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Danafar, A., Khoradmehr, A., Hosseini Bondarabadi, M., Mazaheri, F., Tamadon, A., Pourmasoumi, S., Gholizadeh, L., Moshref, M., Halvaei, I., Hosseini, A., Golzadeh, J., Rahiminia, T., & Anvari, M. (2022). Impairment of sperm efficiency in mice following short-term nano-titanium dioxide exposure: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 19(12), 1045-1058. https://doi.org/10.18502/ijrm.v19i12.10055
https://doi.org/10.18502/ijrm.v19i12.10055
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- Cited by 3 articles
authors
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Amirhossein Danafar
Amirhossein Danafar
Dr. Seyedhassani Medical Sciences Center, Yazd, Iran.
-
Arezoo Khoradmehr
Arezoo Khoradmehr
The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.
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Mahya Hosseini Bondarabadi
Mahya Hosseini Bondarabadi
Université Clermont Auvergne, CNRS, LMGE, Clermont-Ferrand, France.
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Fahime Mazaheri
Fahime Mazaheri
Research and Clinical Center of Infertility, Yazd Reproductive Science Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Amin Tamadon
Amin Tamadon
The Persian Gulf Marine Biotechnology Research Center, the Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.
-
Soheila Pourmasoumi
Soheila Pourmasoumi
Non-Communicable Diseases Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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Lida Gholizadeh
Lida Gholizadeh
Research and Clinical Center of Infertility, Yazd Reproductive Science Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Mojgan Moshref
Mojgan Moshref
Research and Clinical Center of Infertility, Yazd Reproductive Science Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Iman Halvaei
Iman Halvaei
Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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Akram Hosseini
Akram Hosseini
Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
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Jalal Golzadeh
Jalal Golzadeh
Stem Cell Biology Research Center, Yazd Reproductive Science Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Tahereh Rahiminia
Tahereh Rahiminia
Gametogenesis Research Center, Fertility and Infertility Center, Kashan University of Medical Sciences, Kashan, Iran.
-
Morteza Anvari
Morteza Anvari
Research and Clinical Center of Infertility, Yazd Reproductive Science Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Published Date
- Jan 12, 2022
Impairment of sperm efficiency in mice following short-term nano-titanium dioxide exposure: An experimental study
Abstract
Background: Titanium dioxide nanoparticles (TiO2NPs) are widely used in many compounds. Recent evidence has displayed some cytotoxic effects of TiO2NPs on male reproduction.
Objective: The effects of TiO2NP administration on sperm parameters and chromatin and seminiferous histopathology of male mice were investigated.
Materials and Methods: In this experimental study, 32 NMRI male mice (35 ± 3 gr, 8-12-week-old) were divided into four groups (n = 8/each): treated groups were fed orally with 2.5 (group I), 5 (group II) and 10 (group III) mg/kg/day TiO2NPs for 40 days and the control group received phosphate buffered saline. Sperm parameters, DNA integrity and chromatin quality were assessed using chromomycin A3, aniline blue, toluidine blue staining and TUNEL. Hematoxylin eosin staining was performed to measure spermatogenic cells and the total diameter of seminiferous tubules. Also, sex hormone and malondyaldehyde levels were measured.
Results: Abnormal sperm tails rose in group III (28.87 ± 4.91) in comparison with the control group (12.75 ± 3.95). However, chromomycin A3 staining and TUNEL showed higher levels in group III in comparison with the control group, whereas aniline blue and toluidine blue staining showed no differences. A significantly lower spermatogenesis index and lumen parameters were observed in group III. Leydig cell numbers, cellular diameters and the area of the seminiferous tubules were lower in the treated groups. The testosterone level was also lower in these groups and the percentage of malondyaldehyde in the seminal fluid was higher.
Conclusion: Exact mechanisms of TiO2NPs are not clear; however, cytotoxic and genotoxic effects of TiO2NPs may relate to oxidative stress. Given their widespread use, TiO2NPs should be a public health focus of attention.
Key words: Titanium dioxide, Spermatogenesis, Histology, Mouse, Chromatin, TUNEL.
References
[1] Akasaka H, Mukumoto N, Nakayama M, Wang T, Yada R, Shimizu Y, et al. Investigation of the potential of using TiO 2 nanoparticles as a contrast agent in computed tomography and magnetic resonance imaging. Appl Nanosci 2020; 10: 3143–3148.
[2] Powell JJ, Faria N, Thomas-McKay E, Pele LC. Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. J Autoimmun 2010; 34: J226–J233.
[3] Chaudhry Q, Scotter M, Blackburn J, Ross B, Boxall A, Castle L, et al. Applications and implications of nanotechnologies for the food sector. Food Addit Contam 2008; 25: 241–258.
