Name: GABRIELA CAVATI SENA
Publication date: 14/03/2017
Advisor:
Name |
Role |
|---|---|
| JONES BERNARDES GRACELI | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| JONES BERNARDES GRACELI | Advisor * |
| LEANDRO CEOTTO FREITAS LIMA | External Examiner * |
| LEONARDO DOS SANTOS | Internal Examiner * |
| NAZARE SOUZA BISSOLI | Internal Examiner * |
Summary: 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. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin action. An integrative metabolic control in the HPG axis was exerted by leptin. However, studies that investigate the obesogenic TBT effects on the HPG axis are especially rare. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days 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, kisspeptin 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 kisspeptin responsiveness. A strong negative correlation between the serum and ovary tin levels with lower kisspeptin 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 TBT rats. We also identified: an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hiperleptinemia and hypoadiponectinemia. TBT disrupted proper functioning of the HPG axis as a result of abnormal kisspeptin 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 kisspeptin responsiveness was observed in the TBT rats. These findings provide evidence that TBT leads toxic effects direct on the HPG axis and/ or indirectly by abnormal metabolic regulation of the axis.
