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Updated: Jul 16, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Effects of sub-chronic exposure to microcystin-LR on the endocrine system of male rats
Yu-Ting Wang1, Qian-Hui Wu1, Liang Chen2
1Collaborative 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.
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.
Insights
Microcystin-LR (MC-LR) exposure in rats disrupts hormone levels and damages endocrine glands. This study reveals MC-LR causes endocrine disruption via the hypothalamic-pituitary-adrenal, -gonad, and -thyroid axes.
Area of Science:
- Environmental Toxicology
- Endocrinology
- Mammalian Physiology
Background:
- Microcystins (MCs) are potent toxins known to cause reproductive and developmental toxicity.
- Endocrine homeostasis disruption is a significant concern associated with MC exposure in mammals.
Purpose of the Study:
- To investigate the effects of sub-chronic microcystin-LR (MC-LR) administration on the hypothalamic-pituitary-adrenal (HPA), -gonad (HPG), and -thyroid (HPT) axes in male Sprague-Dawley rats.
- To elucidate the mechanisms underlying MC-LR-induced endocrine disruption.
Main Methods:
- Male Sprague-Dawley rats were administered 3 or 30 μg MC-LR/kg body mass daily via intraperitoneal injection for 6 weeks.
- Histological examination, hormone concentration analysis, and assessment of gene/protein expression were performed on hypothalamus, pituitary, adrenal, testes, and thyroid tissues.
- Evaluated effects on HPA, HPG, and HPT axes, including key hormone levels and feedback regulation.
Main Results:
- MC-LR exposure caused histological damage to endocrine glands and altered organ masses.
- The HPA axis was activated, with significantly increased concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT).
- HPG axis alterations included decreased gonadotropin-releasing hormone (GnRH) and dihydrotestosterone (DHT), with increased luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and estradiol (E2). Free tetra-iodothyronine (fT4) decreased, while other HPT axis hormones remained unchanged.
- Steroid hormone synthesis-related genes and proteins were significantly altered, suggesting disrupted synthesis and secretion pathways.
Conclusions:
- MC-LR acts as an endocrine disruptor by interfering with hormone synthesis and secretion along the HPA, HPG, and HPT axes.
- Evidence suggests potential crosstalk and disrupted negative feedback regulation among these endocrine axes.
- These findings provide mechanistic insights into the endocrine-disrupting effects of microcystins.
