Vanderbilt University School of Medicine

Orgebin-Crist, Marie-Claire , Ph.D.
Professor of Obstetrics and Gynecology, Emerita; Professor of Cell and Developmental Biology, Emerita

Lab Url: N/A

Phone Number: 615-322-7484

Email Address:M-C.Orgebin-Crist@vanderbilt.edu

Orgebin-Crist, Marie-Claire's picture

Office Address   Mailing Address

Department of OB/GYN R-1215 Medical Ctr. North, Dept. of OB/GYN(2521) 37232-2521


Research Specialty
Epididymal structure and function; development of fertilizing ability in spermatozoa

Research Description
Our work has been directed toward understanding the maturation of spermatozoa in the epididymis and the mechanisms of its regulation. We have shown that, in vivo, spermatozoa develop the capacity to bind to the zona pellucida and to fertilize in a specific segment of the epididymis. At present, we are studying protein secretion by the epididymis and the modification of the sperm surface by epididymal secretory proteins. We have identified and purified several of these proteins: CRISP 1 (cystein-rich secretory protein 1), E-RABP (retinoic acid binding protein), PEBP (phosphatidylethanolamine binding protein), and CRES (cystatin related epididymal protein). We also have identified several glycoprotein-modifying enzymes that either add (glycosyltransferase) or cleave (glycosidase) sugar residues from the sperm surface glycoproteins. We are currently studying the murine E-RABP (Lcn5). This protein belongs to the lipocalin family. Lipocalins are extracellular carrier proteins that bind lipophilic molecules. mE-RABP binds active retinoids (9 cis and all-trans retinoic acid) and is likely involved in the delivery and trafficking of retinoids within the epididymis. To identify the molecular mechanisms underlying the regulation of tissue- and region-specific gene expression in the epididymis, transgenic mice carrying different lengths of the 5' flanking region of the Lcn5 gene driving the CAT reporter gene were produced. We found that important cis-DNA regulatory elements required for the hormonal regulation and spatial expression of the Lcn5 gene reside within 1.8 kb of the 5' flanking region. Using transient transfection assays, we found that the androgen responsiveness of the Lcn5 gene was conferred by an androgen-specific response region located within the first 600-bp of the Lcn5 gene. The Lcn5 gene is localized on mouse chromosome 2. We found that six other related genes, Lcn8, Lcn9, Lcn10, Lcn11, Lcn12, and Lcn13, that evolved by in situ tandem duplication on the same locus form a cluster of epididymis-specific genes. However, each gene has a distinct spatial expression within the epididymis and different regulation. Analysis of the human genome sequence showed the presence of genes on chromosome 9 with genomic organization, chromosomal arrangement, and orientation similar to that of the corresponding murine genes, indicating that the epididymal cluster is evolutionary conserved. A phylogenetic analysis of the new epididymal proteins reveals their spread position in the lipocalin protein family tree. This suggests preservation of regulatory sequences, while protein sequences have greatly diverged, reflecting functional diversity and possibly multifunctionality. The candidate ancestor gene likely appeared in amniotes and the duplications generating the cluster occurred at least in the common ancestor of rodents and primates. The presence and conservation from lizard to man of a cluster of genes encoding epididymal lipocalins, differently regulated and regionalized in the epididymis, strongly suggests that these proteins may play an important role in epididymal function.

Publications
Kichiya Suzuki, Xiuping Yu, Pierre Chaurand, Yoshihiko Araki, Jean-Jacques Lareyre, Richard M. Caprioli, Marie-Claire Orgebin-Crist, Robert J. Matusik. Epididymis-specific lipocalin promoters. Asian J Androl, 9(July), 515-521, 2007.

Suzuki, K, Yu, X, Chaurand, P, Araki, Y, Lareyre, JJ, Caprioli, RM, Matusik, RJ, Orgebin-Crist, MC. Epididymis-specific promoter-driven gene targeting: A transcription factor which regulates epididymis-specific gene expression. Mol Cell Endocrinol. 250, 184-189, , , 2006.

Yu, X, Gupta, A, Wang, Y, Suzuki, K, Mirosevich, J, Orgebin-Crist, MC, Matusik, RJ. Foxa1 and foxa2 interact with the androgen receptor to regulate prostate and epididymal genes differentially. Ann N Y Acad Sci, 1061, 77-93, 2005.

Kirchhoff C, Araki Y, Huhtaniemi I, Matusik RJ, Osterhoff C, Poutanen M, Samalecos A, Sipila P, Suzuki K, Orgebin-Crist M-C. . Immortalization by large T-antigen of the adult epididymal duct epithelium. Mol Cell Endocrinol 216, . Mol Cell Endocrinol, (216), 83-94, 2004.

Suzuki K, Lareyre JJ, Sanchez D, Gutierrez G, Araki Y, Matusik RJ, Orgebin-Crist MC. . Molecular evolution of epididymal lipocalin genes localized on mouse chromosome 2. . Gene, 339, 49-59, 2004.

Suzuki, K, Drevet, J, Hinton, BT, Huhtaniemi, I, Lareyre, J-J, Matusik, RJ, Pons, E, Poutanen, M, Sipila, P, Orgebin-Crist, M-C. Epididymis-specific promoter-driven gene targeting: a new approach to control epididymal function?. Mol Cell Endocrinol, 216(), 15-22, 2004.

Suzuki, K, Drevet, J, Hinton, BT, Huhtaniemi, I, Lareyre, JJ, Matusik, RJ, Pons, E, Poutanen, M, Sipil??, P, Orgebin-Crist, MC. Epididymis-specific promoter-driven gene targeting: a new approach to control epididymal function. Mol Cell Endocrinol, 216(1-2), 15-22, 2004.

Suzuki, K, Lareyre, JJ, S?!nchez, D, Gutierrez, G, Araki, Y, Matusik, RJ, Orgebin-Crist, MC. Molecular evolution of epididymal lipocalin genes localized on mouse chromosome 2. Gene, 339, 49-59, 2004.

Cooper TG, Wagenfeld A, Cornwall GA, Hsia N, Chu ST, Orgebin-Crist M-C, Drevet J, Vernet P, Avram C, Nieschlag E, Yeung C-H. Gene and protein expression in the epididymis of infertile c-ros receptor tyrosine kinase-deficient mice. Biol Reprod 69, 1750-1762, 2003.

Orgebin-Crist, M-C. The Epididymis in the post-genome era. In: The Third International Conference on the Epididymis, BT Hinton and TT Turner, Eds., The Van Doren Co., 2-22, 2003.

Ralph JL, Orgebin-Crist M-C, Lareyre J-J, Nelson CC. Disruption of androgen regulation in the prostate by the environmental contaminant hexachlorobenzene. Environmental Health Perspectives 111(4), 461-466, 2003.

Chaurand, Pierre, Fouchecourt, Sophie, DaGue, Beverly B, Xu, Baogang J, Reyzer, Michelle L, Orgebin-Crist, Marie-Claire, Caprioli, Richard M. Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry. Proteomics, 3(11), 2221-2239, 2003.

Fouchecourt, Sophie, Lareyre, Jean-Jacques, Chaurand, Pierre, DaGue, Beverly B, Suzuki, Kichiya, Ong, David E, Olson, Gary E, Matusik, Robert J, Caprioli, Richard M, Orgebin-Crist, Marie-Claire. Identification, immunolocalization, regulation, and postnatal development of the lipocalin EP17 (epididymal protein of 17 kilodaltons) in the mouse and rat epididymis. Endocrinology, 144(3), 887-900, 2003.

Suzuki, Kichiya, Araki, Yoshihiko, Zhu, Mei-Ying, Lareyre, Jean-Jacques, Matusik, Robert J, Orgebin-Crist, Marie-Claire. The 5'-flanking region of the murine epididymal protein of 17 kilodaltons gene targets transgene expression in the epididymis. Endocrinology, 144(3), 877-86, 2003.

Cooper TG, Yeung C-H, Jones R, Orgebin-Crist M-C, Robaire B. Rebuttal of a role for the epididymis in sperm quality control by phagocytosis of defective sperm. J Cell Science 115, 5-7, 2002.

Cornwall GA, Lareyre J-J, Matusik RJ, Hinton BT, Orgebin-Crist M-C. Gene expression and epididymal function. In: The Epididymis: From Molecules to Clinical Practice, B Robaire and BT Hinton, Eds., Kluwer Academic/Plenum Publishers, New York, 169-199, 2002.

Orgebin-Crist M-C, Lareyre J-J, Suzuki K, Araki Y, Fouchecourt S, Matusik RJ, Ong DE. Retinoids and epididymal function. In: The Epididymis: From Molecules to Clinical Practice, B Robaire and BT Hinton, Eds., Kluwer Academic/Plenum Publishrs, New York, 339-352, 2002.

Araki, Yoshihiko, Suzuki, Kichiya, Matusik, Robert J, Obinata, Masuo, Orgebin-Crist, Marie-Claire. Immortalized epididymal cell lines from transgenic mice overexpressing temperature-sensitive simian virus 40 large T-antigen gene. J Androl, 23(6), 854-69, 2002.

