Document Detail

Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse.
MedLine Citation:
PMID:  10036219     Owner:  NLM     Status:  MEDLINE    
The aryl hydrocarbon receptor (AHR) is a transcriptional regulatory protein that binds to upstream DNA response elements of target genes. Activation of the AHR by binding of ligands such as polyhalogenated dioxins, furans, and PCBs is associated with a wide range of adverse biological outcomes, including cancer, immune deficiencies, embryo/fetotoxicity, and reproductive toxicity. Investigations of the diverse biological responses mediated by the AHR led to production of a transgenic mouse in which the gene coding for the AhR was inactivated. AHR-deficient mice were fertile and at maturity exhibited immune system impairment and hepatic fibrosis. Our laboratory received several of these homozygous knockout (-/-) mice and mated them with wild-type (+/+) C57BL/6N mice to generate large numbers of heterozygotes (+/-). The -/- males were then mated with a total of 45 heterozygous +/- females. Offspring of these matings were genotyped and mated in all genotypic combinations. Although male and female -/- adults were fertile, the -/- females had difficulty maintaining conceptuses during pregnancy, surviving pregnancy and lactation, and rearing pups to weaning. Only 46% of the 39 pregnant -/- females successfully raised pups to weaning. The -/- pups showed poor survival during lactation (average death rate per litter was 16%) and after weaning (26.5% of the 230 weaned -/- pups died within 2 weeks). Only 39% of the implantations in uteri of -/- dams resulted in offspring surviving to Postnatal Day 45. Across all litters the sex ratios and genotypic frequencies were comparable to expected values. Reproductive success was adversely affected in Ahr-null females and conceptuses. Additional study is needed to reveal the etiology of these effects.
B D Abbott; J E Schmid; J A Pitt; A R Buckalew; C R Wood; G A Held; J J Diliberto
Related Documents :
15084019 - Effects of mating behaviour and the ovarian follicular state of female alpacas on conce...
18721809 - The effects of maternal corticosterone levels on offspring behavior in fast- and slow-g...
22685669 - Routine use of color doppler in fetal heart scanning in a low-risk population.
12116419 - Divergence and reticulation among montane populations of a jumping spider (habronattus ...
16603679 - Circadian rhythms in murine pups develop in absence of a functional maternal circadian ...
1787529 - Normal serum biochemical and hematological parameters in macaca fascicularis.
7137259 - Biologic activity and quantification of messenger rna coding for human chorionic somato...
2875959 - Andrological parameters in patients with varicocele and fertility disorders treated by ...
17007679 - Recovery and amplification of placental rna from dried maternal blood spots: utility fo...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  155     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-16     Completed Date:  1999-03-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  62-70     Citation Subset:  IM    
Reproductive Toxicology Division, National Health Effects and Environmental Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Embryo Implantation
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Aryl Hydrocarbon / deficiency*,  physiology
Reg. No./Substance:
0/Receptors, Aryl Hydrocarbon

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

Previous Document:  Suppression of calcium oscillation by tri-n-butyltin chloride in cultured rat hepatocytes.
Next Document:  The AH receptor and a novel gene determine acute toxic responses to TCDD: segregation of the resista...