Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model
Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model
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DOI：
10.1111/andr.12788
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发表时间：
2020-04-13
期刊：
影响因子：
4.5
通讯作者：
Yasui, Takahiro
中科院分区：
文献类型：
--
作者：
Kato, Taiki;Mizuno, Kentaro;Yasui, Takahiro
背景隐睾症是众所周知的损害精子发生。血睾屏障（BTB）在青春期左右在曲细精管中形成，为生殖细胞提供合适的环境。鲜为人知的是BTB在隐睾（UDT）。目的确定BTB在青春期UDT的作用，使用非手术隐睾大鼠model.Material和方法单侧隐睾雄性大鼠腹腔注射非甾体类抗雄激素在宫内发育过程中，睾丸在出生后4，5，6周收获。睾丸组织学，表达水平的BTB蛋白（claudin-11，occludin，zonula occludens-1），和凋亡细胞进行了评价，免疫组化，蛋白质印迹，和TUNEL法。结果出生后6周的未降睾丸组织学检查显示，BTB在精母细胞水平出现成熟阻滞。BTB蛋白分布在UDT中发生改变，在对照和UDT样品之间，出生后4至5周的紧密连接蛋白-11（CLDN 11）定位存在显著差异。BTB蛋白水平相似。与对照组相比，UDT组的睾丸小管近腔室中检测到更多的凋亡生殖细胞。电子显微镜检查表明，镧示踪剂仅限于BTB的控制睾丸，而它渗透BTB的UDT.Discussion在这里，正常的BTB功能的损失和受损的精子发生在青春期的UDT观察。CLDN 11是属于BTB的关键紧密连接蛋白。紧密连接被认为是正常精子发生所必需的，而CLDN 11的异常组织化可能导致UDT相关的男性不育。结论BTB内CLDN 11的紊乱可能通过限制BTB功能而导致生精障碍。
Background Cryptorchidism is known to impair spermatogenesis. The blood-testis barrier (BTB) becomes defined in seminiferous tubules around puberty and provides a suitable environment for germ cells. Little is known about the BTB in undescended testes (UDT).Objectives To determine the role of BTB during puberty in UDT using a non-surgical cryptorchid rat model.Material and Methods Unilateral cryptorchid male rats were intraperitoneally injected with non-steroidal antiandrogen during intrauterine development; the testes were harvested at 4, 5, and 6 weeks after birth. Testicular histology, expression levels of the BTB proteins (claudin-11, occludin, zonula occludens-1), and apoptotic cells were evaluated by immunohistochemistry, Western blotting, and TUNEL assay. The functionality of the BTB was investigated by electron microscopy using the lanthanum tracer method.Results The testicular histology of undescended testes 6 weeks after birth showed maturation arrest at the spermatocyte level. The BTB protein distributions were altered in the UDT, with a noticeable difference in claudin-11(CLDN11) localization from 4 to 5 weeks after birth between control and UDT samples. BTB protein levels were similar. More apoptotic germ cells were detected in the adluminal compartment of tubules in the UDT than in the control testes. Electron microscopy showed that the lanthanum tracer was limited to the BTB of control testes, whereas it penetrated the BTB of UDT.Discussion Here, loss of normal BTB function and impaired spermatogenesis were observed in UDT during puberty. CLDN11 is a pivotal tight junction protein belonging to the BTB. Tight junctions are considered as essential for normal spermatogenesis, and abnormal CLDN11 organization may cause UDT-associated male infertility.Conclusion CLDN11 disorganization within the BTB may cause spermatogenic impairment, possibly by limiting the BTB function.