Document Detail


Use of the fungicide carbendazim as a model compound to determine the impact of acute chemical exposure during oocyte maturation and fertilization on pregnancy outcome in the hamster.
MedLine Citation:
PMID:  1609414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Early pregnancy loss due to acute chemical exposure is difficult to detect and essentially impossible to characterize in humans. Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected as a model compound because it would be expected to perturb microtubule-dependent events occurring in the oocyte during meiotic maturation and fertilization. Such effects would likely lead to aneuploidy in the zygote with subsequent early pregnancy loss. Female hamsters were given a single oral dose of carbendazim during meiosis I (the afternoon of proestrus) prior to breeding, or during meiosis II (the morning of estrus) following overnight breeding. Pregnancy outcome was assessed on Day 15 (the afternoon before parturition). When given during during meiosis I, carbendazim treatment (750 or 1000 mg/kg body weight) significantly reduced the percentage of pregnant hamsters. In those animals that became pregnant, the average number of live pups was significantly lower at all dosages of carbendazim used (250, 500, 750, and 1000 mg/kg), an effect attributable to both preimplantation and early postimplantation losses. When given early on the morning of estrus, shortly before and during fertilization (0500 or 0600 hr), carbendazim treatment (1000 mg/kg) produced a similar decrease in litter size. This effect disappeared when carbendazim was administered at a slightly later time (0800 or 0900 hr), after the microtubule-dependent events of fertilization have occurred. These results demonstrate that a single exposure to a microtubule poison such as carbendazim at critical times, coincident with microtubule-dependent meiotic events, can result in very early pregnancy loss. Such loss was readily measurable in this animal model and serves as the basis for further mechanistic studies which would be impossible to conduct in humans.
Authors:
S D Perreault; S Jeffay; P Poss; J W Laskey
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  114     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1992 Jun 
Date Detail:
Created Date:  1992-07-23     Completed Date:  1992-07-23     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  225-31     Citation Subset:  IM    
Affiliation:
Reproductive Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
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MeSH Terms
Descriptor/Qualifier:
Abortion, Veterinary / chemically induced*
Animals
Benzimidazoles / toxicity*
Body Weight / drug effects
Carbamates*
Cricetinae
Dose-Response Relationship, Drug
Female
Fungicides, Industrial / toxicity*
Male
Meiosis / drug effects
Mesocricetus
Microtubules / drug effects,  physiology
Oocytes / drug effects*,  physiology
Pregnancy
Pregnancy, Animal / drug effects*
Time Factors
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Carbamates; 0/Fungicides, Industrial; H75J14AA89/carbendazim

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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