title: Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles.
abstract: Although numerous studies have described the accumulation of titanium dioxide nanoparticles (TiO(2) NPs) in the liver, kidneys, lung, spleen, and brain, and the corresponding damage, it is unclear whether or not TiO(2) NPs can be translocated to the ovary and cause ovarian injury, thus impairing fertility. In the current study, ovarian injury and gene-expressed characteristics in female mice induced by intragastric administration of TiO(2) NPs (10mg/kg) for 90 consecutive days were investigated. Our findings indicated that TiO(2) NPs can accumulate in the ovary and result in ovarian damage, cause an imbalance of mineral element distribution and sex hormones, decrease fertility or the pregnancy rate and oxidative stress in mice. Microarray analysis showed that in ovaries from mice treated with TiO(2) NPs compared to controls, 223 genes of known function were up-regulated, while 65 ovarian genes were down-regulated. The increased expression of Cyp17a1 following TiO(2) NPs treatment suggested that the increase in estradiol biosynthesis may be a consequence of increased TiO(2) NPs. In addition, the elevated expression of Akr1c18 implied that progesterone metabolism was accelerated, thus causing a decrease in the progesterone concentration. Taken together, the apparent regulation of key ovarian genes supports the hypothesis that TiO(2) NPs directly affects ovarian function.
authors.affiliation: Medical College, Soochow University, Suzhou 215123, People's Republic of China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Gao
authors.forename: Yuguan
authors.initials: Y
authors.lastname: Ze
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Sheng
authors.forename: Ringhu
authors.initials: R
authors.lastname: Hu
authors.forename: Suxin
authors.initials: S
authors.lastname: Gui
authors.forename: Xuezi
authors.initials: X
authors.lastname: Sang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cheng
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Tang
authors.forename: Fashui
authors.initials: F
authors.lastname: Hong
mesh_terms: D000818:Animals; D005260:Female; D005298:Fertility / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D046228:Microarray Analysis; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity*; D010049:Ovarian Diseases / Q000139:chemically induced* / Q000473:pathology; D010053:Ovary / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D014025:Titanium / Q000633:toxicity*
chemical_list: D012739:Gonadal Steroid Hormones; D010545:Peroxides; D017382:Reactive Oxygen Species; C009495:titanium dioxide; D014025:Titanium