Adverse Reproductive Outcomes in the Transgenic Ah Receptor-Deficient Mouse
Abstract
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 Po…
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Only 46% of null females would successfully raise pups to weaning.
“Subsequent study revealed that only 46% of null females would successfully raise pups to weaning (Abbott et al., 1999).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Abbott et al., 1999
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Rodent Genetic Models of Ah Receptor Signaling
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“Subsequent study revealed that only 46% of null females would successfully raise pups to weaning (Abbott et al. 1999).”
Background
- Authors
- Abbott, B. D., Schmid, J. E., Pitt, J. A., Buckalew, A. R., Wood, C. R., Held, G. A., & Diliberto, J. J.
- Affiliations
- Environmental Protection Agency (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 155
- Issue
- 1
- Pages
- 62-70
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W1997013077
- Cited by
- 219
- References
- 0
- Citations by year
- 2026: 7 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 7 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 6 · 2013: 8 · 2012: 9
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology and Applied Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- aryl hydrocarbon receptor, AhR knockout mice, reproductive toxicity, miscarriage, pup survival, embryo-fetal toxicity, heterozygous females, transgenic mouse model
- MeSH terms
- Animals, Breeding, Female, Fertility, Male, Mice, Inbred C57BL, Mice, Transgenic, Embryo Implantation, Pregnancy, Reproduction, Receptors, Aryl Hydrocarbon, Mice
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