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Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium
Guodong Gao1, Yuguan Ze, Bing Li
1Medical College, Soochow University, Suzhou 215123, People's Republic of China.
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.
Insights
Titanium dioxide nanoparticles (TiO(2) NPs) accumulate in the ovaries, causing damage and reduced fertility in female mice. This study reveals TiO(2) NPs directly impact ovarian function and hormone balance.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Nanomedicine
Background:
- Titanium dioxide nanoparticles (TiO(2) NPs) are widely studied for accumulation in organs like the liver and kidneys.
- The translocation and impact of TiO(2) NPs on ovarian function and female fertility remain largely uncharacterized.
Purpose of the Study:
- To investigate the effects of chronic oral exposure to TiO(2) NPs on ovarian injury and gene expression in female mice.
- To determine if TiO(2) NPs can accumulate in the ovary and impair reproductive health.
Main Methods:
- Female mice were administered TiO(2) NPs (10mg/kg) intragastrically for 90 days.
- Ovarian injury, mineral element distribution, sex hormone levels, fertility, and oxidative stress were assessed.
- Microarray analysis was employed to examine gene expression changes in the ovaries.
Main Results:
- TiO(2) NPs were found to accumulate in the ovaries, leading to ovarian damage and oxidative stress.
- Exposure to TiO(2) NPs caused an imbalance in mineral elements and sex hormones, decreasing fertility and pregnancy rates.
- Microarray analysis revealed significant alterations in ovarian gene expression, including increased Cyp17a1 and Akr1c18, suggesting impacts on estradiol and progesterone metabolism.
Conclusions:
- Chronic oral exposure to TiO(2) NPs can translocate to the ovary, causing direct damage and impairing reproductive function.
- The observed changes in gene expression highlight specific molecular pathways affected by TiO(2) NPs in the ovary.
- These findings suggest that TiO(2) NPs pose a potential risk to female fertility.
