Effect of Titanium Dioxide Nanoparticles on Male and Female Reproductive Systems

Sanaz Alaee, Mojtaba Ilani


Titanium Dioxide (TiO2) nanoparticle has a wide range of application in industrial and consumer products especially in cosmetics such as high sun protection factor creams in order to protect the skin from UV light. In spite of its increased production and use there is not enough epidemiological data regarding TiO2 nanoparticle toxicity. Toxic effects of TiO 2 nanoparticles on human reproductive systems have been investigated by many studies mostly by employing animal models, but results are extremely conflicted and inconsistent. In this review we summarized published data about the effects of TiO2 nanoparticle on male and female reproductive systems to clarify its possible toxic effects on reproduction and fertility.

Full Text:



Nematbakhsh H, Talaiekhozani A, Ahmadvand F. [An overview on application of nonotechnology in environmental engineering (Persian)].Paper presented at: The 4th Conference of Nano-Technology From Theory to Application; 4 February 2016; Isfahan, Iran.

El-Ansary A, Al-Daihan S. On the toxicity of therapeutically used nanoparticles: An overview. Journal of Toxicology. 2009; 1–9. doi: 10.1155/2009/754810

De Stefano D, Carnuccio R, Maiuri MC. Nanomaterials toxicity and cell death modalities. Journal of Drug Delivery. 2012; 1–14. doi: 10.1155/2012/167896.

Iavicoli I, Leso V, Bergamaschi A. Toxicological effects of titanium dioxide nanoparticles: A review of in vivostudies. Journal of Nanomaterials. 2012; 1–36. doi: 10.1155/2012/964381.

Heringa MB, Geraets L, van Eijkeren JCH, Vandebriel RJ, de Jong WH, Oomen AG. Risk assessment of titanium dioxide nanoparticles via oral exposure, including toxicokinetic considerations. Nanotoxicology. 2016; 10(10):1515–25. doi: 10.1080/17435390.2016.1238113

Exbrayat JM, Moudilou EN, Lapied E. Harmful effects of nanoparticles on animals. Journal of Nanotechnology. 2015; 1–10. doi: 10.1155/2015/86109

Rana S, Kalaichelvan PT. Ecotoxicity of nanoparticles. ISRN Toxicology. 2013; 1–11. doi: 10.1155/2013/574648

Preaubert L, Courbiere B, Achard V, Tassistro V, Greco F, Orsiere T, et al. Cerium dioxide nanoparticles affectin vitrofertilization in mice. Nanotoxicology. 2015; 1–7. doi: 10.3109/17435390.2015.1030792

Tiedemann D, Taylor U, Rehbock C, Jakobi J, Klein S, Kues WA, et al. Reprotoxicity of gold, silver, and gold–silver alloy nanoparticles on mammalian gametes. The Analyst. 2014; 139(5):931–42. doi: 10.1039/c3an01463k

Hen SX, Yang XZ, Deng Y, Huang J, Li Y, Sun Q, et al. Silver nanoparticles induce oocyte maturation in zebrafish (Danio rerio). Chemosphere. 2017; 170:51–60. doi: 10.1016/j.chemosphere.2016.12.016

Li WJ, Zhou XL, Liu BL, Dai JJ, Song P, Teng Y. Effect of nanoparticles on the survival and development of vitrified porcine GV oocytes. CryoLetters. 2016; 37(6): 401-405. PMID: 28072426

Jin Z, Li R, Zhou C, Shi L, Zhang X, Yang Z, et al. Efficient gene knockdown in mouse oocytes through peptide nanoparticle-mediated sirna transfection. PLoS ONE. 2016; 11(3):e0150462. doi: 10.1371/journal.pone.0150462

Li R, Jin Z, Gao L, Liu P, Yang Z, Zhang D. Effective protein inhibition in intact mouse oocytes through peptide nanoparticle-mediated antibody transfection. PeerJ. 2016; 4:1849. doi: 10.7717/peerj.1849

Rather MA, Sharma R, Gupta S, Ferosekhan S, Ramya VL, Jadhao SB. Chitosan-nanoconjugated hormone nanoparticles for sustained surge of gonadotropins and enhanced reproductive output in female fish. PLoS ONE. 2013; 8(2):e57094. doi: 10.1371/journal.pone.0057094

