Differential expression and antibacterial activity of epididymis protein 2 isoforms in the male reproductive tract of human and rhesus monkey (Macaca mulatta).
The epididymis protein 2 (EP2) gene, the fusion of two ancestral beta-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.
Avellar
Maria Christina W
MC
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. avellar@farm.epm.br
Honda
Luciana
L
Hamil
Katherine G
KG
Yenugu
Suresh
S
Grossman
Gail
G
Petrusz
Peter
P
French
Frank S
FS
Hall
Susan H
SH
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014644:Genetic Variation; D005837:Genitalia, Male / Q000378:metabolism*; D006020:Glycopeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015186:Hominidae / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014018:Tissue Distribution
D000900:Anti-Bacterial Agents; D000954:Antigens, Surface; D006020:Glycopeptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C087044:SPAG11A protein, human