Blockage of the rete testis and efferent ductules by ectopic Sertoli and Leydig cells causes infertility in Dax1-deficient male mice
Blockage of the rete testis and efferent ductules by ectopic Sertoli and Leydig cells causes infertility in Dax1-deficient male mice
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DOI：
10.1210/en.142.10.4486
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发表时间：
2001-10-01
期刊：
影响因子：
4.8
通讯作者：
Russell, LD
中科院分区：
文献类型：
--
作者：
Jeffs, B;Meeks, JJ;Russell, LD
DAX-1。转录因子孤儿核受体超家族的 X 连锁成员，在性别决定和性腺分化中发挥关键作用。尽管血清 T 和促性腺激素水平正常，但缺乏 Dax1 的雄性小鼠不育且睾丸较小。对 Dax1 缺陷睾丸的检查显示，生精小管扩张，精子受精能力参数异常，这与睾丸可能阻塞的情况一致。为了验证这一假设，我们对 Dax1 缺陷小鼠的雄性生殖道进行了全面评估。光学和电子显微镜检查显示，睾丸网被位置异常的支持细胞阻塞，在睾丸中形成坏死精子的尾部。支持细胞还阻塞近端和中段传出导管，这伴随着传出导管上皮的过度生长。靠近睾丸网的生精小管含有异位间质细胞，与间质中存在的增生性间质细胞不同。这些小管周围的管周组织经常异常，含有相对未分化的肌样细胞，并且肌样细胞和支持细胞之间没有基底膜。三分之一的老年（>1 岁）缺乏 Dax1 的雄性小鼠会出现性索间质肿瘤，这些肿瘤源自支持细胞/颗粒细胞或 Leydig 细胞谱系的细胞。综合起来，这些观察结果揭示了 Dax1 缺陷的雄性小鼠中 Leydig 细胞和 Sertoli 细胞的异常分化和增殖，导致睾丸网阻塞和不育。
DAX-1. an X-linked member of the orphan nuclear receptor superfamily of transcription factors, plays a key role in sex determination and gonadal differentiation. Dax1-deficient male mice are infertile and have small testes despite normal serum levels of T and gonadotropins. Examination of Dax1-deficient testes reveals dilated seminiferous tubules and abnormal parameters of sperm fertilizing capability consistent with a possible obstruction in the testis. To test this hypothesis, we performed a comprehensive evaluation of the male reproductive tract in Dax1-deficient mice. Light and electron microscopic examination revealed the rete testis is blocked by aberrantly located Sertoli cells, creating a tailback of necrosing sperm in the testis. Sertoli cells also obstruct the proximal and middle efferent ductules, and this is accompanied by an overgrowth of the efferent duct epithelium. Seminiferous tubules close to the rete testis contain ectopic Leydig cells, distinct from the hyperplastic Leydig cells present in the interstitial space. The peritubular tissue surrounding these tubules is frequently abnormal, containing relatively undifferentiated myoid cells and no basement membrane between the myoid cells and Sertoli cells. A third of aged (>1-yr-old) Dax1-deficient male mice develop sex cord-stromal tumors, derived from cells of the Sertoli/granulosa cell or Leydig cell lineages. Combined, these observations reveal abnormal differentiation and proliferation of Leydig cells and Sertoli cells in Dax1-deficient male mice, leading to obstruction of the rete testis and infertility.