3.5.3 Embryogenesis Both retinoic acid and retinol are essential for embryonic development, however, retinoic acid does not seem to be involved in vertebrate embryogenesis before gastrulation. After gastrulation specific genes of the Hox family are expressed in a wave starting about 7.5 days postcoitus in the mouse. The presence of retinoids together with their binding proteins and receptors in a temporally precise manner provides strong circumstantial evidence that retinoic acid-activated RARs regu late Hox gene expression(Ross, 1999). The Hox family consists of 38 genes arranged in four chromosomal clusters, which code for transcription factors that regulate development along the posterior axis. Retinoic acid is also thought to act in limb development and formation of the heart, eyes and ears. Experimental VAD has demonstrated that major target tissues of retinoic acid include the heart, central nervous system and structures derived from it, the circulatory, urogenital and respiratory systems and the development of skull, skeleton and limbs. Home ostasis of retinoic acid is maintained by enzyme systems, which are develop- mentally regulated by vitamin A. Inadequate vitamin A nutrition during early pregnancy may account for some paediatric congenital abnormalities(zile, 2001) However, the study of this aspect of vitamin A is in its ' infancy'and much more work is still to be done. A high incidence of spontaneous abortions and birth defects has been observed in the foetuses of women taking therapeutic doses of 13-cis retinoic acid. The drugs Accutane(13-cis retinoic acid) and etretinate, an aromatic analogue of all-trans retinoic acid have been most implicated in such effects(Armstrong et al, 1994). The dysmorphogenic effects caused by retinoids depend on dosage(exposure), the form of the retinoid, its rate of metabolism and tage of foetal development at the time the retinoid is taken. Retinoids are ter atogenic during the period of foetal organogenesis(first trimester)(Ross, 1999) 3.5.4 Immunity One of the first names for vitamin a was the anti-infective vitamin, which was based on the increased number of infections noted in VAd animals and humans (RoSs, 1996). In VAD the humoral response to bacterial, parasitic and viral infec- tions, cell-mediated immunity, mucosal immunity, natural killer cell activity and phagocytosis are all impaired. The primary immune response to protein antigens is markedly reduced but the response to bacterial lipopolysaccharides or the process of immunological memory essential for secondary response does not seem to be affected(Ross and Hammerling, 1994) A major site for vitamin A action in the immune response is the T-helper cell nd studies have shown that the activity of T-helper cells variety 1 (Thl)pre- cedes that of Th variety 2(Th2) and that vitamin A supports Th2 development (Cantorna et al, 1994). Hence, in the presence of VAd the ratio of Thl: Th2 may become elevated during an immune response. Retinol, probably in the form of 14-hydroxy-retroretinol(HRR), is thought to be involved in the proliferation of normal B-and T-cells, an action which can be modulated by some cytokines Retinoic acid, the usual active form of vitamin A, appears to be inactive in thes3.5.3 Embryogenesis Both retinoic acid and retinol are essential for embryonic development, however, retinoic acid does not seem to be involved in vertebrate embryogenesis before gastrulation. After gastrulation specific genes of the Hox family are expressed in a wave starting about 7.5 days postcoitus in the mouse. The presence of retinoids together with their binding proteins and receptors in a temporally precise manner provides strong circumstantial evidence that retinoic acid-activated RARs regu￾late Hox gene expression (Ross, 1999). The Hox family consists of 38 genes arranged in four chromosomal clusters, which code for transcription factors that regulate development along the posterior axis. Retinoic acid is also thought to act in limb development and formation of the heart, eyes and ears. Experimental VAD has demonstrated that major target tissues of retinoic acid include the heart, central nervous system and structures derived from it, the circulatory, urogenital and respiratory systems and the development of skull, skeleton and limbs. Home￾ostasis of retinoic acid is maintained by enzyme systems, which are develop￾mentally regulated by vitamin A. Inadequate vitamin A nutrition during early pregnancy may account for some paediatric congenital abnormalities (Zile, 2001). However, the study of this aspect of vitamin A is in its ‘infancy’ and much more work is still to be done. A high incidence of spontaneous abortions and birth defects has been observed in the foetuses of women taking therapeutic doses of 13-cis retinoic acid. The drugs Accutane (13-cis retinoic acid) and etretinate, an aromatic analogue of all-trans retinoic acid have been most implicated in such effects (Armstrong et al, 1994). The dysmorphogenic effects caused by retinoids depend on dosage (exposure), the form of the retinoid, its rate of metabolism and stage of foetal development at the time the retinoid is taken. Retinoids are ter￾atogenic during the period of foetal organogenesis (first trimester) (Ross, 1999). 3.5.4 Immunity One of the first names for vitamin A was ‘the anti-infective vitamin’, which was based on the increased number of infections noted in VAD animals and humans (Ross, 1996). In VAD the humoral response to bacterial, parasitic and viral infec￾tions, cell-mediated immunity, mucosal immunity, natural killer cell activity and phagocytosis are all impaired. The primary immune response to protein antigens is markedly reduced but the response to bacterial lipopolysaccharides or the process of immunological memory essential for secondary response does not seem to be affected (Ross and Hammerling, 1994). A major site for vitamin A action in the immune response is the T-helper cell and studies have shown that the activity of T-helper cells variety 1 (Th1) pre￾cedes that of Th variety 2 (Th2) and that vitamin A supports Th2 development (Cantorna et al, 1994). Hence, in the presence of VAD the ratio of Th1 :Th2 may become elevated during an immune response. Retinol, probably in the form of 14-hydroxy-retroretinol (HRR), is thought to be involved in the proliferation of normal B- and T-cells, an action which can be modulated by some cytokines. Retinoic acid, the usual active form of vitamin A, appears to be inactive in these Vitamins 41