title: Anatase titanium dioxide nanoparticles in mice: evidence for induced structural and functional sperm defects after short-, but not long-, term exposure.
abstract: Titanium dioxide (TiO 2 ) nanoparticles (TNPs) are widely used commercially and exist in a variety of products. To determine if anatase TNPs (ATNPs) in doses smaller than previously used reach the scrotum after entry in the body at a distant location and induce sperm defects, 100% ATNP (2.5 or 5 mg kg-1 body weight) was administered intraperitoneally to adult males for three consecutive days, followed by sacrifice 1, 2, 3, or 5 weeks later (long-) or 24, 48 or 120 h (short-term exposure). Transmission electron microscopy revealed the presence of ANTP in scrotal adipose tissues collected 120 h postinjection when cytokine evaluation showed an inflammatory response in epididymal tissues and fluid. At 120 h and up to 3 weeks postinjection, testicular histology revealed enlarged interstitial spaces. Significantly increased numbers of terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling-positive (apoptotic) germ (P = 0.002) and interstitial space cells (P = 0.04) were detected in treated males. Caudal epididymal sperm from the short-term, but not a long-term, arm showed significantly (P < 0.001) increased frequencies of flagellar abnormalities, excess residual cytoplasm (ERC), and unreacted acrosomes in treated versus controls (dose-response relationship). A novel correlation between ERC and unreacted acrosomes was uncovered. At 120 h, there were significant decreases in hyperactivated motility (P < 0.001) and mitochondrial membrane potential (P < 0.05), and increased reactive oxygen species levels (P < 0.00001) in treated versus control sperm. These results indicate that at 4-8 days postinjection, ANTP induce structural and functional sperm defects associated with infertility, and DNA damage via oxidative stress. Sperm defects were transient as they were not detected 10 days to 5 weeks postinjection.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Smith
authors.forename: Rowan
authors.initials: R
authors.lastname: Michael
authors.forename: Rolands G
authors.initials: RG
authors.lastname: Aravindan
authors.forename: Soma
authors.initials: S
authors.lastname: Dash
authors.forename: Syed I
authors.initials: SI
authors.lastname: Shah
authors.forename: Deni S
authors.initials: DS
authors.lastname: Galileo
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Martin-DeLeon
mesh_terms: D000177:Acrosome / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D000818:Animals; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005407:Flagella / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D023421:Models, Animal; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D014025:Titanium / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; C009495:titanium dioxide; D014025:Titanium