Study of Anti-apoptotic Effect of HST-1/FGF-4 on Spermatogenesis

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Apoptosis is a conserved biochemical suicide program that exists in most cells and is activated by a variety of normal developmental and pathogenic triggers. Apoptosis also plays an important role in controlling the number of male germ cells and eliminating defective germ cells during testicular development and spermatogenesis. Based on HST-1/FGF-4 conditional transgenic mice, we have previously shown that HST-1/FGF-4 may play a critical role as a survival factor for germ cells and protect them from apoptosis. To test this hypothesis, testes of adult male mice that received AxHST-1 or AxCAwt were exposed to mild hyperthermia, which causes germ cell apoptosis. The results indicated that induced expression of HST-1/FGF-4 significantly reduced the apoptotic death of spermatocytes, testicular weight decrease, and sperm count decrease. Finally, we showed that HST-1/FGF-4 triggered the p42/p44 MAP kianse signaling pathway in purified Sertoli cells, and stimulates those cells to induce lactate production, thereby leading to inhibition of germ cell apoptosis. These results suggest the participation of HST-1/FGF-4 in the complex network of intratesticular regulators and that HST-1/FGF-4-based gene therapy could present a new paradigm for male infertility.




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