Vitamin A and the developing embryo
- MRC Centre for Developmental Neurobiology
- 4th Floor New Hunt's House
- King's College London
- Guy's Campus, London Bridge
- London SE1 9RT, UK
- malcolm.maden@kcl.ac.uk
It was just before the First World War when vitamin A was chemically identified as “fat soluble A” and in the 1920s studies were conducted on laboratory rats to see what happened when this component was left out of the diet.1 A now familiar series of hypovitaminosis A changes occurred—widespread keratinisation of epithelia, decreased immune function, anaemia, xerophthalmia, and blindness. In the human population even subclinical deficiency of vitamin A leads to high levels of childhood morbidity and mortality. Astonishingly the ancient Egyptians knew that liver in the diet or the juice of cooked liver put into the eyes cured night blindness, but it took us about 5000 years to rediscover this medical fact.
Vitamin A deficiency and the embryo
Soon after, in the 1930s, similar dietary deprivation studies were performed with a view to asking what happens to the embryo when vitamin A is removed. In fact vitamin deficiencies, and most dramatically deficiencies of vitamin A, were the first dietary means of producing congenital malformations of the embryo. Most of these experiments were done with farm animals and the first report of this type of experiment was that a litter of pigs were born with no eyes at all.2Subsequently it was shown that a wide range of embryonic defects were apparent in the vitamin A deficient embryos of sheep, cattle, rabbits, rats, and humans.3 These defects include the central nervous system (hydrocephalus, spina bifida), eyes (anophthalmia, microphthalmia), face (harelip, cleft palate), dentition, ear (accessory ears, otosclerosis) limb, urinogenital system (cryptorchidism, ectopic ovaries, pseudohermaphrotisism, renal defects), skin (subcutaneous cysts), lungs (hypoplasia), and heart (incomplete ventricular septation, spongy myocardium, aortic arch defects, aorticopulmonary septal defects, valvulus communis). Clearly, the developing embryo crucially requires vitamin A for the proper development of a whole range of its organ systems.
Vitamin A excess and the embryo
It was not long after these …