Fouchecourt, Sophie, Chaurand, Pierre, DaGue, Beverly B, Lareyre, Jean-Jacques, Matusik, Robert J, Caprioli, Richard M, Orgebin-Crist, Marie-Claire. Epididymal lipocalin-type prostaglandin D2 synthase: identification using mass spectrometry, messenger RNA localization, and immunodetection in mouse, rat, hamster, and monkey. Biol Reprod, 66(2), 524-33, 2002.

Kurita A, Takizawa T, Takayama T, Totsukawa K, Matsubara S, Shibahara H., Orgebin-Crist M-C, Sendo F, Shinkai Y, Araki Y. Identification, cloning, and initial characterization of a novel mouse testicular germ cell-specific antigen. Biol Reprod 64, 935-945, 2001.

Lareyre, J J, Winfrey, V P, Kasper, S, Ong, D E, Matusik, R J, Olson, G E, Orgebin-Crist, M C. Gene duplication gives rise to a new 17-kilodalton lipocalin that shows epididymal region-specific expression and testicular factor(s) regulation. Endocrinology, 142(3), 1296-308, 2001.

Allard S, Adin P, Gouedard L, di Clemente N, Josso N, Orgebin-Crist M-C, Picard J-Y, Xavier F. Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement of beta-catenin. Development, 127, 3349-3360, 2000.

Chayko, C A, Orgebin-Crist, M C. Targeted disruption of the cation-dependent or cation-independent mannose 6-phosphate receptor does not decrease the content of acid glycosidases in the acrosome. J Androl, 21(6), 944-53, 2000.

Chayko, C A, Orgebin-Crist, M C, Skudlarek, M D, Tulsiani, D R. Biosynthesis, processing, and subcellular localization of rat sperm beta-D-galactosidase. Biol Reprod, 63(3), 688-96, 2000.

Lareyre, J J, Reid, K, Nelson, C, Kasper, S, Rennie, P S, Orgebin-Crist, M C, Matusik, R J. Characterization of an androgen-specific response region within the 5' flanking region of the murine epididymal retinoic acid binding protein gene. Biol Reprod, 63(6), 1881-92, 2000.

Ong, D E, Newcomer, M E, Lareyre, J J, Orgebin-Crist, M C. Epididymal retinoic acid-binding protein. Biochim Biophys Acta, 1482(1-2), 209-17, 2000.

Lareyre, J J, Thomas, T Z, Zheng, W L, Kasper, S, Ong, D E, Orgebin-Crist, M C, Matusik, R J. A 5-kilobase pair promoter fragment of the murine epididymal retinoic acid-binding protein gene drives the tissue-specific, cell-specific, and androgen-regulated expression of a foreign gene in the epididymis of transgenic mice. J Biol Chem, 274(12), 8282-90, 1999.

Abou-Haila A, Orgebin-Crist M-C, Skudlarek MD, Tulsiani DRP. Identification and androgen regulation of egasyn in the mouse epididymis. Biochim Biophys Acta 1401, 177-186, 1998.

Akatsuka K, Yoshida-Komiya H, Tulsiani DRP, Orgebin-Crist M-C, Hiroi M, Araki Y. Rat zona pellucida glycoproteins: Molecular cloning and characterization of the three major components. Molec Reprod Dev 51, 454-467, 1998.

Lareyre, J J, Mattei, M G, Kasper, S, Newcomer, M E, Ong, D E, Matusik, R J, Orgebin-Crist, M C. Structure and putative function of a murine epididymal retinoic acid-binding protein (mE-RABP). J Reprod Fertil Suppl, 53(), 59-65, 1998.

Lareyre, J J, Mattei, M G, Kasper, S, Ong, D E, Matusik, R J, Orgebin-Crist, M C. Genomic organization and chromosomal localization of the murine epididymal retinoic acid-binding protein (mE-RABP) gene. Mol Reprod Dev, 50(4), 387-95, 1998.

Lareyre, J J, Zheng, W L, Zhao, G Q, Kasper, S, Newcomer, M E, Matusik, R J, Ong, D E, Orgebin-Crist, M C. Molecular cloning and hormonal regulation of a murine epididymal retinoic acid-binding protein messenger ribonucleic acid. Endocrinology, 139(6), 2971-81, 1998.

Orgebin-Crist, M C. The epididymis across 24 centuries. J Reprod Fertil Suppl, 53, 285-92, 1998.

