Evaluation of Lipids and Lipid-Related Transcripts in Human and Ovine Theca Cells and an in Vitro Mouse Model Exposed to the Obesogen Chemical Tributyltin.

BACKGROUND: Exposure to obesogenic chemicals has been reported to result in enhanced adipogenesis, higher adipose tissue accumulation, and reduced ovarian hormonal synthesis and follicular function. We have reported that organotins [tributyltin (TBT) and triphenyltin (TPT)] dysregulate cholesterol trafficking in ovarian theca cells, but, whether organotins also exert lipogenic effects on ovarian cells remains unexplored. OBJECTIVE: We investigated if environmentally relevant exposures to organotins [TBT, TPT, or dibutyltin (DBT)] induce lipid dysregulation in ovarian theca cells and the role of the liver X receptor (LXR) in this effect. We also tested the effect of TBT on oocyte maturation and neutral lipid accumulation, and lipid-related transcript expression in cumulus cells and preimplantation embryos. METHODS: Primary theca cell cultures derived from human and ovine ovaries were exposed to TBT, TPT, or DBT (1, 10, or 50 ng/ml). The effect of these chemical exposures on neutral lipid accumulation, lipid abundance and composition, lipid homeostasis-related gene expression, and cytokine secretion was evaluated using liquid chromatography-mass spectrometry (LC-MS), inhibitor-based methods, cytokine secretion, and lipid ontology analyses. We also exposed murine cumulus-oocyte complexes to TBT and evaluated oocyte maturation, embryo development, and lipid homeostasis-related mRNA expression in cumulus cells and blastocysts. RESULTS: Exposure to TBT resulted in higher intracellular neutral lipids in human and ovine primary theca cells. In ovine theca cells, this effect was dose-dependent, independent of cell stage, and partially mediated by LXR. DBT and TPT resulted in higher intracellular neutral lipids but to a lesser extent in comparison with TBT. More than 140 lipids and 9 cytokines were dysregulated in TBT-exposed human theca cells. Expression of genes involved in lipogenesis and fatty acid synthesis were higher in theca cells, as well as in cumulus cells and blastocysts exposed to TBT. However, TBT did not impact the rates of oocyte maturation or blastocyst development. DISCUSSION: TBT induced dyslipidemia in primary human and ovine theca cells, which may be responsible for some of the TBT-induced fertility dysregulations reported in rodent models of TBT exposure. https://doi.org/10.1289/EHP13955.

Synergistic Steatosis Induction in Mice: Exploring the Interactions and Underlying Mechanisms between PFOA and Tributyltin.

This study explores the impact of environmental pollutants on nuclear receptors (CAR, PXR, PPARα, PPARγ, FXR, and LXR) and their heterodimerization partner, the Retinoid X Receptor (RXR). Such interaction may contribute to the onset of non-alcoholic fatty liver disease (NAFLD), which is initially characterized by steatosis and potentially progresses to steatohepatitis and fibrosis. Epidemiological studies have linked NAFLD occurrence to the exposure to environmental contaminants like PFAS. This study aims to assess the simultaneous activation of nuclear receptors via perfluorooctanoic acid (PFOA) and RXR coactivation via Tributyltin (TBT), examining their combined effects on steatogenic mechanisms. Mice were exposed to PFOA (10 mg/kg/day), TBT (5 mg/kg/day) or a combination of them for three days. Mechanisms underlying hepatic steatosis were explored by measuring nuclear receptor target gene and lipid metabolism key gene expressions, by quantifying plasma lipids and hepatic damage markers. This study elucidated the involvement of the Liver X Receptor (LXR) in the combined effect on steatosis and highlighted the permissive nature of the LXR/RXR heterodimer. Antagonistic effects of TBT on the PFOA-induced activation of the Pregnane X Receptor (PXR) and Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) were also observed. Overall, this study revealed complex interactions between PFOA and TBT, shedding light on their combined impact on liver health.

Activity of Tri-N-Butyl Tin maleate in carpets against Staphylococcus aureus and Aspergillus niger, verified through two methodologies: Inhibition Halo (HZ) and Inhibition Surface (Print) / Atividade de tri-n-butyl tin maleate em carpetes contra Staphylococcus aureus e Aspergillus niger, verificada através de duas metodologias: Zona de Inibição (ZI) e Superfície de Inibição (Impressão)

The aim of the present study was to verify the activity of the Tri-N-Butyl Tin maleate compound against Staphylococcus aureus and Aspergillus niger, after its industrial application in 40 samples of carpets of different materials (polypropylene, polyester, polyamide and wool). The qualitative assays were performed through two methodologies: Inhibition Halo (HZ) and Inhibition of Surface (Print). The carpet with the product inhibited 100 percent of bacterial (Staphylococcus aureus) and fungi (Aspergillus niger) growth, under the conditions of this study. The microbial inhibition was higher in upper portion of carpets. The methodologies employed appear to be adequate to test the bactericide and fungicide activities of the Tri-N-Butyl Tin maleate. The print methodology confirmed the results obtained by the inhibition zone assay. Further studies using the same methodologies are needed to confirm our results.

O objetivo do presente estudo foi verificar a atividade do composto maleato de estanho tri-n-butílico contra Staphylococcus aureus e Aspergillus niger, após sua aplicação industrial em 40 amostras de carpetes de diferentes materiais (polipropileno, poliéster, poliamida e lã). Os ensaios qualitativos foram realizados através de duas metodologias: Zona de Inibição (ZI) e Superfície de Inibição (Impressão). Os carpetes tratados com o produto apresentaram 100 por cento de inibição de crescimento bacteriano (Staphylococcus aureus) e fúngico (Aspergillus niger), sob as condições desse estudo. A inibição de crescimento microbiano foi mais elevada na porção superior dos carpetes. As metodologias empregadas parecem ser adequadas para testar a atividade bactericida e fungicida do maleato de estanho tri-n-butílico. A metodologia de impressão confirmou os resultados obtidos no ensaio de zona de inibição. Estudos futuros utilizando as mesmas metodologias são necessários para confirmação destes dados.