Effects of sub-chronic exposure to microcystin-LR on the endocrine system of male rats

Yu-Ting Wang; Qian-Hui Wu; Liang Chen; John P Giesy; Lin-Lin Xu; Wen-Li Xu; Jun He; Ting Shi; Yi-Qing Liu; Shi-Man Xiao; Ye-Ke Wang; Feng Chen; Yang Chen; Ning-Hui Xu; Ya-Li Ge; Ling Chu; Yun-Zhi Yan; Jun Chen; Ping Xie

doi:10.1016/j.scitotenv.2023.166839

Effects of sub-chronic exposure to microcystin-LR on the endocrine system of male rats

Sci Total Environ. 2024 Jan 1:906:166839. doi: 10.1016/j.scitotenv.2023.166839. Epub 2023 Sep 9.

Authors

Yu-Ting Wang¹, Qian-Hui Wu¹, Liang Chen², John P Giesy³, Lin-Lin Xu⁴, Wen-Li Xu⁴, Jun He⁴, Ting Shi⁴, Yi-Qing Liu⁵, Shi-Man Xiao⁵, Ye-Ke Wang⁴, Feng Chen⁴, Yang Chen⁴, Ning-Hui Xu¹, Ya-Li Ge⁶, Ling Chu⁶, Yun-Zhi Yan⁷, Jun Chen⁸, Ping Xie²

Affiliations

¹ Collaborative Innovation Center of Recovery and Reconstruction of Degraded Ecosystem in Wanjiang Basin Co-founded by Anhui Province and Ministry of Education, School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China; Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
² Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China; Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650500, China.
³ Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5B3, Canada; Department of Integrative Biology and Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane Road, East Lansing, MI, USA; Department of Environmental Sciences, Baylor University, Waco, TX 76706, USA.
⁴ Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ Institute for Ecological Research and Pollution Control of Plateau Lakes, School of Ecology and Environmental Science, Yunnan University, Kunming 650500, China.
⁶ Collaborative Innovation Center of Recovery and Reconstruction of Degraded Ecosystem in Wanjiang Basin Co-founded by Anhui Province and Ministry of Education, School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China.
⁷ Collaborative Innovation Center of Recovery and Reconstruction of Degraded Ecosystem in Wanjiang Basin Co-founded by Anhui Province and Ministry of Education, School of Ecology and Environment, Anhui Normal University, Wuhu 241002, China. Electronic address: yanyunzhi@ahnu.edu.cn.
⁸ Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: chenjun@ihb.ac.cn.

PMID: 37690761
DOI: 10.1016/j.scitotenv.2023.166839

Abstract

Microcystins (MCs) can cause reproductive and developmental toxicity and disrupt endocrine homeostasis in mammals. In the present study, male, Sprague-Dawley (SD) rats were administrated 3 or 30 μg MC-LR/kg, body mass (bm) per day via intraperitoneal (i.p.) injections for 6 weeks. Effects of MC-LR on histology, hormone concentrations, gene transcriptional profiles and protein expressions along the hypothalamic-pituitary-adrenal (HPA), -gonad (HPG) and -thyroid (HPT) axes were assessed. Sub-chronic administration with MC-LR caused histological damage to hypothalamus, pituitary, adrenal, testes and thyroid and affected relative masses of pituitary, adrenal and testes. The HPA axis was activated and serum concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were significantly augmented. Along the HPG axis, serum concentrations of gonadotropin-releasing hormone (GnRH) and dihydrotestosterone (DHT) were diminished, while concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and estradiol (E2) were augmented. For the HPT axis, only concentrations of free tetra-iodothyronine (fT4) were significantly diminished, while concentrations of thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH) or free tri-iodothyronine (fT3) were not significantly changed. Also, several genes and proteins related to synthesis of steroid hormones were significantly altered. Findings of the present study illustrate that MC-LR can cause endocrine-disrupting effects through the disruption of synthesis and secretion of hormones along the HPA, HPG and HPT axes and negative feedback regulation. Also, there could be crosstalk among HPA, HPG and HPT axes. These findings elucidate mechanisms of endocrine-disrupting effects of MCs.

Keywords: Cyanobacteria; Endocrine-disrupting effects; Gene transcription; Hormones; Protein expression.

MeSH terms

Animals
Endocrine System
Hypothalamo-Hypophyseal System*
Male
Mammals / metabolism
Microcystins* / toxicity
Pituitary-Adrenal System / metabolism
Rats
Rats, Sprague-Dawley
Testosterone

Substances

cyanoginosin LR
Microcystins
Testosterone