Effects of tributyltin on placental cytokine production

Objective: Tributyltin (TBT) is a persistent pollutant but its effects on placental function are poorly understood as are its possible interactions with infection. We hypothesized that TBT alters the production of sex hormones and biomarkers for inflammation and neurodevelopment in an infection-dependent manner. Methods: Placental explant cultures were treated with 0 5000 nM TBT in the presence and absence of Escherichia coli. A conditioned medium was harvested and concentrations of steroids (progesterone, P-4; testosterone, T and estradiol, E-2) as well as biomarkers of inflammation [interleukin (IL-1 beta), tumor necrosis factor (TNF-alpha), IL-10, IL-6, soluble glycoprotein 130 (sgp-130) and heme oxygenase-1 (HO-1)], oxidative stress [8-iso-prostaglandin (8-IsoP)] and neurodevelopment [brain-derived neurotrophic factor (BDNF)] were quantified. Results: TBT increased P-4 slightly but had little or no effect on T or E-2 production. 11-1 beta, IL-6, sgp-130, IL-10 and 8-IsoP production was enhanced by TBT. P-4 and IL-6 production was also enhanced by TBT for bacteria-stimulated cultures but TBT significantly inhibited bacteria-induced 1L-1 beta and sgp-130 production. High doses of TBT also inhibited BDNF production. Conclusions: TBT increases P-4 but has minimal effect on downstream steroids. It enhances the production of inflammatory biomarkers such as IL-1 beta, TNF-alpha, IL-10 and IL-6. Inhibition of sgp-130 by TBT suggests that TBT may increase bioactive 11-6 production which has been associated with adverse neurodevelopmental outcomes. Reduced expression of BDNF also supports this possibility.