title: Exposure to TiO2 Nanoparticles Induces Immunological Dysfunction in Mouse Testitis.
abstract: Although TiO2 nanoparticles (NPs) as endocrine disruptors have been demonstrated to be able to cross the blood-testis barriers and induce reproductive toxicity in male animals, whether the reproductive toxicity of male animals due to exposure to endocrine disruptor TiO2 NPs is related to immunological dysfunction in the testis remains not well understood. This study determined whether the reproductive toxicity and immunological dysfunction induced by exposure to TiO2 NPs is associated with activation or inhibition of TAM/TLR-mediated signal pathway in mouse testis. The results showed that male mice exhibited significant reduction of fertility, infiltration of inflammatory cells, rarefaction, apoptosis, and/or necrosis of spermatogenic cells and Sertoli cells due to TiO2 NPs. Furthermore, these were associated with decreased expression of Tyro3 (-18.16 to -66.6%), Axl (-14.7 to -57.99%), Mer (-7.98 to -72.62%), and IκB (-11.25 to -63.16%), suppression of cytokine signaling (SOCS) 1 (-21.99 to -73.8%) and SOCS3 (-8.11 to -34.86%), and increased expression of Toll-like receptor (TLR)-3 (21.4-156.03%), TLR-4 (37.0-109.87%), nuclear factor-κB (14.75-69.34%), interleukin (IL)-lβ (46.15-123.08%), IL-6 (2.54-81.98%), tumor necrosis factor-α (6.95-88.39%), interferon (IFN)-α (2.54-37.25%), and IFN-β (10.19-80.56%), which are involved in the immune environment in the testis. The findings showed that reproductive toxicity of male mice induced by exposure to endocrine disruptor TiO2 NPs may be associated with biomarkers of impairment of immune environment or dysfunction of TAM/TLR3-mediated signal pathway in mouse testitis. Therefore, the potential risks to reproductive health should be attended, especially in those who are occupationally exposed to TiO2 NPs.
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Yushuang
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University , Huaian 223300, China.|Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Huaiyin Normal University , Huaian 223300, China.|School of Life Sciences, Huaiyin Normal University , Huaian 223300, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Medical College of Soochow University , Suzhou 215123, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.affiliation: Library of Soochow University , Suzhou 215123, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000633:toxicity*; D009920:Orchitis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology; D013737:Testis / Q000187:drug effects / Q000276:immunology; D014025:Titanium / Q000633:toxicity*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C009495:titanium dioxide; D014025:Titanium; D020794:Receptor Protein-Tyrosine Kinases; C513478:Tyro3 protein, mouse; D000094963:Axl Receptor Tyrosine Kinase
keywords: TAM/TLRs signal pathway; immune dysfunction; reproductive toxicity; testitis; titanium dioxide nanoparticles