Retinoic Acid Is Able to Reinitiate Spermatogenesis in Vitamin A-Deficient Rats and High Replicate Doses Support the Full Development of Spermatogenic Cells

Abstract

The effect of various doses of retinoic acid (RA) on the seminiferous epithelium in vitamin A-deficient rats has been studied. Although it was generally thought that RA was not able to reinitiate spermatogenesis in vitamin A-deficient rats, one injection of 5 mg RA strongly stimulated the proliferative activity of A-spermatogonia within 24 h, as evidenced by a 7-fold increase in the number of bromodeoxyuridine-labeled A-spermatogonia. Ten days after RA administration, B-spermatogonia or preleptotene spermatocytes were seen in most of the seminiferous tubules. After 15 days, zygotene spermatocytes were present. Hence, RA is able to induce a massive and synchronized development of A-spermatogonia into spermatocytes. When RA was given once, combined with a RA-containing diet, only few of the zygotene spermatocytes present on day 15 were able to develop into pachytene spermatocytes, which did not develop into spermatids. In subsequent epithelial cycles new B-spermatogonia and spermatocytes were formed, although in lower numbers than during the first cycle after RA injection. When RA was given once a week, the formation of B-spermatogonia and preleptotene spermatocytes continued at a higher level. Also, more pachytene spermatocytes were formed, some of which were able to develop into spermatids. Finally, when RA was injected twice a week, even more pachytene spermatocytes and round spermatids were found after 36 days, and after 49 days elongated spermatids were found in all animals. It is concluded that RA, similar to retinol, is able to induce synchronous proliferation and differentiation of A-spermatogonia. When repeated injections are given, RA is able to support the full development of spermatogenic cells into elongated spermatids.

Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand

“…the transition from type B spermatogonia to primary spermatocytes, even though it has been reported that mouse germ cells cocultured with the 15-P1 cell line, expressing the transmembrane form of KL, can undergo transmeiotic progression in culture, whereas the soluble form of KL was reported to antagonize this effect (Vincent et al, 1998). Up to now, the only agent which has been postulated to have a (direct or indirect) role in the induction of meiotic entry is all-trans retinoic acid (ATRA) (van Pelt and de Rooij, 1991;Bowles et al, 2006;Koubova et al, 2006). Interestingly, Wang and Culty (2007) have recently found that ATRA stimulates kit expression in prepuberal spermatogonia.…”

Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges

“…At first, studies demonstrated that normal spermatogenesis could only resume if vitamin A (retinol) was given to the deficient mice and that the same results were not observed upon Gonocyte and spermatogonia differentiation R141 RA administration (Ahluwalia & Bieri 1971, Huang et al 1983. However, later studies demonstrated that RA could also stimulate normal spermatogenesis in these deficient mice, but at a much higher dose than retinol, probably due to differences in the levels of binding proteins for each of these retinoids in Sertoli cells (Van Pelt & de Rooij 1991).…”

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

“…It is widely accepted that RA represents the vitamin A metabolite that is active in mouse spermatogenesis (van Pelt and de Rooij, 1991;Gaemers et al, 1998). RA acts through binding to RARs (Chambon, 1996(Chambon, , 2005.…”

“…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).…”