title: Aryl hydrocarbon receptor-dependent induction of loss of mitochondrial membrane potential in epididydimal spermatozoa by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant known to exhibit toxic effects on the male reproductive system, including the epididymus and spermatozoa. However, the mechanism(s) that mediate dioxin toxicity in spermatozoa remain unclear. The aim of the present study was to investigate whether exposure to TCDD would cause a loss in mitochondrial membrane potential (Deltapsi(m)) in spermatozoa and whether such an effect is mediated by the Ah receptor (AhR). Exposure of C57BL/6 male mice to TCDD at concentrations of 0.1-50 microg/kg for 24 h caused a dose-dependent loss of Deltapsi(m) in epididymal spermatozoa compared to spermatozoa from vehicle-treated mice. However, this effect was not apparent in spermatozoa from AhR knockout (KO) mice. Exposure of spermatozoa from C57BL/6 mice to 1 nM or 5 nM TCDD in vitro also induced loss of Deltapsi(m). TCDD-exposed C57BL/6 mice failed to exhibit changes in the morphology of testes and epididymus, and did not show any increase in number of apoptotic germ cells. In addition, comparison of reactive oxygen species (ROS) production in spermatozoa from vehicle- and TCDD-treated mice indicated that exposure to TCDD resulted in elevated ROS levels in the spermatozoa from TCDD-treated mice. Moreover, blockade of ROS production by pretreatment with ROS scavenger N-acetylcysteine (NAC) mitigated the loss of Deltapsi(m) following TCDD exposure. Taken together, these data suggest that direct exposure of spermatozoa to TCDD triggers loss of Deltapsi(m) that is mediated by AhR-dependent production of ROS.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23113, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Fisher
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004822:Epididymis / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon