Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation

Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation
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DOI:
10.1093/humrep/deq001
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发表时间:
2010-05-01
期刊:
影响因子:
6.1
通讯作者:
Iwamoto, T.
Iwamoto, T.
中科院分区:
医学1区
文献类型:
--
作者:
Sato, Y.;Nozawa, S.;Iwamoto, T.

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将睾丸组织移植到免疫缺陷小鼠中已用于区分不同动物物种的新生睾丸,直至达到完整精子发生的水平;然而,这种方法对于人类睾丸组织并不成功。本研究的目的是评估婴儿人睾丸组织移植物的分化能力。将3个月大的睾丸癌患者的睾丸组织移植到免疫缺陷的裸鼠体内。在移植时,A型精原细胞是睾丸组织中唯一的生殖细胞。分别于移植后7个月和1年观察B精原细胞和第一代精母细胞。用BOULE和CDC 25 A抗体的阳性免疫染色表明,移植物中的精母细胞没有被逮捕,但在减数分裂。此外,超微结构和免疫组化分析表明,支持细胞的成熟和部分分化的Leydig细胞的发病前精母细胞的外观。与体内发育相比,睾丸细胞的分化速度加快,从精原干细胞阶段到粗线期精母细胞形成,在异种移植的婴儿人睾丸组织中成功地进行了精子发生。支持细胞和间质细胞的分化以类似于正常睾丸发育的方式再现。婴儿睾丸组织移植可能是一个强有力的工具,以检查人类精子发生的早期阶段,并可能为婴儿患者的生育能力保存铺平道路。
Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts.Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development.Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.