Retinoic acid metabolism and signaling pathways in the adult and developing mouse testis

Endocrinology. 2006 Jan;147(1):96-110. doi: 10.1210/en.2005-0953. Epub 2005 Oct 6.


As a first step in investigating the role of retinoic acid (RA) in mouse testis, we analyzed the distribution pattern of the enzymes involved in vitamin A storage (lecithin:retinol acyltransferase), RA synthesis (beta-carotene 15,15'-monoxygenase and retinaldehyde dehydrogenases) and RA degradation (cytochrome P450 hydroxylases) as well as those of all isotypes of receptors transducing the RA signal [RA receptors (RARs) and rexinoid receptors (RXRs)]. Our data indicate that in adult testis 1) cytochrome P450 hydroxylase enzymes may generate in peritubular myoid cells a catabolic barrier that prevents circulating RA and RA synthesized by Leydig cells to enter the seminiferous epithelium; 2) the compartmentalization of RA synthesis within this epithelium may modulate, through paracrine mechanisms, the coupling between spermatogonia proliferation and spermatogenesis; 3) retinyl esters synthesized in round spermatids by lecithin:retinol acyltransferase may be transferred and stored in Sertoli cells, in the form of adipose differentiation-related protein-coated lipid droplets. We also show that RARalpha and RXRbeta are confined to Sertoli cells, whereas RARgamma is expressed in spermatogonia and RARbeta, RXRalpha, and RXRgamma are colocalized in step 7-8 spermatids. Correlating these expression patterns with the pathological phenotypes generated in response to RAR and RXR mutations and to postnatal vitamin A deficiency suggests that spermiation requires RXRbeta/RARalpha heterodimers in Sertoli cells, whereas spermatogonia proliferation involves, independently of RXR, two distinct RAR-mediated signaling pathways in both Sertoli cells and spermatogonia. Our data also suggest that the involvement of RA in testis development starts when primary spermatogonia first appear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology
  • Retinoic Acid Receptor alpha
  • Signal Transduction
  • Testis / growth & development*
  • Testis / physiology
  • Tretinoin / metabolism*


  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • retinoic acid receptor beta
  • Tretinoin