Exacerbation of innate immune response in mouse primary cultured sertoli cells caused by nanoparticulate TiO₂ involves the TAM/TLR3 signal pathway

Abstract

Sertoli cells provide appropriate mitogens, differentiation factors and sources of energy for developing germ cells throughout the lifetime of males, and protect these germ cells from harmful agents and from the host's own immune system. Therefore, reductions in the rate and quality of spermatogenesis caused by nanoparticulate titanium dioxide (nano-TiO ) may be closely involved in the immunoregulation of Sertoli cells. However, the underlying mechanism of this response is still unclear. To address this issue, we used mouse primary cultured Sertoli cells to examine the toxic effects of nano-TiO via alterations in morphology, cell viability, and activation of the TAM/TLR3 signal pathway. The results demonstrated that nano-TiO could cross the cytomembrane into the cytoplasm or nucleus, decrease Sertoli cell viability, damage morphology (such as elongated fusiform, cellular and nuclear shrinkage) and induce the expression of various immune mediators and inflammatory cytokines, including TLR3(+0.31-fold to +0.81-fold), IL-lβ(+0.33-fold to +5.0-fold), NF-κB(+0.22-fold to +3.65-fold), IL-6(+0.47-fold to +3.53-fold), TNF-α(+0.14-fold to +2.44-fold), IFN-α(+0.17-fold to +2.27-fold), and IFN-β(+0.09-fold to +2.29-fold), and suppress the expression of Tyro3(-9.33% to -61.93%), Axl(-19.03% to -60.67%), Mer(-8.04% to -59.16%), and IκB(-34.35% to -86.59%) in primary cultured Sertoli cells. These results suggest that testicular innate immune responses to pathogens caused by nano-TiO may be involved in the regulatory mechanisms of TAM/TLR3 signaling in testicular Sertoli cells. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 198-208, 2017.

Suppression of testosterone production by nanoparticulate TiO₂ is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells

“…Our experiments clearly demonstrated that nano-TiO 2 reduced the activity of primary cultured rat LCs (Figure 6), entered the cytoplasm and nuclei of cells (Figures 7 and 8), and caused mitochondrial membrane injury (Figure 9), consistent with results obtained with primary cultured mouse or rat Sertoli cells. 42,43 Simultaneously, testosterone production in LCs was significantly lowered following nano-TiO 2 treatment ( Figure 10). Mitochondrial damage is associated with dysfunction of LCs, which are involved mainly in the production and secretion of testosterone.…”

Effects of Titanium Dioxide Nanoparticles on Porcine Prepubertal Sertoli Cells: An “In Vitro” Study

“…The very few studies describing the detrimental effect of TiO 2 NPs on SCs have been performed in mice and rat models under acute exposures (26)(27)(28). However, these experimental conditions may greatly differ from those under which human exposure can potentially occur and often result in conflicting data that are not applicable for risk assessment studies (29).…”