Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Andrology. 2013 Nov;1(6):886-98. doi: 10.1111/j.2047-2927.2013.00126.x. Epub 2013 Sep 30.
Hormone suppression given before or after cytotoxic treatment stimulates the recovery of spermatogenesis from endogenous and transplanted spermatogonial stem cells (SSC) and restores fertility in rodents. To test whether the combination of hormone suppression and transplantation could enhance the recovery of spermatogenesis in primates, we irradiated (7 Gy) the testes of 12 adult cynomolgus monkeys and treated six of them with gonadotropin-releasing hormone antagonist (GnRH-ant) for 8 weeks. At the end of this treatment, we transfected cryopreserved testicular cells with green fluorescent protein-lentivirus and autologously transplanted them back into one of the testes. The only significant effect of GnRH-ant treatment on endogenous spermatogenesis was an increase in the percentage of tubules containing differentiated germ cells (tubule differentiation index; TDI) in the sham-transplanted testes of GnRH-ant-treated monkeys compared with radiation-only monkeys at 24 weeks after irradiation. Although transplantation alone after irradiation did not significantly increase the TDI, detection of lentiviral DNA in the spermatozoa of one radiation-only monkey indicated that some transplanted cells colonized the testis. However, the combination of transplantation and GnRH-ant clearly stimulated spermatogenic recovery as evidenced by several observations in the GnRH-ant-treated monkeys receiving transplantation: (i) significant increases (~20%) in the volume and weight of the testes compared with the contralateral sham-transplanted testes and/or to the transplanted testes of the radiation-only monkeys; (ii) increases in TDI compared to the transplanted testes of radiation-only monkeys at 24 weeks (9.6% vs. 2.9%; p = 0.05) and 44 weeks (16.5% vs. 6.1%, p = 0.055); (iii) detection of lentiviral sequences in the spermatozoa or testes of five of the GnRH-ant-treated monkeys and (iv) significantly higher sperm counts than in the radiation-only monkeys. Thus hormone suppression enhances spermatogenic recovery from transplanted SSC in primates and may be a useful tool in conjunction with spermatogonial transplantation to restore fertility in men after cancer treatment.
在细胞毒性治疗之前或之后给予激素抑制可刺激内源性和移植的精原干细胞（SSC）的生精恢复，并恢复啮齿动物的生育能力。为了测试激素抑制和移植的组合是否可以增强灵长类动物生精恢复，我们用（7Gy）照射 12 只成年食蟹猴的睾丸，并对其中 6 只进行促性腺激素释放激素拮抗剂（GnRH-ant）治疗 8 周。在治疗结束时，我们用绿色荧光蛋白慢病毒转染冷冻保存的睾丸细胞，并将其自体移植回一只睾丸中。GnRH-ant 治疗对内生精的唯一显著影响是，与仅接受辐射的猴子相比，在照射后 24 周，GnRH-ant 治疗的假移植睾丸中的包含分化生殖细胞的小管百分比（小管分化指数；TDI）增加。尽管单独进行移植后不会显著增加 TDI，但在一只仅接受辐射的猴子的精子中检测到慢病毒 DNA 表明，一些移植细胞定植在睾丸中。然而，移植和 GnRH-ant 的组合显然刺激了生精恢复，这可以从接受移植的 GnRH-ant 治疗的猴子的几个观察结果中得到证明：（i）与对侧假移植睾丸和/或仅接受辐射的猴子的移植睾丸相比，睾丸的体积和重量显著增加（~20%）；（ii）与仅接受辐射的猴子的移植睾丸相比，24 周（9.6%对 2.9%；p=0.05）和 44 周（16.5%对 6.1%，p=0.055）时 TDI 增加；（iii）在五名 GnRH-ant 治疗的猴子的精子或睾丸中检测到慢病毒序列；（iv）精子计数明显高于仅接受辐射的猴子。因此，激素抑制可增强灵长类动物中移植的 SSC 的生精恢复，并且可能是与精原细胞移植结合使用以恢复癌症治疗后男性生育能力的有用工具。
