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纳米颗粒 TiO2 对睾酮生成的抑制与原代培养的大鼠睾丸间质细胞 ERK1/2-PKA-PKC 信号通路相关
Authors Li L, Mu X, Ye L, Ze Y, Hong F
Received 29 May 2018
Accepted for publication 14 August 2018
Published 28 September 2018 Volume 2018:13 Pages 5909—5924
DOI https://doi.org/10.2147/IJN.S175608
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
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.
Keywords: nanoparticulate titanium dioxide, primary cultured rat Leydig cells, mitochondrial injury, testosterone, ERK1/2–PKA–PKC signaling pathways