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Fetal Alcohol Spectrum Disorder: Embryogenesis Under Reduced Retinoic Acid Signaling Conditions

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The Biochemistry of Retinoid Signaling III

Part of the book series: Subcellular Biochemistry ((SCBI,volume 95))

Abstract

Fetal Alcohol Spectrum Disorder (FASD) is a complex set of developmental malformations, neurobehavioral anomalies and mental disabilities induced by exposing human embryos to alcohol during fetal development. Several experimental models and a series of developmental and biochemical approaches have established a strong link between FASD and reduced retinoic acid (RA) signaling. RA signaling is involved in the regulation of numerous developmental decisions from patterning of the anterior–posterior axis, starting at gastrulation, to the differentiation of specific cell types within developing organs, to adult tissue homeostasis. Being such an important regulatory signal during embryonic development, mutations or environmental perturbations that affect the level, timing or location of the RA signal can induce multiple and severe developmental malformations. The evidence connecting human syndromes to reduced RA signaling is presented here and the resulting phenotypes are compared to FASD. Available data suggest that competition between ethanol clearance and RA biosynthesis is a major etiological component in FASD.

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Abbreviations

PAE:

Prenatal Alcohol Exposure

FAS:

Fetal Alcohol Syndrome

pFAS:

partial Fetal Alcohol Syndrome

FASD:

Fetal Alcohol Spectrum Disorder

IUGR:

Intrauterine Growth Restriction

ARND:

Alcohol-Related Neurodevelopmental Disorder

ARBD:

Alcohol-Related Birth Defects

CNS:

Central Nervous System

ADH:

Alcohol Dehydrogenase

ALDH:

Aldehyde Dehydrogenase

RALDH:

Retinaldehyde Dehydrogenase

SDR:

Short-chain Dehydrogenase/Reductase

DEAB:

4-Diethylaminobenzaldehyde

RA:

Retinoic Acid

RAR:

Retinoic Acid Receptor

RXR:

Retinoid X Receptor

RARE:

Retinoic Acid Responsive Element

RDH:

Retinol Dehydrogenase

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Authors and Affiliations

  1. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, POB 12271, 9112102, Jerusalem, Israel

    Abraham Fainsod, Liat Bendelac-Kapon & Yehuda Shabtai

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  1. Abraham Fainsod
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  2. Liat Bendelac-Kapon
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  3. Yehuda Shabtai
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Correspondence to Abraham Fainsod .

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  1. Maine Medical Center Research Institute, Scarborough, ME, USA

    Mary Ann Asson-Batres

  2. Département of Functional Génomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch, France

    Cecile Rochette-Egly

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Fainsod, A., Bendelac-Kapon, L., Shabtai, Y. (2020). Fetal Alcohol Spectrum Disorder: Embryogenesis Under Reduced Retinoic Acid Signaling Conditions. In: Asson-Batres, M., Rochette-Egly, C. (eds) The Biochemistry of Retinoid Signaling III. Subcellular Biochemistry, vol 95. Springer, Cham. https://doi.org/10.1007/978-3-030-42282-0_8

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