Obesogenic Tributyltin Leads to Abnormal Ovarian Steroidogenesis, Lipids Accumulation and Oxidative Stress in Female Rats

Presentation Number: SAT 250
Date of Presentation: April 1st, 2017

Julia F P Araújo*1, Priscila Lang Podratz1, Gabriela Cavati Sena2, Eduardo Merlo1, Leandro C Freitas-Lima1, Ana Paula Santos-Silva3, Leandro Miranda-Alves4, Ian Victor Silva1 and Jones B Graceli5
1Federal University of Espirito Santo, Vitoria, Brazil, 2Federal University of Espirito Santo, Vitória, BRAZIL, 3Federal University of Rio de Janeiro, 4Federal University of Rio de Janeiro, Rio de Janeiro, BRAZIL, 5Federal University of Espirito Santo, Vitoria, BRAZIL

Abstract

Tributyltin chloride (TBT) is a xenobiotic used as a biocide that has been demonstrated to induce endocrine-disrupting effects, such as obesity and metabolic abnormalities. Obesity is associated with abnormal adiposity resulting in a low-grade inflammation state and oxidative stress (OS) augmentation, which leads a reproductive function alterations. However, studies that have investigated the obesogenic TBT effects in the ovarian steroidogenesis and OS are especially rare. Here, we describe the reproductive characterization as result of TBT exposure in female rats. To study whether TBT disrupted ovarian steroidogenesis and cellular redox balance, we administered vehicle (CON, 0.4% ethanol) and TBT (TBT, 100 ng/kg/day) in the Wistar female rats for 30 days via gavage. TBT rats displayed a higher body weight (CON:219,5±1,69 vs TBT:243.17±3,82 g; p≤0.01; n=6-10) and adiposity (CON:2,69±0,25 vs TBT:3,94±0,38 g/g; p≤0.01; n=6-10). TBT rats exhibited abnormal estrous cyclicity, showing more days in the metestrus-diestrus phase (CON:2,61±0,17 vs TBT:3,47±0,18 d; p≤0.05; n=8-10). No significant changes were observed in basal serum LH levels in CON and TBT rats (CON:2,18±0,27 vs TBT:2,29±0,19 mU/ml; p≥0.05, n=8-10). TBT rats had higher testosterone (CON:0,25±0,02 vs TBT:0,35±0,02 ng/mL; p≤0.05; n=5-6) and lower estrogen levels (CON: 45,87±2,12 vs TBT:22,58±0,95 pg/mL; p≤0.01; n=5-6). An increased in CYP11β protein expression was observed in TBT ovaries using immunobloting assay (CON:1,0±0,01 vs TBT:1,18±0,07; p≤0.01; n=5). No significant change in the StAr mRNA expression in TBT ovaries (CON:1,05±0,036 vs TBT:1,18±0,1; p≥0.05, n=5). Abnormal thickness of granulosa and theca cell layer was observed in TBT ovarian follicles. Irregular ovarian follicular development, raised atretic and cystic follicles and reduced corpora lutea number was noted in TBT ovaries (CON:5,13±0,55 vs TBT:3,24±0,49 follicles/mm2; p≤0.01; n=5). Further, ovary and uterus atrophy, fibrosis and apoptosis was observed in TBT rats, as well the ovarian and uterine inflammation (p≤0.05; n=4-8). An increased OS was identified in the TBT ovaries using DHE assay (CON:9203,87±1093,56 vs TBT:16638,01±1814,69; p≤0.01; n=5). Interestingly, an increase in the cholesterol levels (CON:106,49±0,34 vs TBT:115,51±1,65 g; p≤0.01; n=5) and lipid droplet accumulation was observed in the ovaries of TBT rats using Oil Red O stain (CON:4,95±0,22 vs TBT:6,88±0,39 %; p≤0.001; n=5). Ovary PPARγ expression was higher in TBT rats (CON:1,0±0,03 vs TBT:1,25±0,02; p≤0.01; n=5). Thus, TBT disrupted proper functioning of the ovarian steroidogenesis as a result of lipids accumulation and abnormal cellular redox balance signalling. This work supports the hypothesis that TBT impairs the normal ovarian control in the reproductive tract.

 

Nothing to Disclose: JFPA, PLP, GCS, EM, LCF, APS, LM, IVS, JBG