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Title: Effects of retinoic acid upon pregastrulation mouse embryos

Abstract

The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, we treated pregnant mice with trans-retinoic acid (RA), a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. RA induced a novel set of malformations, such as supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period 4.5 to 5.5 days postmating. Other malformations were induced by RA treatments at later stages of development. The limb and lower-body duplications suggest that exongenous RA may influence not only the pattern for the hindlimbs, but that for the entire lower-body. If, indeed, the conceptus were affected in the late blastocyst and proamniotic-embryo stages, the possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation.

Authors:
 [1];  [2];  [3];  [4]
  1. National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)
  2. Oak Ridge National Laboratory, TN (United States)
  3. Univ. of Washington School of Medicine, Seattle, WA (United States)
  4. Children`s Hospital and Univ. of Washington, Seattle, WA (United States)
Publication Date:
OSTI Identifier:
89568
Report Number(s):
CONF-9405324-
Journal ID: EMMUEG; ISSN 0893-6692; TRN: 95:004220-0002
Resource Type:
Journal Article
Resource Relation:
Journal Name: Environmental and Molecular Mutagenesis; Journal Volume: 23; Journal Issue: Suppl.23; Conference: 25. annual meeting of the Environmental Mutagen Society, Portland, OR (United States), 7-12 May 1994; Other Information: PBD: 1994
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; RETINOIC ACID; BIOLOGICAL EFFECTS; EMBRYOS; MALFORMATIONS; MICE

Citation Formats

Bishop, J.B., Generoso, W.M., Polifka, J.E., and Rutledge, J.C. Effects of retinoic acid upon pregastrulation mouse embryos. United States: N. p., 1994. Web.
Bishop, J.B., Generoso, W.M., Polifka, J.E., & Rutledge, J.C. Effects of retinoic acid upon pregastrulation mouse embryos. United States.
Bishop, J.B., Generoso, W.M., Polifka, J.E., and Rutledge, J.C. 1994. "Effects of retinoic acid upon pregastrulation mouse embryos". United States. doi:.
@article{osti_89568,
title = {Effects of retinoic acid upon pregastrulation mouse embryos},
author = {Bishop, J.B. and Generoso, W.M. and Polifka, J.E. and Rutledge, J.C.},
abstractNote = {The zygote and subsequent preimplantation stages of early mammalian development are susceptible to certain chemical perturbations that cause abnormal development of the conceptus. In certain cases, disruption in patterns of gene expression could be a primary event leading to abnormal development. To investigate this hypothesis, we treated pregnant mice with trans-retinoic acid (RA), a known modulator of gene expression. Treatments were administered at various times during pregastrulation stages and the presumed onset of gastrulation. RA induced a novel set of malformations, such as supernumerary and ectopic limbs and duplication of portions of the lower body, but only when administered during the period 4.5 to 5.5 days postmating. Other malformations were induced by RA treatments at later stages of development. The limb and lower-body duplications suggest that exongenous RA may influence not only the pattern for the hindlimbs, but that for the entire lower-body. If, indeed, the conceptus were affected in the late blastocyst and proamniotic-embryo stages, the possibility arises that aspects of pattern formation of limbs and lower body actually occur prior to gastrulation.},
doi = {},
journal = {Environmental and Molecular Mutagenesis},
number = Suppl.23,
volume = 23,
place = {United States},
year = 1994,
month =
}
  • Experimental carcinogenesis has led to a concept that defines two discrete stages in the development of skin tumors: (i) initiation, which is accomplished by using a mutagen that presumably activates a protooncogene, and (ii) promotion, which is a reversible process brought about most commonly by repeated application of phorbol esters. The authors created a trangenic mouse strain that carries the activated v-Ha-ras oncogene fused to the promoter of the mouse embryonic {alpha}-like, {zeta}-globin gene. Unexpectedly, these animals developed papillomas at areas of epidermal abrasion and, because abrasion can also serve as a tumor-promoting event in mutagen-treated mouse skin, we testedmore » these mice for their ability to respond to phorbol ester application. Within 6 weeks virtually all treated carrier mice had developed multiple papillomas, some of which went on to develop squamous cell carcinomas and, more frequently, underlying sarcomas. They conclude that the oncogene preinitiates carrier mice, replacing the initiation/mutagenesis step and immediately sensitizing them to the action of tumor promoters. In addition, treatment of the mice with retinoic acid dramatically delays, reduces, and often completely inhibits the appearance of promoter-induced papillomas. This strain has use in screening tumor promoters and for assessing antitumor and antiproliferative agents.« less
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