Xia Weiliang, Wong Ching Hang, Lee Nikki P Y, Lee Will M, Cheng C Yan
Population Council, New York, New York 10021, USA.
J Cell Physiol. 2005 Oct;205(1):141-57. doi: 10.1002/jcp.20377.
During spermatogenesis, both adherens junctions (AJ) (such as ectoplasmic specialization (ES), a testis-specific AJ type at the Sertoli cell-spermatid interface (apical ES) or Sertoli-Sertoli cell interface (basal ES) in the apical compartment and BTB, respectively) and tight junctions (TJ) undergo extensive restructuring to permit germ cells to move across the blood-testis barrier (BTB) as well as the seminiferous epithelium from the basal compartment to the luminal edge to permit fully developed spermatids (spermatozoa) to be sloughed at spermiation. However, the integrity of the BTB cannot be compromised throughout spermatogenesis so that postmeiotic germ cell-specific antigens can be sequestered from the systemic circulation at all times. We thus hypothesize that AJ disruption in the seminiferous epithelium unlike other epithelia, can occur without compromising the BTB-barrier, even though these junctions, namely TJ and basal ES, co-exist side-by-side in the BTB. Using an intratesticular androgen suppression-induced germ cell loss model, we have shown that the disruption of AJs indeed was limited to the Sertoli-germ cell interface without perturbing the BTB. The testis apparently is using a unique physiological mechanism to induce the production of both TJ- and AJ-integral membrane proteins and their associated adaptors to maintain BTB integrity yet permitting a transient loss of cell adhesion function by dissociating N-cadherin from beta-catenin at the apical and basal ES. The enhanced production of TJ proteins, such as occludin and ZO-1, at the BTB site can supersede the transient loss of cadherin-catenin function at the basal ES. This thus allows germ cell depletion from the epithelium without compromising BTB integrity. It is plausible that the testis is using this novel mechanism to facilitate the movement of preleptotene and leptotene spermatocytes across the BTB at late stage VIII through early stage IX of the epithelial cycle in the rat while maintaining the BTB immunological barrier function.
在精子发生过程中，黏着连接（AJ，如顶端外质特化（ES），分别为顶端小室内支持细胞 - 精子细胞界面（顶端ES）或支持细胞 - 支持细胞界面（基部ES）处的一种睾丸特异性AJ类型，以及血 - 睾屏障（BTB））和紧密连接（TJ）都会经历广泛的结构重组，以允许生殖细胞穿过血 - 睾屏障以及从基部小室到管腔边缘的生精上皮，从而使完全发育的精子细胞（精子）在精子释放时脱落。然而，在整个精子发生过程中，血 - 睾屏障的完整性不能受到损害，以便减数分裂后生殖细胞特异性抗原始终能与体循环隔离开来。因此，我们推测，与其他上皮不同，生精上皮中的AJ破坏可能在不损害血 - 睾屏障的情况下发生，尽管这些连接，即TJ和基部ES，在血 - 睾屏障中并排存在。使用睾丸内雄激素抑制诱导的生殖细胞丢失模型，我们已经表明，AJ的破坏确实仅限于支持细胞 - 生殖细胞界面，而不会干扰血 - 睾屏障。睾丸显然正在利用一种独特的生理机制来诱导TJ和AJ整合膜蛋白及其相关衔接蛋白的产生，以维持血 - 睾屏障的完整性，同时通过在顶端和基部ES处使N - 钙黏蛋白与β - 连环蛋白解离，允许细胞黏附功能的短暂丧失。TJ蛋白（如闭合蛋白和ZO - 1）在血 - 睾屏障部位的产生增加可以取代基部ES处钙黏蛋白 - 连环蛋白功能的短暂丧失。这从而允许上皮中的生殖细胞减少，而不损害血 - 睾屏障的完整性。很可能睾丸正在利用这种新机制来促进前细线期和细线期精母细胞在大鼠上皮周期的VIII期末到IX期早期穿过血 - 睾屏障，同时维持血 - 睾屏障的免疫屏障功能。
