Transgenerational Genetic Effect of Trichloroethane (TCE) on Phenotypic Variation of Acrosomal Proteolytic Enzyme and Male Infertility Risk

Abstract

Exposure to trichloroethane (TCE), a ambiguous environmental toxicant, has been negatively associated with male reproductive performance. The objective was to investigate, in-vivo, the mutagenic, carcinogenic or teratogenic effect of TCE maternal exposure on sperm quality and testicular cytoarchitecture of F1 generation of mice. A motile sperm separation technique was used to estimate sperm motility and a gelatin slide technique was used to measure the number of the halo around the acrosome of individual sperm as an acrosomal proteolytic enzyme (APA). Animals were followed up for signs of toxicity and mortality. Alterations in testicular tissues have been histopathology investigated. No adverse signs, symptoms and mortality were observed in the animals treated with TCE. Moreover, significant changes were seen in body and testis weight. Results of semen analysis revealed that TCE lead to low sperm count, abnormal sperm morphology, and frequently of sperm motility. These results were correlated with decrease in APA when pre-leptotene or spermatogonial cells were tested, indicating a transgenerational toxic effects. Histopathological examination revealed that TCE insult marked alterations in the microstructures of testicular tissues appeared as severe morphological abnormal spermatozoa and vacuoles. Taken together, these results suggest that early exposure to TCE causes testicular toxicity and poor semen quality. The sperm phenotypes utilized in this study may increase the value of sperm for detection mutagenic developmentally active agents, and agent with anti-fertility effects in mammals. This in-vivo animal model represents a unique platform for assessing human reproductive toxicity potential and genetic risk of various environmental mutagens, carcinogens and teratogens in a rapid, efficient, and unbiased format.

Environmentally toxicant exposures induced intragenerational transmission of liver abnormalities in mice

“…Many studies reported that exposure to environmental insults may promote the transition of abnormal phenotypes between generations (Jones et al, 1996;Anway et al, 2005). The results of this study support our findings from previous studies in mice (Al-Griw et al, 2015b) by examining a variety of different abnormalities states in four-month-old male mice and characterizing the transgenerational changes in the F1 generation sperms (Al-Griw et al, 2015a). Early exposure to TCE reduces fertility and negatively affects pregnancy outcomes across multiple generations (AlGriw et al, 2015c).…”

“…Experimental studies in rodents indicate that exposure to environmental toxic substances during intrauterine life, postnatal life, early life, and/or germ cell exposures play a significant role in determining the mature phenotype and susceptibility to diseases in later life (Skinner et al, 2010(Skinner et al, , 2013. Epigenetic abnormalities/diseases in humans have been documented for reproductive tract abnormalities, brain and behavior abnormalities, immune system abnormalities (Anway et al, 2006a;Crews et al, 2007) as well as kidney (Anway et al, 2006b), ovarian, testis and prostate diseases (Salian et al, 2009;Nilsson et al, 2012;Al-Griw et al, 2015a). A number of environmental factors have been shown to induce transgenerational inheritance of adult onset disease and phenotypic variations (Skinner et al, 2010).…”

“…The current study was designed to investigate the transgenerational actions of a specific environmental toxicant trichloroethane (TCE), an industrial solvent and a degreasing agent, to induce alteration in a somatic cell integrity that correlates to the induction of abnormality in the hepatic tissue. Recently, it has been reported that TCE exposure environmentally (Al-Griw et al, 2015a, 2015c, 2016 or occupationally (Bruckner et al, 2001) on a daily basis is associated with increased risk of infertility, low fetal weight and early neonatal neurobehavioral abnormalities (Al-Griw et al, 2015b), as well as autoimmunity (Wang et al, 2013). Epigenetic inheritance has been studied extensively in the germ line through in utero exposure (Skinner, 2007;Manikkam et al, 2012;Skinner et al, 2013).…”

Oxidative Stress Mediated Cytotoxicity of Trichloroethane in a Model of Murine Splenic Injury

“…To evaluate the role of lipid peroxidation in TCE-induced toxicity, the serum levels of MDA in mice treated with TCE were determined (Figure 4). Lipid peroxidation (malondialdehyde; MDA) is a marker of oxidative lipid damage and a major oxidative product of peroxidized polyunsaturated fatty acids [19]. The results showed that serum MDA levels were significantly increased in the TCE-treated mice when compared with those in controls, with the highest levels recorded in the 400 µg/kg TCE-treated mice ( Figure 4A).…”

“…Then, 4 ml n-butanol was added, and the solution was centrifuged, cooled and the absorption of supernatant was obtained using spectrophotometer at 532 nm. The calibration curve was obtained using different concentrations of 1, 1, 3, 3-tetramethoxypropane as standard to determine the concentration of TBARS in samples as nmol/ml [18][19].…”