Mitchell R T, Cowan G, Morris K D, Anderson R A, Fraser H M, Mckenzie K J, Wallace W H B, Kelnar C J H, Saunders P T K, Sharpe R M
MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, The Queen's Medical Research Institute, Edinburgh, Scotland, UK.
Hum Reprod. 2008 Dec;23(12):2755-65. doi: 10.1093/humrep/den295. Epub 2008 Aug 11.
Testicular germ cell tumours (TGCT) are thought to originate from fetal germ cells that fail to differentiate normally, but no animal model for these events has been described. We evaluated the marmoset (Callithrix jacchus) as a model by comparing perinatal germ cell differentiation with that in humans.
Immunohistochemical profiling was used to investigate germ cell differentiation (OCT4, NANOG, AP-2gamma, MAGE-A4, VASA, NANOS-1) and proliferation (Ki67) in fetal and neonatal marmoset testes in comparison with the human and, to a lesser extent, the rat.
In marmosets and humans, differentiation of gonocytes into spermatogonia is associated with the gradual loss of pluripotency markers such as OCT4 and NANOG, and the expression of germ cell-specific proteins such as VASA. This differentiation occurs asynchronously within individual cords during fetal and early postnatal life. This contrasts with rapid and synchronous germ cell differentiation within and between cords in the rat. Similarly, germ cell proliferation in the marmoset and human occurs throughout perinatal life, in contrast to rats in which proliferation ceases during this period.
The marmoset provides a good model for normal human germ cell differentiation and proliferation. The perinatal marmoset may be a useful model in which to establish factors that lead to failure of normal germ cell differentiation and the origins of TGCT.
睾丸生殖细胞肿瘤(TGCT)被认为起源于未能正常分化的胎儿生殖细胞,但尚未有针对这些事件的动物模型被描述。我们通过比较围产期生殖细胞分化与人类的情况,评估狨猴(Callithrix jacchus)作为一种模型。
采用免疫组织化学分析方法,将胎儿和新生儿狨猴睾丸中的生殖细胞分化(OCT4、NANOG、AP - 2γ、MAGE - A4、VASA、NANOS - 1)和增殖(Ki67)情况与人类进行比较,并在较小程度上与大鼠进行比较。
在狨猴和人类中,生殖母细胞向精原细胞的分化与多能性标志物如OCT4和NANOG的逐渐丧失以及生殖细胞特异性蛋白如VASA的表达相关。这种分化在胎儿期和出生后早期的单个索状结构内异步发生。这与大鼠中索状结构内和之间的生殖细胞快速同步分化形成对比。同样,狨猴和人类的生殖细胞增殖在整个围产期都存在,而大鼠在此期间增殖停止。
狨猴为正常人类生殖细胞分化和增殖提供了一个良好的模型。围产期狨猴可能是一个有用的模型,可用于确定导致正常生殖细胞分化失败的因素以及TGCT的起源。