[4] Peters RJB, van Bemmel G, Herrera-Rivera Z, Helsper HPFG, Marvin HJP, Weigel S, et al. Characterization of titanium dioxide nanoparticles in food products: Analytical methods to define nanoparticles. J Agric Food Chem 2014; 62: 6285–6293.
[5] Zhao L, Zhu Y, Chen Z, Xu H, Zhou J, Tang S, et al. Cardiopulmonary effects induced by occupational exposure to titanium dioxide nanoparticles. Nanotoxicology 2018; 12: 169–184.
[6] Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L. Potential adverse effects of nanoparticles on the reproductive system. Int J Nanomedicine 2018; 13: 8487–8506.
[7] Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC. In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 2005; 88: 412–419.
[8] Asare N, Instanes Ch, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, et al. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology 2012; 291: 65–72.
[9] 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. J Hazard Mater 2013; 258: 133–143.
[10] Lu Y, Luo B, Li J, Dai J. Perfluorooctanoic acid disrupts the blood-testis barrier and activates the TNFa/p38 MAPK signaling pathway in vivo and in vitro. Arch Toxicol 2016; 90: 971–983.
[11] Zhu Z, Kawai T, Umehara T, Hoque SM, Zeng W, Shimada M. Negative effects of ROS generated during linear sperm motility on gene expression and ATP generation in boar sperm mitochondria. Free Radic Biol Med 2019; 141: 159–171.
[12] Layali E, Tahmasbpour E, Jorsaraei SGhA. Effects of silver nanoparticles on lipid peroxidation and quality of sperm parameters in male rats. J Babol Univ Med Sci 2016; 18: 48–55.
[13] Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl 2014; 16: 31–38.
[14] 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 2014; 8: 654–662.
[15] 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. Euro J Exp Bio 2013; 3: 145–149.
[16] Ogunsuyi OM, Ogunsuyi OI, Akanni O, Alabi OA, Alimba CG, Adaramoye OA, et al. Alteration of sperm parameters and reproductive hormones in Swiss mice via oxidative stress after co-exposure to titanium dioxide and zinc oxide nanoparticles. Andrologia 2020; 52: e13758.
[17] Sabour M, Khoradmehr A, Kalantar SM, Danafar AH, Omidi M, Halvaei I, et al. Administration of high dose of methamphetamine has detrimental effects on sperm parameters and DNA integrity in mice. Int J Reprod Biomed 2017; 15: 161–168.
[18] Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME, et al. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report. Reprod Toxicol 1996; 10: 237–244.
[19] Nazar M, Talebi AR, Sharifabad MH, Abbasi A, Khoradmehr A, Danafar AH. Acute and chronic effects of gold nanoparticles on sperm parameters and chromatin structure in Mice. Int J Reprod Biomed 2016; 14: 637–642.
[20] Bahaodini A, Owjfard M, Tamadon A, Jafari SM. Low frequency electromagnetic fields long-term exposure effects on testicular histology, sperm quality and testosterone levels of male rats. Asian Pac J Reprod 2015; 4: 195–200.
[21] Panahi M, Keshavarz S, Rahmanifar F, Tamadon A, Mehrabani D, Karimaghai N, et al. Busulfan induced azoospermia: Stereological evaluation of testes in rat. Vet Res Forum 2015; 6: 273–278.
[22] Panahi M, Karimaghai N, Rahmanifar F, Tamadon A, Vahdati A, Mehrabani D, et al. Stereological evaluation of testes in busulfan-induced infertility of hamster. Comparat Clin Pathol 2015; 24: 1051– 1056.
[23] Khoradmehr A, Danafar AH, Halvaei I, Golzadeh J, Hosseini M, Mirjalili T, et al. Effect of prenatal methamphetamine administration during gestational days on mice. Iran J Reprod Med 2015; 13: 41–48.
[24] Bandegi L, Anvari M, Vakili M, Khoradmehr A, Mirjalili A, Talebi AR. Effects of antidepressants on parameters, melondiadehyde, and diphenyl-2- picryl-hydrazyl levels in mice spermatozoa. Int J Reprod Biomed 2018; 16: 365–372.
[25] Zeb A, Ullah F. A simple spectrophotometric method for the determination of thiobarbituric acid reactive substances in fried fast foods. J Anal Method Chem 2016; 2016: 9412767.
[26] Keramati Khiarak B, Karimipour M, Ahmadi A, Farjah GhH. Effects of oral administration of titanium dioxide particles on sperm parameters and in vitro fertilization potential in mice: A comparison between nano-and fine-sized particles. Vet Res Forum 2020; 11: 401–408.
[27] Sabeti P, Pourmasumi S, Rahiminia T, Akyash F, Talebi AR. Etiologies of sperm oxidative stress. Int J Reprod Biomed 2016; 14: 231–240.
