Cellular anomalies underlying retinoid-induced phocomelia

Reproductive Toxicology
Jian Zhou, D M Kochhar

Abstract

The question of how alterations in cell behavior produced by retinoic acid (RA) influenced the development of skeletogenic mesenchyme of the limb bud was examined in this study. Our established model was employed, which involves treatment of pregnant mice with a teratogenic dose of RA (100 mg/kg) on 11 days postcoitum (dpc) resulting in a severe truncation of all long bones of the forelimbs in virtually every exposed fetus. It is shown that RA, administered at a stage to induce phocomelia in virtually all exposed embryos, resulted in immediate appearance of enhanced cell death within the mesenchyme in the central core of the limb bud, an area destined for chondrogenesis. The central core mesenchyme, which in the untreated limb buds experiences a sharp decline in cell proliferation heralding the onset of chondrogenesis, demonstrated a reversal of the process; this mesenchyme maintained a higher rate of cell proliferation upon RA exposure. These events resulted in a truncation and disorganization of the chondrogenic anlage, more pronounced in zeugopodal mesenchyme than in the autopod. We conclude that an inhibition of chondrogenesis was secondary to a disruption in cellular behavior caused by RA, a likely consequence of misregula...Continue Reading

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Citations

Jun 12, 2010·Current Opinion in Genetics & Development·Rolf Zeller
Sep 16, 2010·Birth Defects Research. Part A, Clinical and Molecular Teratology·Tracie PennimpedeMartin Petkovich
Jun 27, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·Aimée ZunigaSimone Probst
May 31, 2016·Differentiation; Research in Biological Diversity·Aysel MammadovaJohannes W Von den Hoff
Sep 26, 2009·Toxicology Mechanisms and Methods·Yong-Sheng ZhongShi-Xin Du
Feb 10, 2010·Spinal Cord·P SekaranR K Senthil Kumar
Apr 17, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Min ZhangJoseph L Napoli
May 11, 2019·International Journal of Molecular Sciences·Maha El ShahawyAmel Gritli-Linde
Nov 18, 2020·Reproductive Toxicology·Thomas B KnudsenNancy C Baker

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