Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats.

Autor: Sena GC; Department of Morphology, Federal University of Espírito Santo, Brazil., Freitas-Lima LC; Department of Morphology, Federal University of Espírito Santo, Brazil., Merlo E; Department of Morphology, Federal University of Espírito Santo, Brazil., Podratz PL; Department of Morphology, Federal University of Espírito Santo, Brazil., de Araújo JF; Department of Morphology, Federal University of Espírito Santo, Brazil., Brandão PA; Department of Chemistry, Federal University of Espírito Santo, Brazil., Carneiro MT; Department of Chemistry, Federal University of Espírito Santo, Brazil., Zicker MC; Department of Food Science, Faculty of Pharmacy, Federal University of Minas Gerais, Brazil., Ferreira AV; Department of Basic Nursing, Nursing School, Federal University of Minas Gerais, Brazil., Takiya CM; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil., de Lemos Barbosa CM; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil., Morales MM; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil., Santos-Silva AP; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil; Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro, Brazil., Miranda-Alves L; Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro, Brazil., Silva IV; Department of Morphology, Federal University of Espírito Santo, Brazil., Graceli JB; Department of Morphology, Federal University of Espírito Santo, Brazil. Electronic address: jbgraceli@gmail.com.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2017 Mar 15; Vol. 319, pp. 22-38. Date of Electronic Publication: 2017 Feb 02.
DOI: 10.1016/j.taap.2017.01.021
Abstrakt: Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be associated with abnormal HPG function. A strong negative correlation between the hyperleptinemia and lower Kiss responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads to toxic effects direct on the HPG axis and/or indirectly by abnormal metabolic regulation of the HPG axis.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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