[28] Lu T, Ling Ch, Hu M, Meng X, Deng Y, An H, et al. Effect of nano-titanium dioxide on bloodtestis barrier and MAPK signaling pathway in male mice. Biol Trace Elem Res 2021; 199: 2961–2971.
[29] Smith MA, Michael R, Aravindan RG, Dash S, Shah SI, Galileo DS, et al. Anatase titanium dioxide nanoparticles in mice: Evidence for induced structural and functional sperm defects after short-, but not long-, term exposure. Asian J Androl 2015; 17: 261–268.
[30] Morgan AM, Abd El-Hamid MI, Noshy PA. Reproductive toxicity investigation of titanium dioxide nanoparticles in male albino rats. World J Pharm Pharmaceut Sci 2015; 4: 34–49.
[31] 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. J Agric Food Chem 2015; 63: 7084–7092
[32] Ribas-Maynou J, García-Peiró A, Fernández-Encinas A, Abad C, Amengual M, Prada E, et al. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology 2013; 1: 715–722.
[33] Han Zh, Yan Q, Ge W, Liu ZG, Gurunathan S, De Felici M, et al. Cytotoxic effects of ZnO nanoparticles on mouse testicular cells. Int J Nanomedicine 2016; 11: 5187–5203.
[34] Liu B, Wu SD, Shen LJ, Zhao TX, Wei Y, Tang XL, et al. Spermatogenesis dysfunction induced by PM2. 5 from automobile exhaust via the ROSmediated MAPK signaling pathway. Ecotoxicol Environ Saf 2019; 167: 161–168.
[35] Jia F, Sun Z, Yan X, Zhou B, Wang J. Effect of pubertal nano-TiO2 exposure on testosterone synthesis and spermatogenesis in mice. Arch Toxicol 2014; 88: 781–788.
[36] Boekelheide K, Fleming SL, Johnson KJ, Patel SR, Schoenfeld HA. Role of Sertoli cells in injury-associated testicular germ cell apoptosis. Proc Soc Exp Biol Med 2000; 225: 105–115.
[2] Powell JJ, Faria N, Thomas-McKay E, Pele LC. Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. J Autoimmun 2010; 34: J226–J233.
[3] Chaudhry Q, Scotter M, Blackburn J, Ross B, Boxall A, Castle L, et al. Applications and implications of nanotechnologies for the food sector. Food Addit Contam 2008; 25: 241–258.
[4] Peters RJB, van Bemmel G, Herrera-Rivera Z, Helsper HPFG, Marvin HJP, Weigel S, et al. Characterization of titanium dioxide nanoparticles in food products: Analytical methods to define nanoparticles. J Agric Food Chem 2014; 62: 6285–6293.
[5] Zhao L, Zhu Y, Chen Z, Xu H, Zhou J, Tang S, et al. Cardiopulmonary effects induced by occupational exposure to titanium dioxide nanoparticles. Nanotoxicology 2018; 12: 169–184.
[6] Wang R, Song B, Wu J, Zhang Y, Chen A, Shao L. Potential adverse effects of nanoparticles on the reproductive system. Int J Nanomedicine 2018; 13: 8487–8506.
[7] Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC. In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicol Sci 2005; 88: 412–419.
[8] Asare N, Instanes Ch, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, et al. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology 2012; 291: 65–72.
[9] 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. J Hazard Mater 2013; 258: 133–143.
[10] Lu Y, Luo B, Li J, Dai J. Perfluorooctanoic acid disrupts the blood-testis barrier and activates the TNFa/p38 MAPK signaling pathway in vivo and in vitro. Arch Toxicol 2016; 90: 971–983.
[11] Zhu Z, Kawai T, Umehara T, Hoque SM, Zeng W, Shimada M. Negative effects of ROS generated during linear sperm motility on gene expression and ATP generation in boar sperm mitochondria. Free Radic Biol Med 2019; 141: 159–171.
[12] Layali E, Tahmasbpour E, Jorsaraei SGhA. Effects of silver nanoparticles on lipid peroxidation and quality of sperm parameters in male rats. J Babol Univ Med Sci 2016; 18: 48–55.
[13] Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl 2014; 16: 31–38.
[14] 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 2014; 8: 654–662.
[15] 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. Euro J Exp Bio 2013; 3: 145–149.
[16] Ogunsuyi OM, Ogunsuyi OI, Akanni O, Alabi OA, Alimba CG, Adaramoye OA, et al. Alteration of sperm parameters and reproductive hormones in Swiss mice via oxidative stress after co-exposure to titanium dioxide and zinc oxide nanoparticles. Andrologia 2020; 52: e13758.
