Altered hormonal milieu and dysregulated protein expression can cause spermatogenic arrest in ectopic xenografted immature rat testis
Altered hormonal milieu and dysregulated protein expression can cause spermatogenic arrest in ectopic xenografted immature rat testis
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DOI：
10.1038/s41598-019-40662-y
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发表时间：
2019-03-11
影响因子：
4.6
通讯作者：
Minami, Naojiro
中科院分区：
文献类型：
--
作者：
Goel, Sandeep;Minami, Naojiro
睾丸组织异种移植补充冷冻保存是一种可行的技术，为生育能力的保护儿童恶性肿瘤接受性腺毒性治疗和濒危物种的新生儿死亡率高。然而，人类和大多数濒危物种的异种移植睾丸已知会发生生精停滞。在这项研究中，我们异种移植未成熟的大鼠睾丸到免疫缺陷的雄性小鼠，以调查生精停滞的可能的根本原因。移植后8周收集的异种移植睾丸的组织学分析显示，精子发生不完全，粗面期精母细胞是最先进的生殖细胞。虽然受体小鼠血清促黄体生成素和睾酮水平正常，但卵泡刺激素（FSH）水平明显升高，且FSH特异性受体在异种移植物中缺失。异种移植物表现出支持细胞转录调节因子（WT 1和SOX 9）和分泌蛋白（SCF和GDNF）的表达失调。总之，我们的研究结果表明，受体的激素环境改变和异种移植物中蛋白质表达失调可能是异种移植未成熟大鼠睾丸生精障碍的潜在原因。异种移植物的进一步体视学分析可以证明异种移植物的精确细胞组成，以破译生殖细胞和体细胞之间的相互作用，从而更好地理解异种移植睾丸中的生精停滞。
Testis tissue xenografting complemented with cryopreservation is a feasible technique for fertility preservation in children with malignancy receiving gonadotoxic therapy and for endangered species with high neonatal mortality rate. However, xenografted testis of human and most endangered species are known to undergo spermatogenic arrest. In this study, we xenografted immature rat testis onto immunodeficient male mice to investigate the plausible underlying causes of spermatogenic arrest. Histological analysis of xenografted testes collected 8-wk post-grafting showed incomplete spermatogenesis with pachytene-stage spermatocytes as the most advanced germ cells. Although the levels of serum luteinizing hormone and testosterone were normal in recipient mice, those of follicle stimulating hormone (FSH) were significantly high, and specific receptors of FSH were absent in the xenografts. The xenografts demonstrated dysregulated expression of Sertoli cell-transcriptional regulators (WT1 and SOX9) and secretory proteins (SCF and GDNF). In conclusion, results from our study suggested that an altered hormonal milieu in recipients and dysregulated protein expression in xenografts could be a potential cause of spermatogenic arrest in xenografted immature rat testis. Further stereological analysis of xenografts can demonstrate precise cellular composition of xenografts to decipher interactions between germ and somatic cells to better understand spermatogenic arrest in xenografted testis.