X-ray diffraction patterns were obtained at room temperature with diffractometry (Mercury Cambridge Crystallographic Data Centre, Cambridge, UK) using Ni-filtered CuK radiation. Mean particle size was determined by measuring more than 100 individual particles that were randomly sampled. In brief, suspended nano-TiO 2 particles were deposited onto carbon-film TEM grids and allowed to dry in air. Particle sizes of nano-TiO 2 suspended in DMEM-F12 were determined using transmission electron microscopy (TEM Tecnai G 2 Spirit FEI, Hillsboro, OR, USA) operating at 100 kV. 37, 38 Nano-TiO 2 powder was dispersed in DMEM and Ham’s F12 nutrient mixture (DMEM-F12 Sigma-Aldrich, St Louis, MO, USA) containing 10% PBS (Solarbio, Beijing, China), following which the suspensions (5 mg/L) were treated ultrasonically for 30 minutes and mechanically vibrated for 5 minutes. Nano-TiO 2 (anatase type, TiO 2 content >99.5%) was kindly provided by Professor Yang Ping (College of Chemistry, Soochow University, China) and characterized according to previous reports. We additionally examined the effects of nano-TiO 2 on expression of proteins involved in testosterone generation, including StAR, 3βHSD, P450scc, SR-BI, and DAX1, and signaling molecules, such as ERK1/2, pERK1/2, PKA, and PKC, and whether the ERK1/2–PKA–PKC pathways participate in nano-TiO 2-mediated impairment of testosterone generation in LCs. To examine this theory, rat primary cultured LCs were exposed to different concentrations of nano-TiO 2, and changes in mitochondrial membrane potential and testosterone secretion were detected to evaluate the effects on cell viability, ultrastructure, and function. Here, we hypothesized that inhibition of testosterone biosynthesis by nano-TiO 2 is achieved by regulation of testosterone-related factors through the ERK1/2–PKA–PKC signaling pathways in LCs. 31 – 36 Limited studies to date have focused on the molecular mechanisms underlying the effects of nano-TiO 2 on testosterone generation. 30 StAR modulates the transfer of cholesterol from the cytoplasm to mitochondria, regarded as the rate-limiting step in steroid-hormone synthesis. 29 ERK1/2 exerts stimulatory effects on steroidogenesis. Association of the MAPK–ERK signaling cascade with steroid biosynthesis is suggested through regulation of StAR expression via multiple pathways and factors in mouse LCs. 27 StAR plays an important role in testosterone synthesis, 28 and is regulated by ERK1/2. Cholestenone is metabolized to pregnenolone, and subsequently testosterone is generated through a reaction catalyzed by 3βHSD and 17βHSD. Testosterone synthesis is a complex process in which cholestenone is transferred from the cytoplasm to mitochondria via StAR, followed by acceleration of the cholesterol side-chain-cleavage process via the P450scc enzyme in LCs. 17 – 25 However, the mechanisms underlying the suppressive effects of nano-TiO 2 on testosterone production are yet to be established. 13 Nano-TiO 2 has additionally been shown to enter the testis through the blood–testis barrier and migrate to the testicular microenvironment composed of Sertoli cells, spermatids, and Leydig cells (LCs), 14 – 16 leading to inhibition of >90% testosterone production, spermatozoa degeneration, and consequent reduction in LCs and sperm number, sperm motility, and male fertility. 3, 9 – 12 We have reported nano-TiO 2 deposition in various organs of mice after exposure for 14 consecutive days in the following order: liver > kidney > spleen > lung > brain > heart.
#ZETASIZER NANO SERIES BASIC GUIDE SKIN#
1 – 6 Due to its widespread usage and specific physical and chemical properties, 7 nano-TiO 2 is transferred to the human body through various routes, including inhalation, environmental intake (food additives or packaging components), and biomedical applications (gastrointestinal absorption or skin exposure), 1, 6, 8 and subsequently travels through the blood circulation into the liver, brain, spleen, heart, kidneys, lungs, and ovaries. The compound has numerous applications in industry, coating systems, medicine, everyday lives, and the environment. Nanoparticulate titanium dioxide (nano-TiO 2) is characterized by a large surface-area ratio, strong mechanical properties, low melting point, and magnetism.
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