Kido Tatsuo, Arata Satoru, Suzuki Ryusuke, Hosono Tomohiko, Nakanishi Yoshinobu, Miyazaki Jun-ichi, Saito Izumu, Kuroki Toshio, Shioda Seiji
Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Dev Growth Differ. 2005 Jan;47(1):15-24. doi: 10.1111/j.1440-169x.2004.00775.x.
The quality control of sperm is critical for efficient reproduction. In germ cells, cell death involves different processes to those in somatic cells, and in many cases, the trigger to induce cell death in deficient germ cells is still unclear. It is known that the fatty acid composition of sperm is related to fertility. Composition of the fatty acid of germ cells changes dynamically during spermatogenesis, and fatty acid binding protein (FABP) may be involved in these changes. In this study, we developed transgenic mice with a testicular germ-cell-specific FABP (PERF15) transgene, whose expression was controlled by the Cre-LoxP site-specific recombination system. We also developed transgenic mice with the Cre gene under the control of the spermatocyte specific Pgk2 promoter. In double transgenic mice, following Cre-mediated recombination of the PERF15 containing transgene, PERF15 was strongly overexpressed. Its overexpression induced multinucleate symplasts to form, indicating programmed germ cell death occurred at the elongated spermatid stage. As a result, sperm harboring the transgene were significantly decreased, but the surviving sperm demonstrated higher fertility than natural sperm. Therefore, we conclude that PERF15 associate with the direction of germ cell fates and preserve the quality of sperm.
精子的质量控制对于高效繁殖至关重要。在生殖细胞中，细胞死亡涉及与体细胞不同的过程，而且在许多情况下，诱导缺陷生殖细胞死亡的触发因素仍不清楚。已知精子的脂肪酸组成与生育能力有关。生殖细胞的脂肪酸组成在精子发生过程中动态变化，脂肪酸结合蛋白（FABP）可能参与这些变化。在本研究中，我们构建了睾丸生殖细胞特异性FABP（PERF15）转基因小鼠，其表达由Cre-LoxP位点特异性重组系统控制。我们还构建了在精母细胞特异性Pgk2启动子控制下带有Cre基因的转基因小鼠。在双转基因小鼠中，Cre介导含PERF15的转基因重组后，PERF15强烈过表达。其过表达诱导多核共生体形成，表明在延长型精子细胞阶段发生了程序性生殖细胞死亡。结果，携带转基因的精子显著减少，但存活的精子显示出比天然精子更高的生育能力。因此，我们得出结论，PERF15与生殖细胞命运的走向相关并维持精子质量。
