The role of vitamin A in mammalian reproduction and embryonic development

Annu Rev Nutr. 2002;22:347-81. doi: 10.1146/annurev.nutr.22.010402.102745E.

Abstract

Since the late 1980s, there has been an explosion of information on the molecular mechanisms and functions of vitamin A. This review focuses on the essential role of vitamin A in female reproduction and embryonic development and the metabolism of vitamin A (retinol) that results in these functions. Evidence strongly supports that in situ-generated all-trans retinoic acid (atRA) is the functional form of vitamin A in female reproduction and embryonic development. This is supported by the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency with atRA, the block in embryonic development that occurs in retinaldehyde dehydrogenase type 2 null mutant mice, and the essential roles of the retinoic acid receptors, at least in embryogenesis. Early studies of embryos from marginally vitamin A-deficient (VAD) pregnant rats revealed a collection of defects called the vitamin A-deficiency syndrome. The manipulation of all-trans retinoic acid (atRA) levels in the diet of VAD female rats undergoing a reproduction cycle has proved to be an important new tool in deciphering the points of atRA function in early embryos and has provided a means to generate large numbers of embryos at later stages of development with the vitamin A-deficiency syndrome. The essentiality of the retinoid receptors in mediating the activity of atRA is exemplified by the many compound null mutant embryos that now recapitulate both the original vitamin A-deficiency syndrome and exhibit a host of new defects, many of which can also be observed in the VAD-atRA-supported rat embryo model and in retinaldehyde dehydrogenase type 2 (RALDH2) mutant mice. A major task for the future is to elucidate the atRA-dependent pathways that are normally operational in vitamin A-sufficient animals and that are perturbed in deficiency, thus leading to the characteristic VAD phenotypes described above.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aldehyde Oxidoreductases / metabolism
  • Animals
  • Diet
  • Embryonic and Fetal Development / physiology*
  • Female
  • Humans
  • Mice
  • Models, Animal
  • Phenotype
  • Pregnancy
  • Rats
  • Receptors, Retinoic Acid / metabolism
  • Reproduction / physiology*
  • Retinal Dehydrogenase
  • Vitamin A / physiology*
  • Vitamin A Deficiency / physiopathology*

Substances

  • Receptors, Retinoic Acid
  • Vitamin A
  • Aldehyde Oxidoreductases
  • Retinal Dehydrogenase