[17] Sabour M, Khoradmehr A, Kalantar SM, Danafar AH, Omidi M, Halvaei I, et al. Administration of high dose of methamphetamine has detrimental effects on sperm parameters and DNA integrity in mice. Int J Reprod Biomed 2017; 15: 161–168.
[18] Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME, et al. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report. Reprod Toxicol 1996; 10: 237–244.
[19] Nazar M, Talebi AR, Sharifabad MH, Abbasi A, Khoradmehr A, Danafar AH. Acute and chronic effects of gold nanoparticles on sperm parameters and chromatin structure in Mice. Int J Reprod Biomed 2016; 14: 637–642.
[20] Bahaodini A, Owjfard M, Tamadon A, Jafari SM. Low frequency electromagnetic fields long-term exposure effects on testicular histology, sperm quality and testosterone levels of male rats. Asian Pac J Reprod 2015; 4: 195–200.
[21] Panahi M, Keshavarz S, Rahmanifar F, Tamadon A, Mehrabani D, Karimaghai N, et al. Busulfan induced azoospermia: Stereological evaluation of testes in rat. Vet Res Forum 2015; 6: 273–278.
[22] Panahi M, Karimaghai N, Rahmanifar F, Tamadon A, Vahdati A, Mehrabani D, et al. Stereological evaluation of testes in busulfan-induced infertility of hamster. Comparat Clin Pathol 2015; 24: 1051– 1056.
[23] Khoradmehr A, Danafar AH, Halvaei I, Golzadeh J, Hosseini M, Mirjalili T, et al. Effect of prenatal methamphetamine administration during gestational days on mice. Iran J Reprod Med 2015; 13: 41–48.
[24] Bandegi L, Anvari M, Vakili M, Khoradmehr A, Mirjalili A, Talebi AR. Effects of antidepressants on parameters, melondiadehyde, and diphenyl-2- picryl-hydrazyl levels in mice spermatozoa. Int J Reprod Biomed 2018; 16: 365–372.
[25] Zeb A, Ullah F. A simple spectrophotometric method for the determination of thiobarbituric acid reactive substances in fried fast foods. J Anal Method Chem 2016; 2016: 9412767.
[26] Keramati Khiarak B, Karimipour M, Ahmadi A, Farjah GhH. Effects of oral administration of titanium dioxide particles on sperm parameters and in vitro fertilization potential in mice: A comparison between nano-and fine-sized particles. Vet Res Forum 2020; 11: 401–408.
[27] Sabeti P, Pourmasumi S, Rahiminia T, Akyash F, Talebi AR. Etiologies of sperm oxidative stress. Int J Reprod Biomed 2016; 14: 231–240.
[28] Lu T, Ling Ch, Hu M, Meng X, Deng Y, An H, et al. Effect of nano-titanium dioxide on bloodtestis barrier and MAPK signaling pathway in male mice. Biol Trace Elem Res 2021; 199: 2961–2971.
[29] Smith MA, Michael R, Aravindan RG, Dash S, Shah SI, Galileo DS, et al. Anatase titanium dioxide nanoparticles in mice: Evidence for induced structural and functional sperm defects after short-, but not long-, term exposure. Asian J Androl 2015; 17: 261–268.
[30] Morgan AM, Abd El-Hamid MI, Noshy PA. Reproductive toxicity investigation of titanium dioxide nanoparticles in male albino rats. World J Pharm Pharmaceut Sci 2015; 4: 34–49.
[31] 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. J Agric Food Chem 2015; 63: 7084–7092
[32] Ribas-Maynou J, García-Peiró A, Fernández-Encinas A, Abad C, Amengual M, Prada E, et al. Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay. Andrology 2013; 1: 715–722.
[33] Han Zh, Yan Q, Ge W, Liu ZG, Gurunathan S, De Felici M, et al. Cytotoxic effects of ZnO nanoparticles on mouse testicular cells. Int J Nanomedicine 2016; 11: 5187–5203.
[34] Liu B, Wu SD, Shen LJ, Zhao TX, Wei Y, Tang XL, et al. Spermatogenesis dysfunction induced by PM2. 5 from automobile exhaust via the ROSmediated MAPK signaling pathway. Ecotoxicol Environ Saf 2019; 167: 161–168.
[35] Jia F, Sun Z, Yan X, Zhou B, Wang J. Effect of pubertal nano-TiO2 exposure on testosterone synthesis and spermatogenesis in mice. Arch Toxicol 2014; 88: 781–788.
[36] Boekelheide K, Fleming SL, Johnson KJ, Patel SR, Schoenfeld HA. Role of Sertoli cells in injury-associated testicular germ cell apoptosis. Proc Soc Exp Biol Med 2000; 225: 105–115.