The obesogen tributyltin induces abnormal ovarian adipogenesis in adult female rats

• DOI: 10.1016/j.toxlet.2018.06.1068
• Publication Date: 2018-06-15T03:53:31Z
• Authors: Julia F.P. de Araújo; Priscila L. Podratz; Gabriela C. Sena; Eduardo Merlo; Leandro C. Freita...; Júlia Gringorini ...; Amanda Fidalgo Zo...; Ana Paula Santos-...; Leandro Miranda-A...; Ian V. Silva; Jones B. Graceli
• Keywords: 0303 health sciences; Adipogenesis; Ovary; Estrous Cycle; Lipid Droplets; Phosphoproteins; Fibrosis; Gene Expression Regulation, Enzymologic; Oxidative Stress; 03 medical and health sciences; Cholesterol; Adipose Tissue; Ovarian Follicle; Animals; Environmental Pollutants; Female; Cholesterol Side-Chain Cleavage Enzyme; Obesity; Atrophy; Gonadal Steroid Hormones; Adiposity; Pelvic Inflammatory Disease

Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-β and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.