title: Reproduction impairment and endocrine disruption in female zebrafish after long-term exposure to MC-LR: A life cycle assessment.
abstract: Microcystin-LR (MC-LR) has been found to cause reproductive and developmental impairments as well as to disrupt sex hormone homeostasis of fish during acute and sub-chronic toxic experiments. However, fish in natural environments are continuously exposed to MC-LR throughout their entire life cycle as opposed to short-term exposure. Here, we tested the hypothesis that the mechanism by which MC-LR harms female fish reproduction and development within natural water bodies is through interference of the reproductive endocrine system. In the present study, zebrafish hatchlings (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30 μg/L MC-LR for 90 d until reaching sexual maturity. Female zebrafish were selected, and the changes in growth and developmental indicators, ovarian ultrastructure as well as the levels of gonadal steroid hormones and vitellogenin (VTG) were examined along with the transcription of related genes in the hypothalamic-pituitary-gonadal-liver axis (HPGL-axis). The results showed for the first time, a life cycle exposure to MC-LR caused growth inhibition, decreased ovary weight and ovarian ultra-pathological lesions. Decreased ovarian testosterone levels indicated that MC-LR disrupted sex steroid hormone balance. Significantly up-regulated transcription of brain FSHβ and LHβ along with ovarian ERα, FSHR and LHR suggested positive feedback regulation in the HPGL-axis was induced as a compensatory mechanism for MC-LR damage. It was also noted that ovarian VTG content and hepatic ERα and VTG1 expression were all down-regulated, which might be responsible for reduced vitellus storage noted in our histological observations. Our findings indicate that a life cycle exposure to MC-LR impairs the development and reproduction of female zebrafish by disrupting the transcription of related HPGL-axis genes, suggesting that MC-LR has potential adverse effects on fish reproduction and thus population dynamics in MCs-contaminated aquatic environment.
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China. Electronic address: foreverlili78@mail.hzau.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Su
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Wang
authors.initials: W
authors.lastname: Lin
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan 430070, PR China; Key Laboratory of Freshwater Animal Breeding, Ministry of Agriculture, Wuhan 430070, PR China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan 430070, PR China.
authors.forename: Zemao
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008387:Marine Toxins; D052998:Microcystins; D012098:Reproduction / Q000187:drug effects*; D036401:Toxicity Tests, Chronic; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D052244:Endocrine Disruptors; D012739:Gonadal Steroid Hormones; D008387:Marine Toxins; D052998:Microcystins; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; C057862:cyanoginosin LR
keywords: Endocrine-disrupting effect; Hypothalamic–pituitary–gonadal–liver axis; Microcystin-LR; Reproductive toxicity; Sex steroid hormone