Up-regulation of CD95 (Apo-1/Fas) is associated with spermatocyte apoptosis during the first round of spermatogenesis in the rat.
Apoptosis plays a major role in controlling both the rate of sperm production and chromosomal abnormalities in adult male testes. However, little is known on the mechanisms controlling induction and execution of apoptosis under physiological conditions. In this work we have uncovered a major role for the cell death receptor Fas in both the extrinsic and intrinsic pathways in normal germ cell apoptosis. We show here that Fas levels increased significantly in a group of germ cell in 25 d old rats, which were identified as spermatocytes and only a few spermatogonia. In addition, we show that isolated spermatocytes expressing high levels of Fas display activation of caspase-8, -9, -3, -6 and -2, as well as increased levels of intracellular calcium and decreased pH, which coincides with stabilization of p53, and transcriptional activation of PUMA and Fas. Therefore, our data strongly suggests that transcriptional up regulation of Fas could predispose a group of spermatocytes to Fas ligand triggering apoptosis by the extrinsic and intrinsic pathway.
Lizama
Carlos
C
Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda, 340, Santiago, Chile.
Alfaro
Iván
I
Reyes
Juan G
JG
Moreno
Ricardo D
RD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D020287:In Situ Nick-End Labeling; D008297:Male; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D019014:fas Receptor / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; C496337:Bard1 protein, rat; D044767:Ubiquitin-Protein Ligases; D020169:Caspases; D002118:Calcium