抑制特发性非梗阻性无精子症中内源性促性腺激素的高水平可改善精子发生：一项病例对照初步研究。
Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study.
机构信息
Center of Reproductive Medicine, Nanjing Jinling Hospital, the Medical School of Nanjing University, Nanjing, 210002, China.
Nanjing Jiangning Hospital, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, 210000, China.
出版信息
Reprod Biol Endocrinol. 2018 Sep 22;16(1):91. doi: 10.1186/s12958-018-0401-7.
BACKGROUND
Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear.
METHODS
Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective.
RESULTS
A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution.
CONCLUSIONS
Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02544191 .
背景
升高的血浆促性腺激素与睾丸内支持细胞和间质细胞的脱敏有关。通过抑制严重少精子症患者的内源性高促性腺激素，可以改善睾丸生精功能。但对于非阻塞性无精子症（NOA）患者是否有益仍不清楚。
方法
促性腺激素释放激素激动剂（GnRHα）戈舍瑞林用于抑制 NOA 患者的内源性促性腺激素水平（性腺激素重置），从而提高支持细胞和间质细胞的敏感性。然后注射人绝经期促性腺激素（hMG）和人绒毛膜促性腺激素（hCG）刺激它们以改善睾丸生精能力。主要观察指标是精液中是否存在精子或通过睾丸精子提取（TESE）获得精子。抑制素 B 的升高和/或 ZO-1 的改善表达模式为次要观察指标。
结果
共纳入 35 名经 TESE 未能获取精子的 NOA 男性患者。其中，未治疗的 10 例患者作为对照组，6 个月后进行二次 TESE。25 例治疗患者中，11 例在第 4 周内抑制素 B 升高（反应组），而在接下来的 20 周内只有 5 例持续升高（反应组 2）。这 5 名患者中，有 2 名获得精子（反应组 2B），3 名未获得精子（反应组 2A）。免疫荧光法检测小鼠同源物（MVH）和 ZO-1 发现，反应组 2 的阳性 MVH 信号和 ZO-1 表达均显著增加，但仅反应组 2B 显示出改善的 ZO-1 分布。
结论
促性腺激素重置是一种新的治疗方案，使用 GnRHα 可以通过恢复 Sertoli 和 Leydig 细胞的敏感性来改善 NOA 患者的睾丸生精功能，这反映在抑制素 B 的升高和 ZO-1 表达和分布的改善上。
试验注册
ClinicalTrials.gov 标识符：NCT02544191。
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