Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
J Urol. 2015 Aug;194(2):585-91. doi: 10.1016/j.juro.2015.01.099. Epub 2015 Feb 2.
We examined the effects of long-term hCG stimulation on germ cell maturation, and Sertoli and Leydig cell function in a xenotransplantation model of the human fetal testis.
A total of 20 human fetal testes were ectopically xenografted on 20 castrated NCr male nude mice. Grafts were collected for analysis 24 weeks later. Mice were treated with saline as the control or with hCG beginning 4 weeks after the grafts were transplanted.
Of the grafts 65% survived at 24 weeks. In contrast to untreated pregrafted samples, hCG stimulated xenografts showed significantly increased density of seminiferous tubule formation with Sertoli cell migration to the basement membrane. Germ cell proliferation and differentiation from gonocytes (M2A(+)) to prespermatogonia (MAGE-4A(+)) were observed in graft samples recovered from the hCG and nonhCG treated groups at 24 weeks of treatment. Leydig cells in hCG treated grafts produced significantly more testosterone than nonhCG treated grafts. Although further studies are required to investigate the potential for further differentiation and maturation of xenografted human fetal testes, normal in utero testicular development was reproduced under long-term hCG stimulation.
This model represents a means to study long-term effects of gonadotoxins or hormonal stimulation on the maturation of human fetal testes.
我们研究了长期 hCG 刺激对人胎睾丸异种移植模型中生殖细胞成熟以及支持细胞和间质细胞功能的影响。
共将 20 个人胎睾丸异位异种移植到 20 只去势 NCr 雄性裸鼠体内。24 周后收集移植物进行分析。在移植后 4 周开始，用 hCG 或生理盐水处理小鼠作为对照。
24 周时，移植物中有 65%存活。与未经预处理的预移植样本相比，hCG 刺激的异种移植物显示出明显增加的生精小管形成密度，支持细胞向基膜迁移。在 hCG 和非 hCG 处理组的移植物样本中观察到从精原细胞（M2A(+））到精原细胞前体（MAGE-4A(+））的生殖细胞增殖和分化。hCG 处理的移植物中的间质细胞产生的睾酮明显多于非 hCG 处理的移植物。尽管需要进一步研究来探讨异种移植人胎睾丸进一步分化和成熟的潜力，但在长期 hCG 刺激下，正常的宫内睾丸发育得以重现。
该模型代表了一种研究性腺毒素或激素刺激对人胎睾丸成熟的长期影响的方法。
