(P-131) Single Microcystin Exposure Impairs the Hypothalamic-Pituitary-Gonadal Axis at Different Levels in Female Rats

Abstract Authors: Flavia C. F. Dos Santos¹, Gabriela F. C. Lima¹, Eduardo Merlo¹, Cidalia de F. Januario¹, Leandro Miranda-Alves², Rosiane A. Miranda³; Patrícia C. Lisboa³, Jones B. Graceli¹.

¹Department of Morphology, Federal University of Espírito Santo, 290440-090, Vitória, Brazil.

²Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 21941-904, Ilha do Governador, Brazil

³Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, RJ, Brazil.

Abstract Text: Microcystin (MC) is the most common cyanobacterial toxin. Few studies have evaluated the MC effects on the hypothalamic-pituitary-gonadal (HPG) axis function. In this study, we assessed whether MC exposure results in HPG axis changes. Female rats were exposed to a single dose of MC at environmentally relevant levels 5, 20 and 40 μg/kg (MC5, 20 and 40 respectively, n=15). After 24 hours, we evaluated reproductive parameters for 15 days. Improper functioning of the HPG axis was observed in MC rats. Specifically, MC reduced hypothalamic gonadotropin-releasing hormone (GnRH) protein expression in MC40 rats and increased the pituitary protein expression of gonadotropin-releasing hormone receptor (GnRHr) in MC20 rats compared to control rats (p < 0.05). A borderline increase in pituitary lutropin β was observed in MC20 rats compared to control rats (p: 0.09). In addition, MC exposure reduced serum luteinizing hormone (LH) levels in MC40 rats and increased follicle-stimulating hormone (FSH) levels in MC20 and MC40 rats compared to control rats (p < 0.05). MC exposure increased pituitary IL-6 and ED1 protein expression (inflammatory markers) in MC5 rats compared to control (p < 0.05). Additionally, MC exposure borderline increased hypothalamic inducible nitric oxide synthase (iNOS) expression in MC5 compared to control rats (p: 0.06). A negative linear correlation between hypothalamus GnRH and iNOS protein expression was observed (p < 0.05). MC exposure reduced the primary follicles in MC5 and MC40 rats and increased the corpora lutea number in MC20 rats compared to control rats (p < 0.05). An increase in anti-Müllerian hormone (AMH) and progesterone levels were found in MC20 rats, and a decrease in estrogen levels were found in MC5 and MC40 rats (p < 0.05). MC exposure increased ovarian vascular endothelial growth factor receptor (VEGFr), LH receptor (LHr), AMH, ED1, IL-6 and Gp91-phox (oxidative stress marker) protein expression in MC20 rats compared to control rats (p < 0.05). MC increased uterine area and reduced endometrial gland number in MC5 and MC40 rats (p < 0.05). Blunted estrogen-negative feedback was observed in MC40 rats after ovariectomy, with no changes in LH levels compared to intact MC rats (p > 0.05). Therefore, these data suggest that a MC leads to abnormal HPG axis function in female rats.