Sutovsky P, Aarabi M, Miranda-Vizuete A, Oko R. Negative biomarker based male fertility evaluation: Sperm phenotypes associated with molecular-level anomalies. Asian Journal of Andrology. 2015; 17(4):554. doi: 10.4103/1008-682x.153847

Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: A review of current toxicological data. Particle and Fibre Toxicology. 2013; 10(1):15. doi: 10.1186/1743-8977-10-15

Wiesenthal A, Hunter L, Wang S, Wickliffe J, Wilkerson M. Nanoparticles: small and mighty. International Journal of Dermatology. 2011; 50(3):247–54. doi: 10.1111/j.1365-4632.2010.04815.x

Szaciłowski K, Macyk W, Drzewiecka-Matuszek A, Brindell M, Stochel G. Bioinorganic photochemistry: Frontiers and mechanisms. Chemical Reviews. 2005; 105(6):2647–94. doi: 10.1021/cr030707e

Chen Z, Wang Y, Ba T, Li Y, Pu J, Chen T, et al. Genotoxic evaluation of titanium dioxide nanoparticles in vivo and in vitro. Toxicology Letters. 2014; 226(3):314–9. doi: 10.1016/j.toxlet.2014.02.020

Wang JX, Li YF, Zhou GQ, Li B, Jiao F, Chen CY, et al. Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time. Zhonghua yu fang yi xue za zhi. 2007; 41(2): 91-95. PMID: 17605232

Di Bucchianico S, Cappellini F, Le Bihanic F, Zhang Y, Dreij K, Karlsson HL. Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry. Mutagenesis. 2016; 32(1):127–37. doi: 10.1093/mutage/gew030

Sadiq R, Bhalli JA, Yan J, Woodruff RS, Pearce MG, Li Y, et al. Genotoxicity of TiO2 anatase nanoparticles in B6C3F1 male mice evaluated using Pig-a and flow cytometric micronucleus assays. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2012; 745(1-2):65–72. doi: 10.1016/j.mrgentox.2012.02.002

Shimizu M, Tainaka H, Oba T, Mizuo K, Umezawa M, Takeda K. Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Particle and Fibre Toxicology. 2009; 6(1):20. doi: 10.1186/1743-8977-6-20

Chang X, Zhang Y, Tang M, Wang B. Health effects of exposure to nano-TiO2: A meta-analysis of experimental studies. Nanoscale Research Letters. 2013; 8(1):51. doi: 10.1186/1556-276x-8-51

Xie G, Wang C, Sun J, Zhong G. Tissue distribution and excretion of intravenously administered titanium dioxide nanoparticles. Toxicology Letters. 2011; 205(1):55–61. doi: 10.1016/j.toxlet.2011.04.034

Wang J, Zhou G, Chen C, Yu H, Wang T, Ma Y, et al. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicology Letters. 2007; 168(2):176–85. doi: 10.1016/j.toxlet.2006.12.001

Sun J, Zhang Q, Wang Z, Yan B. Effects of nanotoxicity on female reproductivity and fetal development in animal models. International Journal of Molecular Sciences. 2013; 14(5):9319–37. doi: 10.3390/ijms14059319

Dehghani N, Noori A, Modaresi M. Investigating the effect of titanium dioxide nanoparticles on the growth and sexual maturation of male rats. International Journal of Basic Sciences and Applied Research. 2014; 3(11): 772-776.

Gao G, Ze Y, Zhao X, Sang X, Zheng L, Ze X, et al. Titanium dioxide nanoparticle-induced testicular damage, spermatogenesis suppression, and gene expression alterations in male mice. Journal of Hazardous Materials. 2013; 258-259:133–43. doi: 10.1016/j.jhazmat.2013.04.046

Guo LL, Liu XH, Qin DX, Gao L, Zhang HM, Liu JY, et al. Effects of nanosized titanium dioxide on the reproductive system of male mice. National Journal of Andrology. 2009; 15(6): 517-522. PMID: 19593991

Mohammadi Fartkhooni F, Noori A, Momayez M, Sadeghi L, Shirani K, Yousefi Babadi V. The effects of nano titanium dioxide (TiO2) in spermatogenesis in wistar rat. European Journal of Experimental Biology. 2013; 3(4): 145-149.

