Mol. Hum. Reprod. Advance Access originally published online on August 6, 2004
Molecular Human Reproduction 2004 10(10):743-753; doi:10.1093/molehr/gah094
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Activator protein-1 in human male germ cell apoptosis
1Programme for Developmental and Reproductive Biology, Biomedicum Helsinki and Hospital for Children and Adolescents, University of Helsinki, FIN-00029, Helsinki, 2Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, FIN-00014, Helsinki, 3Wihuri Research Institute, Helsinki, 4Department of Urology, Helsinki University Central Hospital, Helsinki, and 5Kuopio University Central Hospital, Kuopio, Finland
6 To whom correspondence should be addressed at: Hospital for Children and Adolescents, University of Helsinki, Biomedicum Helsinki, Haartmaninkatu 8, 5 krs B529b, PO Box 700, FIN-00029, Helsinki, Finland. Email: laura.suomalainen{at}hus.fi
Apoptosis limits germ cell number in the testis, and its dysregulation is associated with male infertility. Here, we evaluated the role of the transcription factor activator protein 1 (AP-1) in male germ cell apoptosis in a culture of human seminiferous tubules. AP-1 DNA-binding activity increased in cultured tubules within 2.5 h, which was earlier than the onset of apoptosis as detected by caspase 3 activation and apoptotic DNA fragmentation. The c-Jun, c-Fos and JunD proteins were detected in the Sertoli cell nuclei, whereas apoptosis occurred in the germ cells. Follicle-stimulating hormone (FSH), whose receptors are expressed in the Sertoli cells, inhibited germ cell apoptosis and concomitantly suppressed AP-1 DNA-binding activity, but had no effect on nuclear factor 
B (NF-B) activation. These results suggest that AP-1 transcription factors are involved in the Sertoli cell-mediated control of germ cell apoptosis, and that inhibition of germ cell apoptosis by FSH appears to involve suppression of AP-1 activation.
Key words: apoptosis/germ cells/Sertoli cells/signal transduction/spermatogenesis
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