Vitamin A is necessary for support of growth, health, and life of higher animals. In the absence of vitamin A, animals will cease to grow and eventually die. The metabolic function of vitamin A, explained in biochemical terms, is still not completely understood. Vitamin A deficiency causes at least four different and probably physiologically distinct lesions: loss of vision due to a failure of rhodopsin formation in the retina; defects in bone growth; defects in reproduction (i.e., failure of spermatogenesis in the male and resorption of the fetus in the female); and defects in growth and differentiation of epithelial tissues, frequently resulting in keratinization.
More is known about the role of vitamin A in vision than any of its other functions. Retinol is utilized in the aldehyde form (all-trans-retinol to 11-cis-retinal) in the retina of the eye as the prosthetic group in rhodopsin for dim light vision (rods) and as the prosthetic group in iodopsin for bright light and color vision (cones). It has been found that retinoic acid, which is a form of vitamin A in the body, supports growth and tissue differentiation but not vision or reproduction (Scott et al., 1982). Vitamin A-deficient rats fed retinoic acid were healthy in every respect, with normal estrus and conception, but failed to give birth and resorbed their fetuses. When retinol was given even at a late stage in pregnancy, fetuses were saved. Male rats receiving retinoic acid were healthy but produced no sperm, and without vitamin A both sexes were blind (Anonymous, 1977). Hale (1935) documented the defects resulting from vitamin A deficiency in sows; they included pigs born blind and even with incomplete development of eye tissue. Watt and Barlow (1956) presented circumstantial evidence that vitamin A deficiency in sow and gilt diets led to blind piglets with microphthalmia.
Chew et al. (1982) and Brief and Chew (1985) suggested that beta-carotene plays a role independent of vitamin A in swine reproduction. Their research suggested that elevation of maternal plasma vitamin A or beta-carotene improves embryonic survival, possibly because more uterine-specific proteins are secreted. Talavera and Chew (1988) found that beta-carotene was more effective in stimulating progesterone secretion by pig corpus luteum in vitro than either retinol or retinoic acid. These earlier studies involved treatments using both injections and enhanced dietary levels. In a study involving over 600 sows, Coffey et al. (1989) found that injecting beta-carotene (0, 50, 100, or 200 mg) at the time of weaning linearly increased by approximately 14% the numbers of live-born pigs at the next farrowing. Coffey et al. (1990) determined that injection of beta-carotene is much more effective than oral supplementation with regard to the influence on plasma and tissue concentrations. Coffey and Britt (1991), reported improvements in the number of pigs born alive when equivalent doses of vitamin A were utilized, confirming the positive effects of vitamin A on reproductive performance. Treatments consisted of injections of 200 mg beta-carotene, 50,000 IU vitamin A (palmitate) or vehicle (control) at weaning, breeding and day seven after breeding. In a subsequent report, Coffey and Britt (1993) provided additional evidence that litter size could be enhanced by the injection of either beta-carotene or vitamin A to sows receiving sufficient quantities of dietary vitamin A. Whaley et al. (1997) presented data leading them to conclude that retinol palmitate treatment may influence the follicular environment and thus would synchronize resumption of meiosis and enhance early embryonic survival in pigs. In this study, retinol palmitate (1 million IU) was injected at 6 days before estrus to gilts fed high-energy diets. Gilts had restored embryo survival if vitamin A was injected, possibly due to decreased variation in embryo size. Whaley et al. (1997) indicated that vitamin A also increased serum concentrations of progesterone in these studies and slightly advanced the development of the embryo. Whaley et al. (1997) concluded that the improvement in litter size is not due to increasing ovulation rate but to effects on embryo survival. The lack of an effect on ovulation rate in this report supported earlier findings by Britt and Coffey (1993). Da Silveira et al. (1998) reported similar positive effects of vitamin A (450,000 IU retinol palmitate) injection at weaning or mating on the number of piglets born alive, total number born and litter weight. Darroch et al. (1998) reported on a cooperative regional study combining 417 litters from four universities. Intramuscular injections of 250,000 or 500,000 IU of vitamin A were given at weaning and breeding. The researchers reported that the effect of vitamin A injections increased the number of pigs weaned per litter but did not influence the number of pigs born alive. In contrast to the numerous studies reporting positive effects associated with vitamin A injections, Pusateri et al. (1996) found no effect of vitamin A injection (1 million IU) on total or live litter size. Injections were given at weaning or on one of the following days: 0, 2, 6, 10, 13, 19, 30, 70, or 110 post breeding. Pusateri et al. (1996) suggested that possibly multiple injections or a sustained release form of vitamin A or beta-carotene was required to elicit a response. Likewise, Washington et al. (1997) reported no effect on the number of embryos or embryo survival in gilts induced to ovulate. The study involved a very limited number of gilts with an injection of 1 million IU of vitamin A prior to breeding. In disagreement with the numerous positive responses that have been reported with beta-carotene injections, Stender et al. (1998) reported no benefits of beta-carotene injection on litter parameters. Stender et al. (1998) did not report the levels or stage when injection was given. Kolb and Seehawer (1997) reviewed the significance of carotenes and of vitamin A for reproduction of cattle, horses and pigs. Kolb and Seehawer (1997) reported that retinoic acid is necessary for the function of the germ cell epithelial, Sertoli cells and interstitial cells. Promoting the synthesis of proteins, estrogens and progesterone was included in the actions credited to cis and all-trans-retinoic acid.
Except for its role in vision, the function of vitamin A at the cellular level is not yet clear. It is thought that retinyl phosphate may act to regulate cell differentiation. Research findings have indicated that vitamin A increased RNA synthesis by polymerase II in rat testes and that the induced change in transcription was due in part to altered chromatin structure (Porter et al., 1986).
Vitamin A is required for normal disease resistance, which is related to maintenance of mucous membranes and normal functioning of the adrenal gland for production of corticosteroids needed to combat disease. An animal’s ability to resist disease depends on a responsive immune system, with a vitamin A deficiency causing a reduced immune response. In many experiments with laboratory and domestic animals, the effects of both clinical and subclinical deficiencies of vitamin A on the production of antibodies and on the resistance of the different tissues to microbial infection or parasitic infestation have frequently been demonstrated (Kelley and Easter, 1987). Vitamin A-deficient chicks showed rapid loss of lymphocytes, and deficient rats showed atrophy of the thymus and spleen and reduced response to diphtheria and tetanus toxoids (Krishnan et al., 1974). A protective effect of dietary vitamin A supplementation against experimental Staphylococcus aureus mastitis in mice has been reported (Chew et al., 1984). Harman et al. (1963) studied the effect of a vitamin A deficiency on antibody production by baby pigs and found a high correlation coefficient between serum vitamin A and antibody titer. Baby pigs infected with Trichuris suis responded to supplemental vitamin A with an enhanced immunologic response compared with that of controls (Bebravicius et al., 1987). Jyonouchi et al. (1995) suggested that beta-carotene can modulate T-helper cell functions for antibody production in vitro. Recently, Hoskinson et al. (1989) reported the effects of beta-carotene and vitamin A on mitogen-induced lymphocyte proliferation. Both beta-carotene and vitamin A were found to stimulate lymphocyte proliferation in pigs, and beta-carotene was reported to play a specific role in modulating lymphocyte response. Chew et al. (1991) determined that beta-carotene is taken up by circulating lymphocytes but not by neutrophils or erythrocytes. A historical overview of immunity with particular regard to vitamin A has been published by Beisel (1995). Zomborszky-Kovacs et al. (1998) reported that beta-carotene supplementation generated results indicating an increased T-cell immune responsiveness.