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Mol. Hum. Reprod. Advance Access published online on August 6, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah094
© 2004 by Oxford University Press
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Received April 27, 2004
Revised June 22, 2004
Accepted July 11, 2004

Article

Activator protein-1 in human male germ cell apoptosis

Laura Suomalainen 1*, Leo Dunkel 2, Ilkka Ketola 1, Minna Eriksson 3, Krista Erkkilä 1, Riina Oksjoki 4, Kimmo Taari 5, Markku Heikinheimo 1, Virve Pentikäinen 1

1 Programme for Developmental and Reproductive Biology, Biomedicum Helsinki and Hospital for Children and Adolescents, University of Helsinki, FIN-00029, Helsinki, , Finland
2 Kuopio University Central Hospital, Kuopio, Finland
3 Molecular Cancer Biology Research Program, Biomedicum Helsinki, University of Helsinki, FIN-00014, Helsinki, , Finland
4 Wihuri Research Institute, Helsinki, , Finland
5 Department of Urology, Helsinki University Central Hospital, Helsinki,, Finland

* To whom correspondence should be addressed. E-mail: laura.suomalainen{at}hus.fi.


  Abstract

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 {kappa}B (NF-{kappa}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.

Keywords: apoptosis; germ cells; Sertoli cells; signal transduction; spermatogenesis.
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