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This Article Full Text Full Text (PDF) All Versions of this Article: 71/5/1453    most recent biolreprod.104.031740v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Avellar, M. C. W. Articles by Hall, S. H. Search for Related Content PubMed PubMed Citation Articles by Avellar, M. C. W. Articles by Hall, S. H. Agricola Articles by Avellar, M. C. W. Articles by Hall, S. H.

Differential Expression and Antibacterial Activity of Epididymis Protein 2 Isoforms in the Male Reproductive Tract of Human and Rhesus Monkey (Macaca mulatta)¹

Section of Experimental Endocrinology,³ Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, SP 04044-020, Brazil Department of Pediatrics⁴ Department of Cell and Developmental Biology,⁵ University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7500

The epididymis protein 2 (EP2) gene, the fusion of two ancestral ß-defensin genes, is highly expressed in the epididymis and subject to species-specific regulation at the levels of promoter selection, transcription, and mRNA splicing. EP2 mRNA expression is also androgen dependent, and at least two of the secreted proteins bind spermatozoa. Alternative splicing produces more than 17 different EP2 mRNA variants. In this article, the expression of EP2 variants was profiled in different tissues from the human and rhesus monkey (Macaca mulatta) male reproductive tract using reverse transcriptase-polymerase chain reaction. Different EP2 mRNA variants were identified not only in human and rhesus testis and epididymis but also in the novel sites, seminal vesicle and prostate. Immunolocalization of EP2 protein in epithelial cells from rhesus and human seminal vesicle demonstrated that EP2 transcripts are translated in these tissues. In addition, two novel splicing variants, named EP2R and EP2S, were discovered. EP2C was the only splice variant expressed in all tissues tested from rhesus monkey. However, expression was not detected in human testis or seminal vesicle. For the first time, bactericidal function was demonstrated for EP2C, EP2K, and EP2L. Taken together, the results indicate that EP2 expression is more widespread in the male reproductive tract than realized previously. Whereas the activity of every EP2 variant tested thus far is antibacterial, further investigation may reveal additional physiological roles for EP2 peptides in the primate male reproductive tract.

¹ Supported partially by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 99/1777-1), Brazil, and by the T.W. Fogarty International Center for Training and Research in Population and Health, USA D43TW/HD00627 (subcontract UNIFESP/UNC 5-53284). Support was provided by the CICCR Program of the Contraceptive Research and Development Program, Eastern Virginia Medical School. The views expressed by the authors do not necessarily reflect the views of CONRAD or CICCR. This work was also supported by grants from the Andrew W. Mellon Foundation and the National Institutes of Health (R37-HD04466, through cooperative agreement U54-HD35041).

² Correspondence: Maria Christina W. Avellar, Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo—Escola Paulista de Medicina, Rua 03 de maio 100, INFAR, Vila Clementino, São Paulo, SP 04044-020, Brazil. FAX: 55 11 5576 4448; avellar{at}farm.epm.br

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