Department of Clinical and Experimental Medicine, Section of Pharmacology, Toxicology, and Chemotherapy, Medical School, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
J Biol Chem. 2012 Jan 6;287(2):1242-51. doi: 10.1074/jbc.M111.316372. Epub 2011 Nov 22.
Correct function of spermatogonia is critical for the maintenance of spermatogenesis throughout life, but the cellular pathways regulating undifferentiated spermatogonia proliferation, differentiation, and survival are only partially known. We show here that long glucocorticoid-induced leucine zipper (L-GILZ) is highly expressed in spermatogonia and primary spermatocytes and controls spermatogenesis. Gilz deficiency in knock-out (gilz KO) mice leads to a complete loss of germ cell lineage within first cycles of spermatogenesis, resulting in male sterility. Spermatogenesis failure is intrinsic to germ cells and is associated with increased proliferation and aberrant differentiation of undifferentiated spermatogonia and with hyperactivity of Ras signaling pathway as indicated by an increase of ERK and Akt phosphorylation. Spermatogonia differentiation does not proceed beyond the prophase of the first meiotic division due to massive apoptosis associated with accumulation of unrepaired chromosomal damage. These results identify L-GILZ as a novel important factor for undifferentiated spermatogonia function and spermatogenesis.
精原细胞的正常功能对于终生维持精子发生至关重要，但调控未分化精原细胞增殖、分化和存活的细胞途径尚不完全清楚。我们在此表明，长糖皮质激素诱导亮氨酸拉链（L-GILZ）在精原细胞和初级精母细胞中高度表达，并调控精子发生。敲除（gilz KO）小鼠的 Gilz 缺失导致精子发生的前几个周期内完全丧失生殖细胞谱系，导致雄性不育。生殖细胞衰竭是内在的，与未分化精原细胞的过度增殖和异常分化以及 Ras 信号通路的过度活跃有关，这表现为 ERK 和 Akt 磷酸化的增加。由于与未修复的染色体损伤积累相关的大量细胞凋亡，精原细胞的分化无法进行到第一次减数分裂的前期。这些结果表明 L-GILZ 是未分化精原细胞功能和精子发生的一个新的重要因素。
