Vitamin A in Reproduction and Development 英文参考文献.docVIP

Nutrients 2011, 3, 385-428; doi:10.3390/nu3040385 OPEN ACCESS nutrients ISSN 2072-6643 /journal/nutrients Review Vitamin A in Reproduction and Development Margaret Clagett-Dame 1,2,* and Danielle Knutson 1 1 Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA; E-Mail: dcknutson@ 2 School of Pharmacy, Pharmaceutical Sciences Division, University of Wisconsin-Madison, 777 Highland Ave., Madison, WI 53705, USA * Author to whom correspondence should be addressed; E-Mail: dame@; Tel.: +1-608-262-3450; Fax: +1-608-262-7122. Received: 24 November 2010; in revised form: 28 February 2011 / Accepted: 22 March 2011 / Published: 29 March 2011 Abstract: The requirement for vitamin A in reproduction was first recognized in the early 1900’s, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of ca