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Suppression of testosterone production by nanoparticulate TiO2 is associated with ERK1/2-PKA-PKC signaling pathways in rat primary cultured Leydig cells
- Source :
- International Journal of Nanomedicine. 13:5909-5924
- Publication Year :
- 2018
- Publisher :
- Informa UK Limited, 2018.
-
Abstract
- Background Nanoparticulate titanium dioxide (nano-TiO2) enters the body through various routes and causes organ damage. Exposure to nano-TiO2 is reported to cause testicular injury in mice or rats and decrease testosterone synthesis, sperm number, and motility. Importantly, nano-TiO2 suppresses testosterone production by Leydig cells (LCs) and impairs the reproductive capacity of animals. Methods In an attempt to establish the molecular mechanisms underlying the inhibitory effect of nano-TiO2 on testosterone synthesis, primary cultured rat LCs were exposed to varying concentrations of nano-TiO2 (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. Results The data show that nano-TiO2 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-TiO2 concentration, nano-TiO2 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. Conclusion Our collective findings indicated that nano-TiO2-mediated suppression of testosterone in LCs was associated with regulation of ERK1/2-PKA-PKC signaling pathways.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cell signaling
Chemistry
Cholesterol side-chain cleavage enzyme
Organic Chemistry
Biophysics
Pharmaceutical Science
Motility
Bioengineering
General Medicine
Sperm
Biomaterials
03 medical and health sciences
030104 developmental biology
Endocrinology
Vacuolization
Internal medicine
Drug Discovery
medicine
Signal transduction
Protein kinase C
Testosterone
Subjects
Details
- ISSN :
- 11782013
- Volume :
- 13
- Database :
- OpenAIRE
- Journal :
- International Journal of Nanomedicine
- Accession number :
- edsair.doi...........402fe36a31b53c349d5a1ef927dc7b1b