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Effects of retinoic acid on the neural crest-controlled organs of fetal rats

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Abstract.

Prenatal exposure of rat embryos to retinoic acid induces severe malformations involving various organs. The mechanisms of this embryopathy are known only in part. This study describes the malformations of the neural crest-derived organs in this model and shows that many of them fit into the pattern of disturbed neural crest organogenic control. Pregnant rats were exposed to either all-trans retinoic acid (125 mg/kg; n=17) or vehicle (n=10) on E10. Fetuses were recovered on E21 and external and internal malformations were sought. The craniofacial area, the trachea, parathyroids, thymus, thyroid, heart, great vessels, and adrenals were examined. In contrast with normal controls, 100% of retinoic acid animals had craniofacial, 94% anorectal, 90% limb, and 55% neural tube defects. The thymus was absent or ectopic in 76%, the parathyroids were absent or single in 88%, and the thyroid was abnormal in 41%. There were neural crest-type (outflow tract and/or pharyngeal aortic arch defects) cardiovascular malformations in 90% and the adrenals were absent in 52%. Interestingly, 9 of 11 (88%) animals with neural tube defects had absent adrenal glands. This association was significant (p<0.01) by Fisher exact test. Among the complex mechanisms of retinoic acid teratogenesis, severe disturbances of the neural crest pathway play a leading role. The simultaneous development of neural tube defects and adrenal agenesis suggests common pathogenic pathways.

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Acknowledgements. This work was supported in part by grant nos. 99/003-01, 01/0532 FIS, and 02/1220 (Fondo de Investigación Sanitaria), and a research fellowship from the Universidad Autonoma de Madrid and AECI.

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Authors and Affiliations

  1. Department of Surgery, Hospital Infantil Universitario "La Paz", 28046, Madrid, Spain

    Leopoldo Martinez, Juan A. Diez-Pardo & Juan A. Tovar

  2. Research Laboratory, Hospital Infantil Universitario "La Paz", 28046, Madrid, Spain

    Jiakang Yu & Salome Gonzalez

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  1. Jiakang Yu
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  2. Salome Gonzalez
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  3. Leopoldo Martinez
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  4. Juan A. Diez-Pardo
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  5. Juan A. Tovar
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Correspondence to Juan A. Tovar.

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Yu, J., Gonzalez, S., Martinez, L. et al. Effects of retinoic acid on the neural crest-controlled organs of fetal rats. Ped Surgery Int 19, 355–358 (2003). https://doi.org/10.1007/s00383-003-1010-9

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  • DOI: https://doi.org/10.1007/s00383-003-1010-9

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