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Epididymal Dysfunction Initiated by the Expression of Simian Virus 40 T-Antigen Leads to Angulated Sperm Flagella and Infertility in Transgenic Mice

Department of Physiology, Institute of Biomedicine (P.S., M.M., J.P., I.H., M.P.), and Turku Graduate School of Biomedical Sciences (P.S., J.P.), University of Turku, FIN-20520 Turku, Finland; Institute of Reproductive Medicine of the University (T.G.C., C.-H.Y.), D-48129 Münster, Germany; and Reproduction and Development Research Group (J.D.), Blaise Pascal University, Centre National de la Recherche Scientifique Unité Mixte de Recherche, F-63177 Aubière, France

Address all correspondence and requests for reprints to: Matti Poutanen, Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. E-mail: matti.poutanen{at}utu.fi.

We have generated two transgenic mouse lines (GPX5-Tag1 and GPX5-Tag2) by expressing the Simian virus 40 large and small T-antigens under a 5-kb promoter of the murine glutathione peroxidase 5 (GPX5) gene. In GPX5-Tag1 mice, with a high level of T-antigen expression, severe dysplasia was found in the epididymis and seminal vesicles. These mice also developed adrenal and prostate tumors, and spermatogenesis was disrupted. In GPX5-Tag2 mice, with a lower level of T-antigen expression, the only histological change was the slightly hyperplastic epithelium in the initial segment of the epididymidis and in the seminal vesicles. Despite normal mating behavior, these mice were infertile. The most conspicuous feature of the sperm was angulation of the flagellum, which appeared during epididymal transit, probably due to the observed reduction in the osmotic pressure of cauda epididymidal fluid. The angulation did not affect the motility or kinematic parameters of the sperm, but the sperm were also incapable of fertilization in vitro. The lack of expression of several genes specific for the initial segment suggests that in the GPX5-Tag2 mice the transgene expression brings about a differentiation arrest in this part of epididymis. This novel mouse line provides a model for epididymal dysfunction leading to defects in posttesticular sperm maturation and infertility.

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