Vitamin A and reproduction in rats

Abstract

Retinoic acid (vitamin A acid), the carboxylic acid corresponding to the primary alcohol retinol (vitamin A), has previously been thought to fulfil all the functions of vitamin A except in vision, since rats fed a diet deficient in retinol but supplemented with retinoic acid grow well, outwardly appearing healthy, yet become blind. This paper reports that female rats on such a diet had normal oestrous cycles and became pregnant when mated, but always resorbed the foetuses and no litters were born. The first abnormalities detected were necrosis and slight polymorph infiltration around the periphery of the placental disk about the sixteenth day of pregnancy. Supplementation with retinol as late as the tenth day resulted in the birth of a healthy litter. Retinoic acid therefore maintained the early but not the later stages of gestation. When very small amounts of retinol were given during pregnancy, dead or weak young were born; on higher supplements of the vitamin, litters were weaned successfully. By this means young rats were produced with negligible stores of retinol. Male rats fed retinoic acid but not retinol had small and often oedematous testes. The germinal epithelium sloughed off and in some tubules the lumen was obliterated, but in others the lumen remained, and in these some spermatocytes and spermatogonia were held tenaciously. The seminal vesicles were smaller than in controls given retinol. In rats born with negligible stores of retinol—see above—and maintained on retinoic acid, the testes remained infantile; spermatids were never formed. Feeding retinol restored spermatogenesis in degenerate testes and promoted the normal development of testes that had remained infantile; it also ensured the growth of the seminal vesicles. Retinoic acid did not therefore serve in reproduction, although it replaced the true vitamin in maintaining life, growth and general health. Besides the latter so-called systemic function, vitamin A must have a discrete and specific role in reproduction, viz. that performed by retinol but not by retinoic acid. From among the many previously reported features of disordered reproduction in vitamin A-deficient animals, it was possible to distinguish which had arisen from a failure of this specifically ‘reproductive’ role and which from a ‘systemic’ deficiency. The inactivity of retinoic acid in reproduction demonstrates that in rats vitamin A has not two, as previously thought, but three dissociable modes of action: (1) systemic; (2) in vision; and (3) in reproduction.

Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein

“…For instance, it has been proposed that RBP of Sertoli cell origin may facilitate the transport of ROL through the blood-tissue barrier (Shingleton et al, 1989), but whether RBP is actually expressed in the testis is uncertain (Soprano and Blaner, 1994). On the other hand, experiments conducted over the past decades in the rat have demonstrated that RA is instrumental to testicular physiology: VAD induces a rapid testicular degeneration characterized by a complete disappearance of all meiotic and postmeiotic germ cells (Howell et al, 1963;Thompson et al, 1964;van Pelt and de Rooij, 1990a;and references therein) and systemic administration of RA to vitamin A-deficient rats restores spermatogenesis from growth-arrested A spermatogonia (van Pelt and de Rooij, 1991).…”

Evidence for the Expression of Alcohol Dehydrogenase Class I Gene in Rat Uterus and Its Up-regulation by Progesterone

“…Retinol deficiency is associated with abnormal growth and development, keratinization of cutis and mucosa, lowered resistance to infection [26]. Also infertility is known to occur in cases of retinol deficiency in male and female [26]. It was reported that cellular-retinol binding protein and cellular-RA binding protein exist in the epithelial cells and stromal cells of the uterus, and that their expressions are regulated during menstrual cycle, estrus cycle and estrogen [27][28][29][30].…”

“…Retinol is required for normal growth and development in vertebrates animals. Retinol deficiency is associated with abnormal growth and development, keratinization of cutis and mucosa, lowered resistance to infection [26]. Also infertility is known to occur in cases of retinol deficiency in male and female [26].…”

Metabolic studies on retinoic acid in the rat

“…However, it was found to be inactive in vision (Dowling & Wald, 1960) and reproduction (Thompson, Howell & Pitt, 1964). The conversion of retinal into retinol by retinal reductase (Futterman & Saslaw, 1961;Wald & Hubbard, 1949;Bliss, 1951) and the transformation of retinal into retinoic acid by retinal oxidase (Dmitrovskii, 1961;Futterman, 1962;Elder & Topper, 1962;Bamji, Mahadevan, Lakshmanan & Murthy, 1962) have both been demonstrated in liver and other tissues.…”