Rat GETM4, a Novel Germ Cell-Expressing Four-Transmembrane Protein Involved in Early Cleavage of Fertilized Ova.

Successful sperm-oocyte interactions are necessary for fertilization. Each of these process is mediated by the sperm head, probably through proteins both on the sperm surface and within the acrosome. In this study,We have isolated a novel Germ cell-enriched membrane gene in rat, ssp3111, and its protein designated GETM4. Reverse transcriptase (RT)-PCR and immunohistochemical analyses indicated that GETM4 is predominantly expressed from round spermatids to spermatozoa in rat testis at both the mRNA and protein levels. Immunofluorescence revealed that GETM4 is expressed in acrosome and midpiece of the flagellum in mature sperm. Interestingly, ssp3111 mRNA was also found in ovary, and GETM4 protein was found in membrane of mature oocyte and fertilized eggs by confocal immunofluorescence analysis. The predicted GETM4 protein contains 1,139 amino acids, consist four putative transmembrane domains and a glycoprotein domain. Polyclonal anti-GETM4 antibody Ab2438 does not inhibit in vitro fertilization, but the normal fertility rate declined to 15% compared to 90% in control group. Moreover, there were 68% oocytes were at >16-cell stage after 16-h fertilization if sperm pretreated with Ab2438. These results suggest that GETM4 might be a novel sperm surface antigen and its antibodies might interfere normal fertility through their enhancement of sperm-egg binding.