活性氧被认为是导致癌症和衰老的元凶,还被视为男性不育的原因之一。但日本研究人员在动物实验中发现,如果体内活性氧不足,同样会导致不育。这是由于活性氧不足会导致精原干细胞难以增殖。
活性氧是氧气的同素异形体,其非常容易与其他物质发生反应,是一种强氧化剂。活性氧具有杀死病原菌等微生物的功能,但也会对细胞内的蛋白质等产生不良影响,引发阿尔茨海默氏症等疾病。
日本京都大学等机构的研究人员培养出实验鼠的精原干细胞,然后向干细胞添加抑制活性氧功能的药物,结果精原干细胞变得难以增殖。而如果向精原干细胞添加与实验鼠正常细胞相同浓度的活性氧,则精原干细胞的增殖得到促进。
研究小组指出,过剩的活性氧曾被认为会降低精子功能,导致不育,但是本项实验显示,活性氧不足也会引发男性不育。这个发现提供了治疗不育的新思路。
相关论文已刊登在新一期《细胞—干细胞》杂志上。(生物谷Bioon.com)
Cell Stem Cell DOI:10.1016/j.stem.2013.04.001
ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal
Hiroko Morimoto, Kazumi Iwata, Narumi Ogonuki, Kimiko Inoue, Ogura Atsuo, Mito Kanatsu-Shinohara, Takeshi Morimoto, Chihiro Yabe-Nishimura, Takashi Shinohara
Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesis as well as spermatogonial stem cells (SSCs). Using cultured SSCs, we show that ROS are generated via the AKT and MEK signaling pathways under conditions where the growth factors glial cell line-derived neurotrophic factor and fibroblast growth factor 2 drive SSC self-renewal and, instead, stimulate self-renewal at physiological levels. SSCs depleted of ROS stopped proliferating, but they showed enhanced self-renewal when ROS levels were increased by the addition of hydrogen peroxide, which induced the phosphorylation of stress kinases p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK). Moreover, ROS depletion in vivo decreased SSC number in the testis, and NADPH oxidase 1 (Nox1)-deficient SSCs exhibited reduced self-renewal division upon serial transplantation. These results suggest that ROS generated by Nox1 play critical roles in SSC self-renewal via the activation of the p38 MAPK and JNK pathways.