Decreased spermatogenesis led to alterations of testis-specific gene expression in male mice following nano-TiO2 exposure

Hong, Fashui; Zhao, Xiaoyang; Si, Wenhui; Ze, Yuguan; Wang, Ling; Zhou, Yingjun; Hong, Jie; Yu, Xiaohong; Sheng, Lei; Liu, Dong; Xu, Bingqing; Zhang, Jianhao

doi:10.1016/j.jhazmat.2015.08.010

Cited by 63 publications

(71 citation statements)

References 88 publications

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“…Nanomaterials may induce reproductive toxicity, which involves physiological and molecular factors, by disturbing immune balance, which can induce chronic inflammation. TiO 2 NPs have been shown to induce reproductive abnormalities in male animals by reducing fertility and increasing apoptosis/necrosis of spermatogonia and SCs . Importantly, SCs in response to TiO 2 NPs administration resulted in increased inflammatory responses and compromised immunity in the testes which caused a reduction in spermatogenesis in humans and animals.…”

Section: Discussionmentioning

confidence: 99%

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Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

Hong

et al. 2017

J Biomedical Materials Res

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Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO NPs for 24 h, and TiO NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration-dependent manner. Furthermore, immunological dysfunction caused by TiO NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO NPs significantly decreased Ca -ATPase and Ca /Mg -ATPase activity and enhanced intracellular Ca levels, and up-regulated the expression of p-PKC and p-p38 MAPK in a dose-dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca /PKC/p38 MAPK cascade, which triggers NF-κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1374-1382, 2017.

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Section: Discussionmentioning

confidence: 99%

“…Therefore, the safety of TiO 2 NPs should be seriously considered, particularly their reproductive toxicity . For example, TiO 2 NPs decreased sperm concentration and sperm motility, increased the sperm malformation rate, and reduced fertility . However, the mechanism underlying reproductive toxicity is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

Hong

et al. 2017

J Biomedical Materials Res

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“…TiNPs are taken up into Leydig cells to inhibit the viability and proliferation of these cells (Komatsu et al, 2008). Furthermore, TiNPs disrupt the mouse blood-testis barrier with alterations to the expression of several testis-specific genes (Hong et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

High sensitivity of testicular function to titanium nanoparticles

et al. 2017

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-Titanium dioxide nanoparticles (TiNPs) present toxicity in organs such as the liver, lung, and intestine. The testis has also been reported as a target organ of TiNPs. We recently reported that TiNPs had no genotoxic effect in the liver and bone marrow, while showing clear testicular dysfunction. In this paper, therefore, we systematically compared the sensitivity of hepatic function using biochemical markers and testicular function against TiNPs. Male C57BL/6J mice were injected intravenously with TiNPs (Aeroxide-P25, at doses of 0.1, 1, 2, and 10 mg/kg body weight) once per week for 4 consecutive weeks. Mice were sacrificed three days after the last injection. Body weights, liver weights, and testicular-related organ weights were not found to be changed by TiNP treatment. Moreover, TiNPs caused no hepatic damage, as evaluated by alanine aminotransferase and aspartate aminotransferase indexes. The testicular function, however, was clearly impaired by TiNP treatment; reduction in two sperm motion parameters (motile percent and progressive percent) and sperm numbers in cauda epididymides was seen. We observed Ti accumulation in the liver but not in the testis, as well as no change in plasma levels of sex hormones related to spermatogenesis. Our findings indicate that the testis is highly sensitive to TiNPs, as compared to the liver. We believe that, when considering the biological effects of TiNPs, testicular function (especially motility ability) may be a sensitive indicator.

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“…Nanomaterials may induce reproductive toxicity by disturbing immune balance, which can induce chronic inflammation . Nano‐TiO 2 is one such nanomaterial and has been shown to induce reproductive abnormalities in animals by reducing fertility …”

Section: Discussionmentioning

confidence: 99%

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

Hong

Zhou

et al. 2016

J Biomedical Materials Res

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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.

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Decreased spermatogenesis led to alterations of testis-specific gene expression in male mice following nano-TiO2 exposure

Cited by 63 publications

References 88 publications

Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

High sensitivity of testicular function to titanium nanoparticles

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

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Decreased spermatogenesis led to alterations of testis-specific gene expression in male mice following nano-TiO2 exposure

Cited by 63 publications

References 88 publications

Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+/PKC/p38 MAPK/NF‐κB cascade

Toxic effects of TiO2 nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca2+/PKC/p38 MAPK/NF‐κB cascade

High sensitivity of testicular function to titanium nanoparticles

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

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Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

Toxic effects of TiO₂ nanoparticles in primary cultured rat sertoli cells are mediated via a dysregulated Ca²⁺/PKC/p38 MAPK/NF‐κB cascade

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