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.
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.
Sci Total Environ. 2024 Jan 1;906:166839. doi: 10.1016/j.scitotenv.2023.166839. Epub 2023 Sep 9.
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.
微囊藻毒素 (MCs) 可引起哺乳动物的生殖和发育毒性，并破坏其内分泌稳态。在本研究中，雄性 Sprague-Dawley (SD) 大鼠通过腹腔内 (i.p.) 注射每天接受 3 或 30μg MC-LR/kg 体重，共 6 周。评估了 MC-LR 对下丘脑-垂体-肾上腺 (HPA)、-性腺 (HPG) 和 -甲状腺 (HPT) 轴沿线的组织学、激素浓度、基因转录谱和蛋白质表达的影响。亚慢性 MC-LR 给药导致下丘脑、垂体、肾上腺、睾丸和甲状腺的组织学损伤，并影响垂体、肾上腺和睾丸的相对质量。HPA 轴被激活，促肾上腺皮质激素释放激素 (CRH)、促肾上腺皮质激素 (ACTH) 和皮质酮 (CORT) 的血清浓度显著增加。沿着 HPG 轴，促性腺激素释放激素 (GnRH) 和二氢睾酮 (DHT) 的血清浓度降低，而黄体生成素 (LH)、卵泡刺激素 (FSH)、睾酮 (T) 和雌二醇 (E2) 的浓度增加。对于 HPT 轴，只有游离四碘甲状腺原氨酸 (fT4) 的浓度显著降低，而促甲状腺素释放激素 (TRH)、促甲状腺激素 (TSH) 或游离三碘甲状腺原氨酸 (fT3) 的浓度没有显著变化。此外，与合成类固醇激素相关的几个基因和蛋白质也发生了显著改变。本研究的结果表明，MC-LR 可以通过干扰 HPA、HPG 和 HPT 轴沿线激素的合成和分泌以及负反馈调节来引起内分泌干扰作用。此外，HPA、HPG 和 HPT 轴之间可能存在串扰。这些发现阐明了 MCs 引起内分泌干扰作用的机制。