Hong F, Si W, Zhao X, Wang L, Zhou Y, Chen M, et al. TiO2 nanoparticle exposure decreases spermatogenesis via biochemical dysfunctions in the testis of male mice. Journal of Agricultural and Food Chemistry. 2015; 63(31):7084–92. doi: 10.1021/acs.jafc.5b02652

Bakare AA, Udoakang AJ, Anifowoshe AT, Fadoju OM, Ogunsuyi OI, Alabi OA, et al. Genotoxicity of titanium dioxide nanoparticles using the mouse bone marrow micronucleus and sperm morphology assays. Journal of Pollution Effects & Control. 2016; 04(02). doi: 10.4172/2375-4397.1000156

Ye L, Hong F, Ze X, Li L, Zhou Y, Ze Y. Toxic effects of TiO2 nanoparticles in primary cultured rat Sertoli cells are mediated via a dysregulated Ca2+/PKC/p38 MAPK/NF-κB cascade. Journal of Biomedical Materials Research Part A. 2017; 105(5):1374–82. doi: 10.1002/jbm.a.36021

Morgan AM, Ibrahim MA, Noshy PA. Reproductive toxicity provoked by titanium dioxide nanoparticles and the ameliorative role of Tiron in adult male rats. Biochemical and Biophysical Research Communications. 2017; 486(2):595–600. doi: 10.1016/j.bbrc.2017.03.098

Zhao X, Ze Y, Gao G, Sang X, Li B, Gui S, et al. Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice. PLoS ONE. 2013; 8(4):e59378. doi: 10.1371/journal.pone.0059378

Tassinari R, Cubadda F, Moracci G, Aureli F, D’Amato M, Valeri M, et al. Oral, short-term exposure to titanium dioxide nanoparticles in Sprague-Dawley rat: Focus on reproductive and endocrine systems and spleen. Nanotoxicology. 2013; 8(6):654–62. doi: 10.3109/17435390.2013.822114

Gao G, Ze Y, Li B, Zhao X, Zhang T, Sheng L, et al. Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles. Journal of Hazardous Materials. 2012; 243:19–27. doi: 10.1016/j.jhazmat.2012.08.049

Yoosefi M, Heydari N, Faruqui Sana S, Azarkian M, Sadri S, Eslami M, et al. The effects of titanium dioxide nanoparticles on sexual hormone sin female mice. Der Pharmacia Lettre. 2015; 7(10):142-146.

Yoosefi M, Shariat S, Golabi M, Safaei M, Heydari N, Kaji Andish, et al. The effects of titanium dioxide nanoparticles on pituitary-gonad axis in male mice. Journal of Chemical and Pharmaceutical Research. 2015; 7(10): 720-723.

Yamashita K, Yoshioka Y, Higashisaka K, Mimura K, Morishita Y, Nozaki M, et al. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nature Nanotechnology. 2011; 6(5):321–8. doi: 10.1038/nnano.2011.41

Takeda K, Suzuki K, Ishihara A, Kubo-Irie M, Fujimoto R, Tabata M, et al. Nanoparticlestransferred from pregnant mice to their offspring can damage the genital and cranial nerve systems. Journal of Health Science.2009; 55(1):95–102. doi: 10.1248/jhs.55.95

Jackson P, Halappanavar S, Hougaard KS, Williams A, Madsen AM, Lamson JS, et al. Maternal inhalation of surface-coated nanosized titanium dioxide (UV-Titan) in C57BL/6 mice: Effects in prenatally exposed offspring on hepatic DNA damage and gene expression. Nanotoxicology. 2011; 7(1):85–96. doi: 10.3109/17435390.2011.633715

Hou J, Wan X, Wang F, Xu G, Liu Z, Zhang T. Effects of titanium dioxide nanoparticles on development and maturation of rat preantral follicle in vitro. Academic Journal of Second Military Medical University. 2009; 29(8):869–73. doi: 10.3724/sp.j.1008.2009.00869

DOI: http://dx.doi.org/10.18869%2Fnrip.jamsat.3.1.3


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

pISSN: 2423-5903                                             eISSN: 2538-4473