Retinoid-Sensitive Steps in Steroidogenesis in Fetal and Neonatal Rat Testes: In Vitro and In Vivo Studies

• Published in: Biology of reproduction 2004-06, Vol.70 (6), p.1814-1821
• Main Authors: Livera, G, Pairault, C, Lambrot, R, Lelievre-Pegorier, M, Saez, J. M, Habert, R, Rouiller-Fabre, V
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Base Sequence; Biological and medical sciences; Cell Differentiation - drug effects; Contents; DNA - genetics; Early stages. Segmentation. Gastrulation. Neurulation; embryo; Embryology: invertebrates and vertebrates. Teratology; Female; Fetus - drug effects; Fetus - metabolism; Fundamental and applied biological sciences. Psychology; Gestational Age; Leydig cells; Leydig Cells - cytology; Leydig Cells - drug effects; Leydig Cells - metabolism; Luteinizing Hormone - pharmacology; Male; male sexual function; Organ Culture Techniques; Pregnancy; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; RNA, Messenger - metabolism; Steroid 17-alpha-Hydroxylase - genetics; testis; Testis - cytology; Testis - drug effects; Testis - metabolism; testosterone; Testosterone - biosynthesis; Tretinoin - pharmacology; Vertebrates: reproduction; Vitamin A Deficiency - metabolism
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.103.021451

Retinoic acid (RA) was recently shown to modify testosterone secretion of the fetal testis in vitro. We characterized this effect by culturing rat testes explanted at various ages, from Fetal Day 14.5 to Postnatal Day 3. In basal medium, RA inhibited, in a dose-dependent manner, both basal and acute LH-stimulated testosterone secretion by testes explanted on Fetal Days 14.5, 15.5, and 16.5. It had no effect on testes from older animals. The negative effect of RA did not result from a diminution in the number of Leydig cells but from a decrease in P450c17 mRNA levels and in LH-stimulated cAMP production. However, the RA-induced decrease in P450C17 mRNA levels was also observed with neonatal testes, suggesting that this enzymatic step is no longer rate limiting at this developmental stage. To study the physiological relevance of RA effects, we used fetuses and neonates issued from mothers fed a vitamin A-deficient (VAD) diet, resulting in a threefold decrease of plasma retinol concentration. On Fetal Day 18.5 and on Posnatal Day 3, testosterone secretion by the testis ex vivo was significantly increased in VAD animals. This shows that the endogenous retinol inhibits differentiation and/or function of fetal Leydig cells before Fetal Day 18.5 and is required for the normal regression of fetal Leydig cell function that occurs after Fetal Day 18.5. In conclusion, our results show that retinoids play a negative role on the steroidogenic activity during the differentiation of rat fetal Leydig cells.