title: An evidence-based review of the genotoxic and reproductive effects of sulfur mustard.
abstract: Sulfur mustard (SM) is a chemical warfare agent which is cytotoxic in nature, and at the molecular level, SM acts as DNA alkylating agent leading to genotoxic and reproductive effects. Mostly, the exposed areas of the body are the main targets for SM; however, it also adversely affects various tissues of the body and ultimately exhibits long-term complications including genotoxic and reproductive effects, even in the next generations. The effect of SM on reproductive system is the reason behind male infertility. The chronic genotoxic and reproductive complications of SM have been observed in the next generation, such as reproductive hormones disturbances, testicular atrophy, deficiency of sperm cells, retarded growth of sperm and male infertility. SM exerts toxic effects through various mechanisms causing reproductive dysfunction. The key mechanisms include DNA alkylation, production of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide (NAD) depletion. However, the exact molecular mechanism of such long-term effects of SM is still unclear. In general, DNA damage, cell death and defects in the cell membrane are frequently observed in SM-exposed individuals. SM can activate various cellular and molecular mechanisms related to oxidative stress (OS) and inflammatory responses throughout the reproductive system, which can cause decreased spermatogenesis and impaired sperm quality via damage to tissue function and structure. Moreover, the toxic effects of SM on the reproductive system as well as the occurrence of male infertility among exposed war troopers in the late exposure phase is still uncertain. The chronic effects of SM exposure in parents can cause congenital defects in their children. In this review, we aimed to investigate chronic genotoxic and reproductive effects of SM and their molecular mechanisms in the next generations.
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Fazlullah
authors.initials: F
authors.lastname: Khan
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Kamal
authors.initials: K
authors.lastname: Niaz
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.|Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.
authors.forename: Fatima
authors.initials: F
authors.lastname: Ismail Hassan
authors.affiliation: International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran. Mohammad.Abdollahi@UToronto.Ca.|Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. Mohammad.Abdollahi@UToronto.Ca.|Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran. Mohammad.Abdollahi@UToronto.Ca.
authors.forename: Mohammad
authors.identifier: http://orcid.org/0000-0003-0123-1209
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000015:Abnormalities, Multiple / Q000139:chemically induced; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005837:Genitalia, Male / Q000187:drug effects; D006801:Humans; D007246:Infertility / Q000139:chemically induced*; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D018812:Paternal Exposure / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; D017382:Reactive Oxygen Species; D009151:Mustard Gas
keywords: Genotoxicity; Infertility; Sulfur mustard (SM)