A coexposição subaguda ao tributilestanho mais mercúrio prejudica a função do eixo reprodutivo e diminui a fertilidade em ratas
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Data
2025-10-21
Autores
Januário, Cidália de Fátima
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Universidade Federal do Espírito Santo
Resumo
Tributyltin (TBT) and mercury (Hg) are endocrine-disrupting chemicals that individually cause reproductive complications. However, the reproductive consequences of coexposure to a mixture of TBT plus Hg are not well known. We hypothesized that coexposure to a mixture of TBT plus Hg would alter hypothalamic-pituitary-gonadal (HPG) axis function. Female rats were exposed to daily doses of TBT (100 ng/kg/day by gavage), plus doses of Hg (1st dose 4.6 μg/kg IM, subsequent doses of 0.07 μg/kg/day IM), for 15 days, after which chemical accumulation in the tissues, morphology, hormone levels, inflammation, fibrosis, and protein expression in the reproductive organs were assessed. Increases in tin (Sn) and Hg levels were detected in the serum, HPG axis, and uterus of TBT-Hg rats. TBT-Hg rats exhibited irregular estrous cycles. TBT-Hg rats showed an increase in gonadotropin releasing hormone (GnRH) protein expression and follicle-stimulating hormone (FSH) levels and a reduction in luteinizing hormone (LH) levels. Reduced ovarian reserve, antral follicles, corpora lutea (CL) number, and estrogen levels and increased atretic and cystic follicles were found, suggesting that TBT-Hg exposure exacerbated premature ovarian insufficiency (POI) features. Furthermore, TBT-Hg rats exhibited increased ovarian mast cell numbers, expression of the inflammatory markers IL-6 and collagen deposition. Apoptosis and reduced gland number were observed in the uteri of TBT Hg rats. A reduction in the number of pups/litters for 90 days was found in TBT-Hg rats, suggesting impaired fertility. Strong negative correlations were found between serum and ovarian Sn levels and ovarian Hg levels and ovarian reserve and CL number. Collectively, these data suggest that TBT plus Hg exposure leads to abnormalities in the HPG axis, exacerbating POI features and reducing fertility in female rats.
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Tributilestanho , Mercúrio , Coexposição , Falência ovariana prematura , Fertilidade