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Heat Shock Transcription Factor 1 Is Involved in Quality-Control Mechanisms in Male Germ Cells¹

Department of Biochemistry and Molecular Biology³ Department of Urology,⁴ Yamaguchi University School of Medicine, Ube 755-8505, Japan

Quality-control mechanisms in spermatogenesis are important to eliminate injured or abnormal cells, thereby protecting the organism from abnormal development in the next generation. The processes of spermatogenesis are highly sensitive to high temperatures; however, the mechanisms by which injured germ cells are eliminated remain unclear. Here, we found that heat shock proteins are not induced in male germ cells in response to thermal stress, although heat shock transcription factor 1 (HSF1) is activated. Using HSF1-null mice, we showed that apoptosis of pachytene spermatocytes was markedly inhibited in testes with a single exposure to heat and in the cryptorchid testes, indicating that HSF1 promotes apoptotic cell death of pachytene spermatocytes exposed to thermal stress. In marked contrast, HSF1 acts as a cell-survival factor of more immature germ cells, probably including spermatogonia, in testes exposed to high temperatures. These results demonstrate that HSF1 has two opposite roles in male germ cells independent of the activation of heat shock genes.

¹ Supported in part by Grants-in-Aid for Scientific Research and on Priority Areas "Life of Protein" and "Cancer" from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Naitoh Foundation; and Yamaguchi University Foundation.

² Correspondence: Akira Nakai, Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan. FAX: 81 836 22 2315; anakai{at}yamaguchi-u.ac.jp

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