Institute of Reproductive and Regenerative Biology, Centre of Reproductive Medicine and Andrology, University of Münster, Domagkstrasse 11, 48149 Münster, Germany.
Reproduction. 2010 Nov;140(5):733-42. doi: 10.1530/REP-10-0235. Epub 2010 Aug 20.
The seminiferous epithelium in the nonhuman primate Callithrix jacchus is similarly organized to man. This monkey has therefore been used as a preclinical model for spermatogenesis and testicular stem cell physiology. However, little is known about the developmental dynamics of germ cells in the postnatal primate testis. In this study, we analyzed testes of newborn, 8-week-old, and adult marmosets employing immunohistochemistry using pluripotent stem cell and germ cell markers DDX4 (VASA), POU5F1 (OCT3/4), and TFAP2C (AP-2γ). Stereological and morphometric techniques were applied for quantitative analysis of germ cell populations and testicular histological changes. Quantitative RT-PCR (qRT-PCR) of testicular mRNA was applied using 16 marker genes establishing the corresponding profiles during postnatal testicular development. Testis size increased during the first 8 weeks of life with the main driver being longitudinal outgrowth of seminiferous cords. The number of DDX4-positive cells per testis doubled between birth and 8 weeks of age whereas TFAP2C- and POU5F1-positive cells remained unchanged. This increase in DDX4-expressing cells indicates dynamic growth of the differentiated A-spermatogonial population. The presence of cells expressing POU5F1 and TFAP2C after 8 weeks reveals the persistence of less differentiated germ cells. The mRNA and protein profiles determined by qRT-PCR and western blot in newborn, 8-week-old, and adult marmosets corroborated the immunohistochemical findings. In conclusion, we demonstrated the presence of distinct spermatogonial subpopulations in the primate testis exhibiting different dynamics during early testicular development. Our study demonstrates the suitability of the marmoset testis as a model for human testicular development.
非人类灵长类动物 Callithrix jacchus 的生精上皮组织与人类相似。因此,这种猴子被用作精子发生和睾丸干细胞生理学的临床前模型。然而,对于出生后灵长类动物睾丸中生殖细胞的发育动态知之甚少。在这项研究中,我们使用多能干细胞和生殖细胞标志物 DDX4(VASA)、POU5F1(OCT3/4)和 TFAP2C(AP-2γ)对新生、8 周龄和成年狨猴的睾丸进行了免疫组织化学分析。我们应用体视学和形态计量学技术对生殖细胞群体和睾丸组织学变化进行定量分析。应用 16 个标记基因的睾丸 mRNA 定量 RT-PCR(qRT-PCR)建立了出生后睾丸发育过程中的相应图谱。睾丸大小在生命的前 8 周内增加,主要驱动力是生精索的纵向生长。睾丸中每个 DDX4 阳性细胞的数量在出生到 8 周龄之间增加了一倍,而 TFAP2C 和 POU5F1 阳性细胞保持不变。DDX4 表达细胞的这种增加表明分化的 A 精原细胞群体的动态生长。8 周后表达 POU5F1 和 TFAP2C 的细胞的存在揭示了较少分化的生殖细胞的持续存在。qRT-PCR 和 Western blot 确定的 mRNA 和蛋白质图谱证实了新生、8 周龄和成年狨猴的免疫组织化学发现。总之,我们证明了在灵长类动物睾丸中存在不同的精原细胞亚群,它们在早期睾丸发育过程中表现出不同的动力学。我们的研究表明,狨猴睾丸适合作为人类睾丸发育的模型。