Catizone A, Ricci G, Del Bravo J, Galdieri M
Department of Histology and Medical Embryology, School of Medicine, University of Rome La Sapienza, Rome, Italy.
J Endocrinol. 2006 Apr;189(1):137-46. doi: 10.1677/joe.1.06528.
The hepatocyte growth factor (HGF) is a pleiotropic cytokine that influences mitogenesis, motility and differentiation of many different cell types by its tyrosine kinase receptor c-Met. We previously demonstrated that the c-Met/HGF system is present and functionally active during postnatal testis development. We found also that spermatozoa express c-Met and that HGF has a positive effect on the maintenance of sperm motility. In the present paper, we extend our study on the germ cells at different stages of differentiation during the postnatal development of the testis. We demonstrate that c-met is present in rat spermatogonia, pachytene spermatocytes and round spermatids and that HGF significantly increases spermatogonial proliferation in 8- to 10-day-old pre-pubertal rats. At this age HGF does not affect Sertoli cells and peritubular myoid cells proliferation. In addition, we studied the effect of the factor on germ cell apoptosis and we show that HGF prevents the germ cell apoptotic process. We also studied the effect of HGF on 18- to 20-day-old and 28- to 30-day-old rat testes. At these ages also the factor significantly increases germ cell duplication and decreases the number of apoptotic cells. However, the effect on programmed cell death is higher in the 8- to 10-day-old rats and declines in the older animals. In conclusion, we report that rat germ cells (spermatogonia, pachytene spermatocytes and round spermatids) express c-met and that HGF modulates germ cell proliferating activity and apoptosis in vitro. These data indicate that the c-Met/HGF system is involved in male germ cell homeostasis and, consequently, has a role in male fertility.
肝细胞生长因子（HGF）是一种多效性细胞因子，它通过其酪氨酸激酶受体c-Met影响多种不同细胞类型的有丝分裂、运动和分化。我们之前证明了c-Met/HGF系统在出生后睾丸发育过程中存在且功能活跃。我们还发现精子表达c-Met，并且HGF对精子活力的维持有积极作用。在本文中，我们扩展了对睾丸出生后发育过程中不同分化阶段生殖细胞的研究。我们证明c-met存在于大鼠精原细胞、粗线期精母细胞和圆形精子细胞中，并且HGF显著增加8至10日龄青春期前大鼠的精原细胞增殖。在这个年龄，HGF不影响支持细胞和睾丸肌样细胞的增殖。此外，我们研究了该因子对生殖细胞凋亡的影响，结果表明HGF可防止生殖细胞凋亡过程。我们还研究了HGF对18至20日龄和28至30日龄大鼠睾丸的影响。在这些年龄，该因子也显著增加生殖细胞复制并减少凋亡细胞数量。然而，对程序性细胞死亡的影响在8至10日龄大鼠中更高，在年龄较大的动物中则下降。总之，我们报告大鼠生殖细胞（精原细胞、粗线期精母细胞和圆形精子细胞）表达c-met，并且HGF在体外调节生殖细胞增殖活性和凋亡。这些数据表明c-Met/HGF系统参与雄性生殖细胞稳态，因此在雄性生育中发挥作用。
