THE ROLE OF VITAMIN A IN MAMMALIAN REPRODUCTION AND EMBRYONIC DEVELOPMENT

Abstract

▪ 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.