Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress.
Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A(3) (CMA(3))-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA(3)-staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission.
Piña-Guzmán
B
B
Sección Externa de Toxicología, CINVESTAV, Av. IPN #2508, Col. Zacatenco, Mexico City, 07360, Mexico.
Solís-Heredia
M J
MJ
Rojas-García
A E
AE
Urióstegui-Acosta
M
M
Quintanilla-Vega
B
B
D000818:Animals; D021461:Animals, Outbred Strains; D017209:Apoptosis / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008743:Methyl Parathion / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009152:Mutagenicity Tests; D018384:Oxidative Stress / Q000187:drug effects*; D018812:Paternal Exposure; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002843:Chromatin; D007306:Insecticides; D008743:Methyl Parathion; D008315:Malondialdehyde