title: Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice.
abstract: Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis-vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43-57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation.
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico.
authors.forename: Mayrut
authors.initials: M
authors.lastname: Urióstegui-Acosta
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hernández-Ochoa
authors.affiliation: Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Hidalgo, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Gutiérrez
authors.affiliation: Instituto Politécnico Nacional-UPIBI, D.F., Mexico.
authors.forename: Belem
authors.initials: B
authors.lastname: Piña-Guzmán
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Rafael-Vázquez
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico.
authors.forename: M J
authors.initials: MJ
authors.lastname: Solís-Heredia
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Martínez-Aguilar
authors.affiliation: Departamento de Toxicología, CINVESTAV-IPN, D.F., Mexico. Electronic address: mquintan@cinvestav.mx.
authors.forename: Betzabet
authors.initials: B
authors.lastname: Quintanilla-Vega
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D020101:Acrosome Reaction / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D020552:Comet Assay; D004261:DNA Replication / Q000187:drug effects*; D005260:Female; D005306:Fertilization / Q000187:drug effects; D066298:In Vitro Techniques; D007248:Infertility, Male / Q000139:chemically induced / Q000473:pathology; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D012098:Reproduction / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D007306:Insecticides; D009946:Organothiophosphorus Compounds; C014655:methamidophos; D000110:Acetylcholinesterase
keywords: DNA damage; Male fertility; Methamidophos; Organophosphate pesticides; Protein phosphorylation; Sperm function