Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice.

Recent studies have demonstrated nanosized titanium dioxide (nano-TiO2)-induced fertility reduction and ovary injury in animals. To better understand how nano-TiO2 act in mice, female mice were exposed to 2.5, 5, and 10 mg/kg nano-TiO2 by intragastric administration for 90 consecutive days; the ovary injuries, fertility, hormone levels, and inflammation-related or follicular atresia-related cytokine expression were investigated. The results showed that nano-TiO2 was deposited in the ovary, resulting in significant reduction of body weight, relative weight of ovary and fertility, alterations of hematological and serum parameters and sex hormone levels, atretic follicle increases, inflammation, and necrosis. Furthermore, nano-TiO2 exposure resulted in marked increases of insulin-like growth factor-binding protein 2, epidermal growth factor, tumor necrosis factor-α, tissue plasminogen activator, interleukin-1β, interleukin -6, Fas, and FasL expression, and significant decreases of insulin-like growth factor-1, luteinizing hormone receptor, inhibin α, and growth differentiation factor 9 expression in mouse ovary. These findings implied that fertility reduction and ovary injury of mice following exposure to nano-TiO2 may be associated with alteration of inflammation-related or follicular atresia-related cytokine expressions, and humans should take great caution when handling nano-TiO2

Effects of TiO₂ NPs on mRNA expressions of inflammatory cytokines in mouse hippocampus caused by nasal administration of TiO₂ NPs for 90 consecutive days.

<p>*p < 0.05, **p<0.01, and ***p<0.01. Values represent means ± SD (<i>N</i>  = 5).</p

Effects of TiO₂ NPs on protein expressions of inflammatory cytokines in mouse hippocampus caused by nasal administration of TiO₂ NPs for 90 consecutive days.

<p>*p < 0.05, **p<0.01, and ***p<0.01. Values represent means ± SD (<i>N</i>  = 5).</p

Hydrodynamic diameter distribution of TiO₂ NPs in HPMC using DLS characterization.

<p>Hydrodynamic diameter distribution of TiO₂ NPs in HPMC using DLS characterization.</p

The content of titanium in mouse hippocampus following nasal administration of TiO₂ NPs for 90 consecutive days.

<p>Bars marked with three asterisks means it is significantly different from the control (unexposed mice) at the 0.1% confidence level, respectively. Values represent means ± SD (<i>N</i>  = 5).</p

Effects of TiO₂ NPs on locomotor activity in mice in the Y-maze after nasal administration of TiO₂ NPs for 90 consecutive days.

<p>Bars marked with an asterisk, double asterisks or three asterisks means it is significantly different from the control (unexposed mice) at the 5, 1, and 0.1% confidence level, respectively. Values represent means ± D (<i>N</i> = 10).</p

The (101) X-ray diffraction peak of anatase TiO₂ NPs.

<p>The (101) X-ray diffraction peak of anatase TiO₂ NPs.</p

Effect of TiO₂ NPs on spatial recognition memory in mice in the Y-maze after nasal administration of TiO₂ NPs for 90 consecutive days.

<p>Bars marked with an asterisk, double asterisks or three asterisks means it is significantly different from the control (unexposed mice) at the 5, 1, and 0.1% confidence level, respectively. Values represent means ± D (<i>N</i> = 10).</p