title: The role of vitamin A in mammalian reproduction and embryonic development.
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.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. dame@biochem.wisc.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
authors.forename: Hector F
authors.initials: HF
authors.lastname: DeLuca
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D004032:Diet; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D023421:Models, Animal; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D050697:Retinal Dehydrogenase; D014801:Vitamin A / Q000502:physiology*; D014802:Vitamin A Deficiency / Q000503:physiopathology*
chemical_list: D018168:Receptors, Retinoic Acid; D014801:Vitamin A; D000445:Aldehyde Oxidoreductases; D050697:Retinal Dehydrogenase