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Suppression of testosterone production by nanoparticulate TiO 2 is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2018 Sep 28; Vol. 13, pp. 5909-5924. Date of Electronic Publication: 2018 Sep 28 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Background: Nanoparticulate titanium dioxide (nano-TiO <subscript>2</subscript> ) enters the body through various routes and causes organ damage. Exposure to nano-TiO <subscript>2</subscript> is reported to cause testicular injury in mice or rats and decrease testosterone synthesis, sperm number, and motility. Importantly, nano-TiO <subscript>2</subscript> suppresses testosterone production by Leydig cells (LCs) and impairs the reproductive capacity of animals.<br />Methods: In an attempt to establish the molecular mechanisms underlying the inhibitory effect of nano-TiO <subscript>2</subscript> on testosterone synthesis, primary cultured rat LCs were exposed to varying concentrations of nano-TiO <subscript>2</subscript> (0, 10, 20, and 40 µg/mL) for 24 hours, and alterations in cell viability, cell injury, testosterone production, testosterone-related factors (StAR, 3βHSD, P450scc, SR-BI, and DAX1), and signaling molecules (ERK1/2, PKA, and PKC) were investigated.<br />Results: The data show that nano-TiO <subscript>2</subscript> crosses the membrane into the cytoplasm or nucleus, triggering cellular vacuolization and nuclear condensation. LC viability decreased in a time-dependent manner at the same nano-TiO <subscript>2</subscript> concentration, nano-TiO <subscript>2</subscript> treatment (10, 20, and 40 µg/mL) decreased MMP (36.13%, 45.26%, and 79.63%), testosterone levels (11.40% and 44.93%), StAR (14.7%, 44.11%, and 72.05%), 3βHSD (26.56%, 50%, and 79.69%), pERK1/2 (27.83%, 63.61%, and 78.89%), PKA (47.26%, 70.54%, and 85.61%), PKC (30%, 50%, and 71%), SR-BI (16.41%, 41.79%, and 67.16%), and P450scc (39.41%, 55.26%, and 86.84%), and upregulated DAX1 (1.31-, 1.63-, and 3.18-fold) in primary cultured rat LCs.<br />Conclusion: Our collective findings indicated that nano-TiO <subscript>2</subscript> -mediated suppression of testosterone in LCs was associated with regulation of ERK1/2-PKA-PKC signaling pathways.<br />Competing Interests: Disclosure The authors report no conflicts of interest in this work.
- Subjects :
- Animals
Cell Survival drug effects
Cells, Cultured
Endocytosis drug effects
Hydrodynamics
Leydig Cells drug effects
Leydig Cells ultrastructure
Male
Membrane Potential, Mitochondrial drug effects
Mice
Models, Biological
Nanoparticles ultrastructure
Rats
Testosterone metabolism
X-Ray Diffraction
Cyclic AMP-Dependent Protein Kinases metabolism
Leydig Cells metabolism
MAP Kinase Signaling System drug effects
Nanoparticles chemistry
Protein Kinase C metabolism
Testosterone biosynthesis
Titanium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 30319256
- Full Text :
- https://doi.org/10.2147/IJN.S175608