Exposure to zinc oxide nanoparticles affects testicular structure, reproductive development and spermatogenesis in parental and offspring male rats

Abstract

Background: This study aimed to comprehensively evaluate the toxicity exerted by zinc oxide nanoparticles (ZnO NPs) on rat testis and its effects on fertility and progeny development.Methods: Different concentrations of ZnO NPs were administered by gavage to Sprague Dawley (SD) rats to examine the adverse effects resulting from pre-and post-natal exposure. Systemic distribution of ZnO NPs, developmental performance, sperm parameters, reproductive performance, histopathological examination, and sex hormone levels were determined scheduled in the experimental rats and their male offspring. The comparative in vitro cytotoxicity of the ZnO NPs was determined among C18-4, TM3, and TM4 cells. The toxicity exerted by ZnO NPs on germ cells in vitro and the effects on the expression of cytoskeleton and blood-testis barrier (BTB)-related proteins were also determined.Results: After oral gavage, ZnO NPs mainly accumulated in the liver and testes of rats; 350 mg/kg ZnO NPs adversely affected the epididymal weight, sperm motility, and hormone levels but did not affect the fertility of rats. In addition, 350 mg/kg ZnO NPs significantly reduced the reproductive and developmental performance of offspring male rats. Testicular histopathological and electron microscopic ultrastructure examinations showed more significant abnormal structural changes than those observed in parental rats. The results of in vitro cell experiments further showed that ZnO NPs exerted cytotoxic effects on germ cells, and led to DNA damage, nucleoskeleton and cytoskeleton alterations, and could regulate actin changes through changes in LC3B.Conclusions: It is possible that ZnO NPs act directly on TM4 cells by penetrating the BTB, causing damage to the cytoskeleton and disrupting the dynamic balance of the BTB, thereby destroying the microenvironment necessary for spermatogenesis, which may lead to poor reproduction in rats.

Investigation of the Effects of Metallic Nanoparticles on Fertility Outcomes and Endocrine Modification of the Hypothalamic-Pituitary-Gonadal Axis

“…Studies published after this meta-analysis point in the same direction, as is the case on impairments of the mitochondrial dynamics in mouse testis after five intravenous doses (spaced with 3 day intervals) of 5 mg/kg body weight of TiO 2 -and Ag-NPs [6]. In an extended one-generation reproductive toxicity study (which was not conducted according to OECD-TG guidelines), Hong and co-workers [7] reported that 350 mg/kg body weight of ZnO-NPs caused statistically significant reductions in conception and pregnancy rates, sperm survival and sperm count, presumably by disrupting the blood-testis barrier and destroying the microenvironment needed for spermatogenesis. Silver NPs were found able to interfere with spermatogenesis and oogenesis by negatively affecting meiosis in zebrafish gonads [8] and ZnO-NPs were also able to cause follicular developmental retardation, which alters oocyte ovulation and "reducing the fecundity of female zebrafish [9].…”

Alleviative Role of Hemin on Reproductive Functions of Adult Male Rats Treated with Copper Oxide Nanoparticles

“…The intact, normal epididymal environment that the absorptive and secretory characteristics of the epididymal lining epithelium offer is necessary for these sperm changes (Hinton and Cooper, 2010). There is insufficient information from animal experiments to support the possibility that the unique features of nanomaterials might be damaging to the testicles, despite prior in vitro and in vivo experiments showing this (Hong et al, 2022). Hence, utilizing biochemical methods and sperm analysis is required to assess the potential protective function of hemin against the damaging impacts of CuO NPs on the testis and epididymal sperm of adult albino rats.…”

Characterization, dose dependent assessment of hepatorenal oxidative stress, hematological parameters and histopathological divulging of the hepatic damages induced by Zinc oxide nanoparticles (ZnO-NPs) in adult male Sprague Dawley rats

“…Nanotechnology is the branch of science that deals with the production and development of nanomaterials which are less than 100 nm in size ( Hong et al 2022 ). Nanoparticles are being studied due to various distinct properties i.e., great surface area towards volume ratio, great surface adsorption capability and more reactiveness ( Doolotkeldieva et al 2022 ).…”