Cells.
abstract: Health risk of human exposure to microcystin-leucine arginine (MC-LR) has aroused more and more attention over the past few decades. In the present study, MC-LR was orally administered to female mice at 0, 1, 10 and 40 μg/L for three and six months. We found that chronic exposure to MC-LR at environmental levels could stimulate follicle atresia and lead to decreased developmental follicles, accompanied by a reduction of gonadosomatic index (GSI). In line with the irregular gonadal hormone level and estrus cycles, subfertility of female mice was also confirmed by analyzing numbers of litters and pups. The in vitro study suggested that granulosa cells could uptake MC-LR and should be the target of the toxicant. Oxidative stress in granulose cells induced by MC-LR promoted follicle atresia and eventually leads to female subfertility.
authors.affiliation: Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu, China. wujiang@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu, China. wujiang@nju.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu, China. ymmslim@outlook.com.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu, China. ymmslim@outlook.com.
authors.forename: Mingming
authors.initials: M
authors.lastname: Yuan
authors.affiliation: Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu, China. b101230061@smail.nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu, China. b101230061@smail.nju.edu.cn.
authors.forename: Yuefeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu, China. medsunfeng@smail.nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu, China. medsunfeng@smail.nju.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Sun
authors.affiliation: Immunology and Reproduction Biology Laboratory and State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing 210093, Jiangsu, China. hanxd@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, Jiangsu, China. hanxd@nju.edu.cn.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004958:Estradiol / Q000097:blood; D005260:Female; D005496:Follicular Atresia; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D007246:Infertility / Q000139:chemically induced*; D008297:Male; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D011374:Progesterone; D004958:Estradiol; D002374:Catalase; D013482:Superoxide Dismutase; C057862:cyanoginosin LR
keywords: MC-LR; female subfertility; follicle atresia; granulosa cells; oxidative stress