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Partial Oxygen Pressure and Mitochondrial Permeability Transition Affect Germ Cell Apoptosis in the Human Testis¹

Hospital for Children and Adolescents, University of Helsinki (K.E., V.P., L.D.), FIN-00029 Helsinki, Finland; Helsinki Bioenergetics Group, Department of Medical Chemistry, Institute of Biomedical Sciences, University of Helsinki (M.W.), FIN-00014 Helsinki, Finland; and the Department of Anatomy, University of Turku (M.P.), FIN-20520 Turku, Finland

Address all correspondence and requests for reprints to: Dr. Krista Erkkilä, Hospital for Children and Adolescents, University of Helsinki, P.O. Box 281, Stenbäckinkatu 11, FIN-00029, HYKS (Helsinki), Finland. E-mail: krista.erkkila{at}huch.fi

During regular spermatogenesis, a number of testicular germ cells degenerate by an apoptotic process that is under hormonal control. Oxidative and mitochondrial changes have been proposed to play a role in apoptosis of many cell types. Previously, whether human germ cell survival is controlled by oxygen or by effectors of the mitochondrial permeability transition has not been investigated. In the present study, apoptosis was induced in human testicular germ cells by incubating segments of seminiferous tubules without survival factors (i.e. serum or hormones; 21% oxygen). Apoptosis was significantly suppressed in an inversely dose-dependent fashion at partial oxygen pressures below 10%, as detected by Southern blot analysis of DNA fragmentation, DNA labeling in situ, and electron microscopy. Cyclosporin A and its nonimmunosuppressive derivative N-methyl-Val⁴-cyclosporin A prevented cell death, suggesting a key role for the mitochondrial permeability transition in apoptosis. Apoptotic cells were identified as mainly spermatocytes and spermatids, the mitochondria of which underwent morphological changes during the apoptotic process. The present results imply that to improve germ cell viability in in vitro fertilization techniques, the partial oxygen pressure should be lowered.

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