Role of Vitamin A in Male Germ-Cell Development

Abstract

It has been known since the 1920s that vitamin A is required for normal spermatogenesis (1, 2). Depletion of vitamin A from the diet was shown to cause spermatogenic arrest and testicular atrophy, whereas the replenishment of retinol, the principal form of vitamin A, to the vitamin A-deficient (VAD) animals restored spermatogenesis (3). Since then, numerous investigators have analyzed the cell types that are present in the VAD testis (4–8) and described various spermatogenic depletion and retinol replenishment processes resulting in synchronization of spermatogenic stages in the replenished testes (9–15). However, to date, the molecular mechanism by which vitamin A is obligatory for spermatogenesis has not been elucidated. In fact, which cell types in the testis respond directly to the vitamin A signal is not completely clear. The challenge is to define which individual cells in the testis are the direct target of vitamin A and to understand how these cells interact with other cells to determine whether they proliferate, differentiate, survive, or degenerate. Recently, it has been established that nuclear retinoid receptors, members of the steroid/thyroid superfamily of receptors, which are now accepted as the transcription factors that mediate the retinoic acid signal in most tissues (16), are also important mediators of the vitamin A signals in testis (17–22).