Tulsiani, D R, Orgebin-Crist, M C, Skudlarek, M D. Role of luminal fluid glycosyltransferases and glycosidases in the modification of rat sperm plasma membrane glycoproteins during epididymal maturation. J Reprod Fertil Suppl, 53, 85-97, 1998.

Abou-Haila, A., Tulsiani, D.R.P., Skudlarek, M.D., and Orgebin-Crist, M.-C. Androgen regulation of molecular forms of beta-D-glucuronidase in the mouse epididymis. Comparison with liver and kidney. J Androl, 17, 194-207, 1996.

Tulsiani, D R, Chayko, C A, Orgebin-Crist, M C, Araki, Y. Temporal surge of glycosyltransferase activities in the genital tract of the hamster during the estrous cycle. Biol Reprod, 54(5), 1032-7, 1996.

Tulsiani, D R, NagDas, S K, Skudlarek, M D, Orgebin-Crist, M C. Rat sperm plasma membrane mannosidase: localization and evidence for proteolytic processing during epididymal maturation. Dev Biol, 167(2), 584-95, 1995.

Tulsiani, D R, Skudlarek, M D, Araki, Y, Orgebin-Crist, M C. Purification and characterization of two forms of beta-D-galactosidase from rat epididymal luminal fluid: evidence for their role in the modification of sperm plasma membrane glycoprotein(s). Biochem J, 305 ( Pt 1), 41-50, 1995. PMCID:1136427

Vierula, M.E., Rankin, T.L., and Orgebin-Crist, M.-C. Electron microscopic immunolocalization of the 18 and 29 kilodaltons secretary proteins in the mouse epididymis; evidence for differential uptake by clear cells. Microscopy Research and Technique, 30, 24-36, 1995.

Nagdas, S K, Araki, Y, Chayko, C A, Orgebin-Crist, M C, Tulsiani, D R. O-linked trisaccharide and N-linked poly-N-acetyllactosaminyl glycans are present on mouse ZP2 and ZP3. Biol Reprod, 51(2), 262-72, 1994.

Schmitt, M C, Jamison, R S, Orgebin-Crist, M C, Ong, D E. A novel, testis-specific member of the cellular lipophilic transport protein superfamily, deduced from a complimentary deoxyribonucleic acid clone. Biol Reprod, 51(2), 239-45, 1994.

Skudlarek, M D, Tulsiani, D R, Nagdas, S K, Orgebin-Crist, M C. Beta-D-galactosidase of rat spermatozoa: subcellular distribution, substrate specificity, and molecular changes during epididymal maturation. Biol Reprod, 49(2), 204-13, 1993.

Tulsiani, D R, Skudlarek, M D, Holland, M K, Orgebin-Crist, M C. Glycosylation of rat sperm plasma membrane during epididymal maturation. Biol Reprod, 48(2), 417-28, 1993.

Tulsiani, D R, Skudlarek, M D, Nagdas, S K, Orgebin-Crist, M C. Purification and characterization of rat epididymal-fluid alpha-D-mannosidase: similarities to sperm plasma-membrane alpha-D-mannosidase. Biochem J, 290 ( Pt 2), 427-36, 1993. PMCID:1132291

Holland, M K, Vreeburg J T, Orgebin-Crist, M C. Testicular regulation of epididymal protein secretion. J Androl, 13, 266-273, 1992

Vreeburg, J T M, Holland, M K, Orgebin-Crist, M C. Binding of epididymal proteins to rat spermatozoa in vivo. Biol Reprod, 47, 588-597, 1992.

Araki, Y, Orgebin-Crist, M C, Tulsiani, D R. Qualitative characterization of oligosaccharide chains present on the rat zona pellucida glycoconjugates. Biol Reprod, 46(5), 912-9, 1992.

Araki, Y, Vierula, M E, Rankin, T L, Tulsiani, D R, Orgebin-Crist, M C. Isolation and characterization of a 25-kilodalton protein from mouse testis: sequence homology with a phospholipid-binding protein. Biol Reprod, 47(5), 832-43, 1992.

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. Expression of an endogenous murine leukemia virus-related proviral sequence is androgen regulated and primarily restricted to the epididymis/vas deferens and oviduct/uterus. Biol Reprod, 47(4), 665-75, 1992.

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. Differential expression of the mouse mitochondrial genes and the mitochondrial RNA-processing endoribonuclease RNA by androgens. Mol Endocrinol, 6(7), 1032-42, 1992.

Cornwall, G A, Orgebin-Crist, M C, Hann, S R. The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis. Mol Endocrinol, 6(10), 1653-64, 1992.

