PARENT SESSION
MINISYMPOSIUM XI: Sperm Surface Modifications in the Epididymis
Wednesday, August 1, 2001, 10:30 AM-12:00 PM
Westin-Confederation I
Chair: Edda Toepfer-Peterson
Speakers: Edda Toepfer-Peterson, Louis Hermo, Jean-Jacques Lareyre

REGION-SPECIFIC EXPRESSION, HORMONAL REGULATION, EVOLUTIONARY CONSERVATION AND PUTATIVE FUNCTION(S) OF GENES ENCODING EPIDIDYMIS-SPECIFIC LIPOCALINS.

Lareyre, Jean-Jacques¹, Suzuki, Kichiya², Fouchecourt, Sophie², Araki, Yoshihiko², Matusik, Robert³, Orgebin-Crist, Marie-Claire², ^{1 2 3}

ABSTRACT- During their transit through the epididymis, mammalian spermatozoa undergo a complex process of maturation resulting in their forward motility and fertilizing ability. In the epididymis, spermatozoa are exposed to microenvironments created by the absorptive and secretory activities of the epithelial cells, and it is believed that interaction between epididymal secretory proteins and the sperm plasma membrane is involved in the sperm maturation process. We have identified a murine epididymal secretory protein binding retinoic acid and termed mE-RABP. Analysis of the 5' flanking region of the mE-RABP gene revealed a novel gene, termed mEP17, homologous to the mE-RABP gene and localized 1.7 kb upstream from the mE-RABP gene. Exon/intron boundaries of the mEP17 and mE-RABP genes are identical suggesting that these genes were generated by duplication within the proximal region of mouse chromosome 2. Interestingly, mE-RABP and mEP17 genes display a highly regionalized and complementary expression pattern within the caput epididymidis. In addition, these genes are differently regulated. mE-RABP is androgen-regulated whereas mEP17, but not mE-RABP, is dependent on testicular factors present into the luminal fluid. To identify the molecular mechanisms underlying the regulation of tissue- and region-specific gene expression in the epididymis, transgenic mice carrying different length of the 5' flanking region of these genes driving the CAT reporter gene were produced. We demonstrate that important cis-DNA regulatory elements required for the hormonal regulation and spatial expression of the mE-RABP gene reside within 5-kb of the 5' flanking region. Using transient transfection assays, we found that the androgen responsiveness of the mE-RABP gene was conferred by an androgen-specific response region located within the first 600-bp of the mE-RABP gene. The proteins encoded by the mE-RABP and mEP17 genes belong to the lipocalin superfamily. Lipocalins are extracellular carrier proteins that bind lipophilic molecules. It is therefore not surprising that mE-RABP bind to active retinoids (9 cis and all-trans retinoic acid). Although the mEP17 ligand has yet to be identified, it is likely that mE-RABP and mEP17 are involved in the trafficking of retinoids within the epididymis. Finally, we bring evidence that these lipocalins are conserved during evolution from lizard to man suggesting that they may play an important role in the epididymal function. Putative functions of these epididymal lipocalins will be discussed.

KEY WORDS: androgen, epididymis, lipocalin, retinoic acid