Es-slami S, Charcellay S, Pinon-Lataillade G, Soufir J C
Groupe de Recherche en Urologie, Université Paris XI, Le Kremlin-Bicêtre, France.
Cancer. 1999 Mar 15;85(6):1313-22.
Hormonal treatments lasting 2-6 months inhibit spermatogenesis in men and have been proposed as germ cell protection against anticancer therapy. Because it is unthinkable to delay anticancer treatments, the authors investigated the protection afforded against irradiation of rats by 22 days of hormonal pretreatment.
Adult Sprague-Dawley rats were assigned to an untreated control group (C) or to one of 5 treatments: medroxyprogesterone acetate plus testosterone only (M), 3 or 5 gray of irradiation (R3 and R5), or hormonal treatment prior to 3 or 5 gray of irradiation (MR3 and MR5). Mating trials were conducted 1, 24, 45, 65, 86, and 109 days after treatment. At 122 days, genital organ weights, testis histology, and epididymal spermatozoa were evaluated.
Irradiation reduced sperm production and had a clastogenic effect on postmeiotic germ cells. No protective effect of steroid treatment was observed. Moreover, testis weight, tubule diameter, the repopulating index, and the sperm head count decreased more in the MR5 group than in the R5 group. Mating tests showed decreases in positive vaginal smears and fertility at both 45 and 65 days, and an increase in resorption at 109 days.
These results indicate that hormonal pretreatment potentiates irradiation damage to germ cells, especially stem cells, as regards survival and genomic alterations, probably because of increased lipoperoxidation of late spermatids.
持续2至6个月的激素治疗会抑制男性精子生成,并且已被提议作为针对抗癌治疗的生殖细胞保护措施。由于延迟抗癌治疗是不可想象的,因此作者研究了22天的激素预处理对大鼠辐射的保护作用。
将成年Sprague-Dawley大鼠分为未处理的对照组(C)或5种处理组之一:仅使用醋酸甲羟孕酮加睾酮(M)、3或5格雷辐射(R3和R5),或在3或5格雷辐射前进行激素治疗(MR3和MR5)。在治疗后1、24、45、65、86和109天进行交配试验。在122天时,评估生殖器官重量、睾丸组织学和附睾精子。
辐射减少了精子产生,并对减数分裂后生殖细胞有染色体断裂效应。未观察到类固醇治疗的保护作用。此外,MR5组的睾丸重量、曲细精管直径、再生指数和精子头部计数比R5组下降得更多。交配试验显示,在45天和65天时阳性阴道涂片和生育力下降,在109天时吸收增加。
这些结果表明,激素预处理在生殖细胞存活和基因组改变方面增强了辐射对生殖细胞尤其是干细胞的损伤,这可能是由于晚期精子细胞脂质过氧化增加所致。