Impaired gap junction Connexin43 in Sertoli cells of patients with secretory azoospermia:: A marker of undifferentiated Sertoli cells
Impaired gap junction Connexin43 in Sertoli cells of patients with secretory azoospermia:: A marker of undifferentiated Sertoli cells
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DOI：
10.1097/01.lab.0000059928.82702.6d
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发表时间：
2003-03-01
影响因子：
5
通讯作者：
Pointis, G
中科院分区：
文献类型：
--
作者：
Defamie, N;Berthaut, I;Pointis, G
缝隙连接是由相邻细胞之间的质膜上的连接蛋白(Cx)形成的细胞间通道，参与了细胞增殖和分化的调控。CX表达的改变与几种人类疾病和肿瘤的发生密切相关。虽然Cx43在支持细胞控制精子发生中起着关键作用，但没有证据表明它在人类睾丸病理中的表达发生了变化。我们的研究表明，分泌性无精子症不育患者(p<；0.05)的Cx43基因表达显著低于正常生精(排泄性无精子症患者)患者。在单纯支持细胞综合征中，原位杂交和免疫组织化学分析显示Cx43mRNA和蛋白在支持细胞中未检测到，但仍存在于间质中。在仅支持细胞综合征的大鼠模型中，支持细胞中Cx43的缺失与相邻支持细胞之间的缝隙连接细胞间通讯受损有关。这些结果表明，不育症患者支持细胞中Cx43mRNA和蛋白的表达明显受损。这种缺陷可能是未分化支持细胞的一个新的功能标志，并可能与最近在不育男性人群中描述的睾丸癌风险增加有关。
Gap junctions are intercellular channels formed of connexins (Cx) at appositional plasma membranes between adjacent cells that have been involved in the control of cell proliferation and differentiation. Altered Cx expression is implicated consistently in several human diseases and in tumorigenesis. Although Cx43 plays a critical role in Sertoli cell control of spermatogenesis, there is no evidence of its altered expression in human testicular pathologies. We show here that Cx43 mRNA expression was significantly reduced in testes of infertile patients with secretory azoospermia (p < 0.05) compared with testes displaying normal spermatogenesis (excretory azoospermic patients). In Sertoli cell-only syndrome, in situ hybridization and immunohistochemistry analyses indicated that Cx43 mRNA and protein were undetectable in Sertoli cells but were still present in the interstitial compartment. In a rat model of Sertoli cell-only syndrome, the lack of Cx43 in Sertoli cells was associated with an impairment of gap junction intercellular communication between adjacent Sertoli cells. These results reveal that Cx43 mRNA and protein expression are markedly impaired in Sertoli cells of infertile patients. This defect could be a new functional marker of undifferentiated Sertoli cells and could be related to the increased risk of testicular cancer recently described in the population of infertile men.