Related Experiment Video
Updated: Nov 8, 2025
Isolation of Sertoli Cells and Peritubular Cells from Rat Testes
Published on: February 8, 2016
Nano-TiO₂ Reduces Testosterone Production in Primary Cultured Leydig Cells from Rat Testis Through the Cyclic
Abstract:
Nano-titanium dioxide (nano-TiO₂) has been shown to inhibit testosterone synthesis in male mice or rats; however, the mechanisms underlying these effects have yet to be elucidated. In this study, we investigated whether the inhibition of testosterone synthesis by nano-TiO₂ on Leydig cells (LCs) was related to the dysfunction of the cAMP/CGMP/EGFR/MMP signaling pathway in primary cultures of LCs prepared from rat testis exposed to nano-TiO₂. We found that the early apoptotic rate of LCs increased by 4.34 and 4.94 times, respectively, after exposure to 20 g/mL and 40 g/mL nano-TiO₂ ; we also found that NO increased by 1.1 and 2.86 times, respectively. ROS increased by times of 0.71, 3.15 and 3.43; RNS increased by 0.62, 1.34 and 1.14 times; and SOD activity decreased by 18.3%, 28.16%, and 67.6%, respectively, when the concentration of nano-TiO₂ was 10, 20 and 40 g/mL. These results indicated that nano-TiO₂ treatment resulted caused damage to the LCs, including an imbalance of oxidation and antioxidation. Following nano-TiO₂ treatment, the cAMP content had decreased by 48%, 48% and 47.6%; cGMP content had decreased by 18.7%, 52.2% and 56.7%; the levels of ATP in the LCs had decreased by 15.15%, 45.75% and 66.67%; the expression of HCGR protein had decreased by 26.7%, 45.07% and 74.64%; the expression of LHR protein had decreased by 18.3%, 28.16% and 67.6%; and the levels of T had decreased by 34.48%, 46.62% and 44.12%. Collectively, our results indicated that the inhibition of testosterone production by nano-TiO₂ is related to the dysfunction of the cAMP/CGMP/EGFR/MMP signaling pathway.
Insights
Nano-titanium dioxide (nano-TiO₂) exposure damages rat Leydig cells, increasing apoptosis and oxidative stress. This disruption impairs testosterone synthesis by affecting the cAMP/cGMP/EGFR/MMP signaling pathway.
Area of Science:
- Toxicology
- Reproductive Biology
- Nanotechnology
Background:
- Nano-titanium dioxide (nano-TiO₂) is known to inhibit testosterone synthesis.
- The precise mechanisms behind nano-TiO₂-induced reproductive toxicity remain unclear.
- Leydig cells (LCs) are crucial for testosterone production.
Purpose of the Study:
- To investigate the impact of nano-TiO₂ on Leydig cell function.
- To determine if nano-TiO₂ affects the cAMP/cGMP/EGFR/MMP signaling pathway in LCs.
- To elucidate the mechanisms of nano-TiO₂-induced inhibition of testosterone synthesis.
Main Methods:
- Primary cultures of rat Leydig cells were exposed to varying concentrations of nano-TiO₂.
- Apoptosis rates, nitric oxide (NO), reactive oxygen species (ROS), reactive nitrogen species (RNS), and superoxide dismutase (SOD) activity were measured.
- Levels of cAMP, cGMP, ATP, and key proteins (HCGR, LHR) were quantified.
- Testosterone (T) levels were measured to assess synthesis inhibition.
Main Results:
- Nano-TiO₂ exposure significantly increased Leydig cell apoptosis and oxidative stress (elevated ROS/RNS, decreased SOD activity).
- Exposure led to decreased levels of cAMP, cGMP, ATP, HCGR, LHR, and ultimately, testosterone.
- A dose-dependent relationship was observed between nano-TiO₂ concentration and the observed toxic effects.
Conclusions:
- Nano-TiO₂ induces damage to rat Leydig cells, causing oxidative stress and apoptosis.
- The inhibition of testosterone synthesis by nano-TiO₂ is linked to the dysfunction of the cAMP/cGMP/EGFR/MMP signaling pathway.
- These findings highlight the potential reproductive risks associated with nano-TiO₂ exposure.
