title: Infertility in a transgenic rat due to impairment of cytoplasmic elimination and sperm release from the Sertoli cells.
abstract: In line TGR(mRen2)26 transgenic rats (TGR26) bearing a randomly inserted additional renin transgene, the males, but not the females, were found to be infertile. Tissue was obtained from TGR26 males and littermate controls after perfusion fixation, and the morphology of the testes and epididymides was examined. Testis size was normal as was gross morphology, but careful examination revealed that the release of many spermatozoa at stage IX of the spermatogenic cycle was impaired. In addition, the process of cytoplasmic elimination was abnormal, as cytoplasmic fragments of elongate spermatids were present in the epididymis. In TGR26 males, seminiferous tubule lumen size was significantly larger (p < 0.001) than in littermate controls, a difference that was most marked at stages IX-XIV--an effect that could be related to the retention of spermatozoa. In situ hybridization confirmed that expression of renin 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 transgene. Immunocytochemistry and in situ and Northern hybridization were used to elucidate the pattern of expression of genes that previous studies 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 cyclic protein 2[CP-2], none showed any major change in the pattern of expression compared with that in controls. We postulate that TGR26 transgenic male rats may be infertile because the expression of a gene (or genes) involved in the process of cytoplasmic elimination and/or sperm release has been disrupted by the presence of the transgene close to or within the gene(s). Future planned studies will involve determination of the insertion site(s) and ultrastructural analysis of the final phases of spermiogenesis.
authors.affiliation: MRC Reproductive Biology Unit, Edinburgh, United Kingdom.
authors.forename: R M
authors.initials: RM
authors.lastname: Sharpe
authors.forename: S M
authors.initials: SM
authors.lastname: Maguire
authors.forename: P T
authors.initials: PT
authors.lastname: Saunders
authors.forename: M R
authors.initials: MR
authors.lastname: Millar
authors.forename: L D
authors.initials: LD
authors.lastname: Russell
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: S
authors.initials: S
authors.lastname: Bachmann
authors.forename: L
authors.initials: L
authors.lastname: Mullins
authors.forename: J J
authors.initials: JJ
authors.lastname: Mullins
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D015152:Blotting, Northern; D003593:Cytoplasm / Q000502:physiology*; D004822:Epididymis / Q000648:ultrastructure; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012083:Renin / Q000235:genetics; D012708:Sertoli Cells / Q000648:ultrastructure*; D013094:Spermatozoa / Q000502:physiology*; D013737:Testis / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D012333:RNA, Messenger; D012083:Renin