Maturation of testicular tissue from infant monkeys after xenografting into mice
Maturation of testicular tissue from infant monkeys after xenografting into mice
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DOI：
10.1210/en.2008-0311
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发表时间：
2008-10-01
期刊：
影响因子：
4.8
通讯作者：
Dobrinski, Ina
中科院分区：
文献类型：
--
作者：
Rathi, Rahul;Zeng, Wenxian;Dobrinski, Ina
在幼龄猴中，性早熟可通过给予促性腺激素诱导，导致睾丸体细胞成熟和生殖细胞分化。然而，目前还不清楚睾丸成熟是否也可以在年轻的猴子中诱导。在这里，我们使用睾丸组织异种移植，以调查是否婴儿猴睾丸组织将进行体细胞成熟和/或精子发生的内源性成年小鼠促性腺激素或外源性促性腺激素。将来自3个月和6个月大的恒河猴的睾丸组织块移植到免疫缺陷的去势小鼠体内。移植后28周，将未处理或妊娠母马血清促性腺激素和/或人绒毛膜促性腺激素每周两次处理的BALB/c小鼠处死。根据形态学和存在的最高级生殖细胞类型以及增殖细胞核抗原、苗勒管抑制物质和雄激素受体表达的免疫组织化学评估移植组织中的睾丸成熟度。睾丸移植，无论供体年龄或治疗，含有较少的生殖细胞比供体组织。6个月大供体的移植物显示出小管扩张，生精小管直径增加，管腔形成，而从促性腺激素处理的小鼠中收获的移植物含有细长的精子细胞。从促性腺激素处理的小鼠中回收的3个月大供体的移植物含有粗线期精母细胞，而从未处理的小鼠中回收的移植物仅显示轻微的小管扩张。免疫组化显示，暴露于外源性促性腺激素支持细胞成熟，无论供体年龄。这些结果表明，持续的促性腺激素刺激未成熟（< 12个月大）的猴子睾丸支持支持细胞成熟，从而终止了生殖上皮的无反应期，并允许婴儿恒河猴睾丸组织中的完整精子发生。
In juvenile monkeys, precocious puberty can be induced by administration of gonadotropins resulting in testicular somatic cell maturation and germ cell differentiation. It is, however, unknown whether testicular maturation can also be induced in younger monkeys. Here we used testis tissue xenografting to investigate whether infant monkey testis tissue will undergo somatic cell maturation and/or spermatogenesis in response to endogenous adult mouse gonadotropins or exogenous gonadotropins. Testicular tissue pieces from 3- and 6-month-old rhesus monkeys were grafted to immunodeficient, castrated mice. Recipient mice were either left untreated or treated with pregnant mare serum gonadotropin and/or human chorionic gonadotropin twice weekly and were killed 28 weeks after grafting. Testicular maturation in grafted tissue was assessed based on morphology and the most advanced germ cell type present and by immunohistochemistry for expression of proliferating cell nuclear antigen, Mullerian-inhibiting substance, and androgen receptor. Testis grafts, irrespective of donor age or treatment, contained fewer germ cells than donor tissue. Grafts from 6-month-old donors showed tubular expansion with increased seminiferous tubule diameter and lumen formation, whereas those harvested from gonadotropin-treated mice contained elongated spermatids. Grafts from 3-month-old donors recovered from gonadotropin-treated mice contained pachytene spermatocytes, whereas those recovered from untreated mice showed only slight tubular expansion. Immunohistochemistry revealed that exposure to exogenous gonadotropins supported Sertoli cell maturation, irrespective of donor age. These results indicate that sustained gonadotropin stimulation of immature (< 12 months old) monkey testis supports Sertoli cell maturation, thereby terminating the unresponsive phase of the germinal epithelium and allowing complete spermatogenesis in testis tissue from infant rhesus monkeys.