Mol. Hum. Reprod. Advance Access published online on October 1, 2008
Molecular Human Reproduction, doi:10.1093/molehr/gan053
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Expression of Epithelial Cadherin in the Human Male Reproductive Tract and Gametes and Evidence of its Participation in Fertilization
2 Instituto de Biología y Medicina Experimental. National Research Council of Argentina (CONICET) - University of Buenos Aires. ZIP Code: 1428ADN. Buenos Aires, Argentina 3Centro Médico Fertilab. ZIP Code: 1116ABI. Buenos Aires, Argentina 4Current address: Research Unit on Biomedical Informatics (GRIB), IMIM, UPF, PRBB, c/Dr, Aiguader 88, E-08003 Barcelona, Spain
5 Correspondence author Mónica H. Vazquez-Levin, Ph.D. Instituto de Biología y Medicina Experimental. CONICET. Vuelta de Obligado 2490. Room B16 & B24. ZIP Code: 1428ADN. Buenos Aires, Argentina. Tel: 54-11-4783-2869, ext 248. Fax: 54-11-4786-2564. E-mail: mhvaz{at}dna.uba.ar
Epithelial cadherin (E-cadherin) has been involved in several calcium dependent cell-cell adhesion events; however, its participation in gamete interaction has not been fully investigated. Our results have demonstrated expression of E-cadherin mRNA in the human male reproductive tract, showing higher levels in the caput, corpus and cauda epididymis than in the testis. The mature 122-KDa E-cadherin was detected in epididymal protein extracts, and was localized in the epithelial cells from the three epididymal regions. Moreover, the 86-KDa E-cadherin ectodomain was found in cauda epididymal and seminal plasma. Western immunoblotting of human sperm protein extracts allowed the identification of four E-cadherin forms (122, 105, 97 and 86 KDa). The protein was localized in the acrosomal region of intact spermatozoa, it remained associated to the head of acrosome-reacted cells, and was also detected on the oocyte surface. A similar localization was determined for other proteins of the adhesion complex (β-catenin and actin). Spermatozoa incubated with anti E-cadherin antibodies showed impaired binding to homologous Zona Pellucida (ZP); in addition, presence of these antibodies inhibited the penetration of human spermatozoa to ZP-free hamster oocytes. The results here presented describe the expression of E-cadherin in the male reproductive tract and gametes, and strongly suggest its involvement in adhesion events during human fertilization. The identification of proteins involved in gamete interaction will contribute to the understanding of the molecular basis of fertilization and help in the diagnosis and treatment of infertility.
Key Words: epididymis/epithelial cadherin/fertilization/seminal plasma/sperm
1 both authors equally contributed to the work
Submitted on May 24, 2008; resubmitted on September 6, 2008; accepted on September 16, 2008.