Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy.
Differentiating male germ cells express a testis-specific form of cytochrome c (Cyt c(T)) that is distinct from the cytochrome c expressed in somatic cells (Cyt c(S)). To examine the role of Cyt c(T) in germ cells, we generated mice null for Cyt c(T). Homozygous Cyt c(T)(-/-) pups were statistically underrepresented (21%) but developed normally and were fertile. However, spermatozoa isolated from the cauda epididymis of Cyt c(T)-null animals were less effective in fertilizing oocytes in vitro and contain reduced levels of ATP compared to wild-type sperm. Sperm from Cyt c(T)-null mice contained a greater number of immotile spermatozoa than did samples from control mice, i.e., 53.1% +/- 13.7% versus 33.2% +/- 10.3% (P < 0.0001) for vas deferens sperm and 40.1% +/- 9.6% versus 33.2% +/- 7.5% (P = 0.0104) for epididymal sperm. Cyt c(T)-null mice often exhibit early atrophy of the testes after 4 months of age, losing germ cells as a result of increased apoptosis. However, no difference in the activation of caspase-3, -8, or -9 was detected between the Cyt c(T)(-/-) testes and controls. Our data indicate that the Cyt c(T)-null testes undergo early atrophy equivalent to that which occurs during aging as a consequence of a reduction in oxidative phosphorylation.
Narisawa
Sonoko
S
The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Hecht
Norman B
NB
Goldberg
Erwin
E
Boatright
Kelly M
KM
Reed
John C
JC
Millán
José Luis
JL
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001284:Atrophy / Q000235:genetics* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000172:deficiency* / Q000235:genetics; D045304:Cytochromes c; D005298:Fertility / Q000235:genetics; D005306:Fertilization; D006019:Glycolysis; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009929:Organ Size; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D017386:Sequence Homology, Amino Acid; D013081:Sperm Motility; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology*; D013733:Testicular Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013737:Testis / Q000201:enzymology* / Q000473:pathology
D003574:Cytochrome c Group; C461499:testis-specific cytochrome c, mouse; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D020169:Caspases