Nagdas, S K, Skudlarek, M D, Orgebin-Crist, M C, Tulsiani, D R. Biochemical alterations in the proacrosin-acrosin system during epididymal maturation of the rat spermatozoa. J Androl, 13(1), 36-43, 1992.

Rankin, T L, Ong, D E, Orgebin-Crist, M C. The 18-kDa mouse epididymal protein (MEP 10) binds retinoic acid. Biol Reprod, 46(5), 767-71, 1992.

Rankin, T L, Tsuruta, K J, Holland, M K, Griswold, M D, Orgebin-Crist, M C. Isolation, immunolocalization, and sperm-association of three proteins of 18, 25, and 29 kilodaltons secreted by the mouse epididymis. Biol Reprod, 46(5), 747-66, 1992.

Skudlarek, M D, Tulsiani, D R, Orgebin-Crist, M C. Rat epididymal luminal fluid acid beta-D-galactosidase optimally hydrolyses glycoprotein substrate at neutral pH. Biochem J, 286 ( Pt 3), 907-14, 1992. PMCID:1132989

Tulsiani, D R, Nagdas, S K, Cornwall, G A, Orgebin-Crist, M C. Evidence for the presence of high-mannose/hybrid oligosaccharide chain(s) on the mouse ZP2 and ZP3. Biol Reprod, 46(1), 93-100, 1992.

Vierula, M E, Araki, Y, Rankin, T L, Tulsiani, D R, Orgebin-Crist, M C. Immunolocalization of a 25-kilodalton protein in mouse testis and epididymis. Biol Reprod, 47(5), 844-56, 1992.

Cornwall, G A, Tulsiani, D R, Orgebin-Crist, M C. Inhibition of the mouse sperm surface alpha-D-mannosidase inhibits sperm-egg binding in vitro. Biol Reprod, 44(5), 913-21, 1991.

Skudlarek, M D, Orgebin-Crist, M C, Tulsiani, D R. Asparagine-linked glycoprotein biosynthesis in rat epididymis. Presence of a mannosidase II-like enzyme. Biochem J, 277 ( Pt 1), 213-21, 1991. PMCID:1151212

Cornwall, G A, Vreeburg, J T, Holland, M K, Orgebin-Crist, M C. Interactions of labeled epididymal secretory proteins with spermatozoa after injection of 35S-methionine in the mouse. Biol Reprod, 43(1), 121-9, 1990.

Tulsiani, D R, Skudlarek, M D, Orgebin-Crist, M C. Swainsonine induces the production of hybrid glycoproteins and accumulation of oligosaccharides in male reproductive tissues of the rat. Biol Reprod, 43(1), 130-8, 1990.

Tulsiani, D R, Skudlarek, M D, Orgebin-Crist, M C. Human sperm plasma membranes possess alpha-D-mannosidase activity but no galactosyltransferase activity. Biol Reprod, 42(5-6), 843-58, 1990.

Rankin, T L, Holland, M K, Orgebin-Crist, M C. Lectin binding characteristics of mouse epididymal fluid and sperm extracts. Gamete Res, 24(4), 439-51, 1989.

Tulsiani, D R, Skudlarek, M D, Orgebin-Crist, M C. Novel alpha-D-mannosidase of rat sperm plasma membranes: characterization and potential role in sperm-egg interactions. J Cell Biol, 109(3), 1257-67, 1989. PMCID:2115747

Holland, M K, Orgebin-Crist, M C. Characterization and hormonal regulation of protein synthesis by the murine epididymis. Biol Reprod, 38(2), 487-96, 1988.

Holland, M K, Orgebin-Crist, M C. Epididymal protein synthesis and secretion in strains of mice bearing single gene mutations which affect fertility. Biol Reprod, 38(2), 497-510, 1988.

Skudlarek, M D, Orgebin-Crist, M C. Effect of swainsonine on rat epididymal glycosidases. J Reprod Fertil, 84(2), 611-7, 1988.

Holland, M K, Rogers, B J, Orgebin-Crist, M C, Danzo, B J. Effects of photoperiod on androgen-binding protein and sperm fertilizing ability in the hamster. J Reprod Fertil, 81(1), 99-112, 1987.

Orgebin-Crist, M C, Hoffman, L H, Olson, G E, Skudlarek, M D. Secretion of proteins and glycoproteins by perifused rabbit corpus epididymal tubules: effect of castration. Am J Anat, 180(1), 49-68, 1987.


Postdoctoral Position Available
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Postdoctoral Position Details
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Updated Date
10/01/2007



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