INFERTILITY IN A TRANSGENIC RAT DUE TO IMPAIRMENT OF CYTOPLASMIC ELIMINATION AND SPERM RELEASE FROM THE SERTOLI CELLS (VOL 53, PG 214, 1995)

In line TGR(mRen2)26 transgenic rats (TGR26) bearing a randomly insert ed additional renin transgene, the males, but not the females, were fo und to be infertile. Tissue was obtained from TGR26 males and litterma te controls after perfusion fixation, and the morphology of the testes and epididymides was examined. Testis size was normal as was gross mo rphology, but careful examination revealed that the release of many sp ermatozoa at stage IX of the spermatogenic cycle was impaired, In addi tion, the process of cytoplasmic elimination was abnormal, as cytoplas mic fragments of elongate spermatids were present in the epididymis, i n TGR26 males, seminiferous tubule lumen size was significantly larger (p < 0.001) than in littermate controls, a difference that was most m arked at stages IX-XIV-an effect that could be related to the retentio n of spermatozoa. In situ hybridization confirmed that expression of r enin mRNA could be detected in testes of TGR26 rats but not in normal controls or in a fertile line (TGR27) of rats bearing the same transge ne, Immunocytochemistry and in situ and Northern hybridization were us ed to elucidate the pattern of expression of genes that previous studi es have implicated in the process of sperm maturation and/or release, Of the gene products examined (sulphated glycoproteins 1 and 2 [SGP-1, SGP-2], transition proteins 1 and 2 [TP-1, TP-2], urokinase, and cycl ic protein 2 [CP-2]), none showed any major change in the pattern of e xpression compared with that in controls. We postulate that TGR26 tran sgenic male rats may be infertile because the expression of a gene (or genes) involved in the process of cytoplasmic elimination and/or sper m release has been disrupted by the presence of the transgene close to or within the gene(s). Future planned studies will involve determinat ion of the insertion site(s) and ultrastructural analysis of the final phases of spermiogenesis.