Disorganization of claudin‐11 and dysfunction of the blood‐testis barrier during puberty in a cryptorchid rat model

Abstract

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.

Bibliometric and visual analysis of blood-testis barrier research

“…In another study ( Zhang L et al, 2021 ), the structure and function of anchoring junctions (AJs) in the testes of rats were discovered to be disturbed by VC. Loss of normal BTB function and decreased spermatogenesis have been found in undescended testes, suggesting that aberrant CLDN11 organization may induce undescended testes-associated male infertility ( Kato et al, 2020 ). An unhealthy lifestyle, characterized by, for example, consuming a high-fat diet leading to obesity, chronic stress, and lack of sleep, can also affect sperm quality through damage to the BTB.…”

E2F1 regulates testicular descent and controls spermatogenesis by influencing WNT4 signaling

“…contributing to spermatogenic failure (Kato et al, 2020). The cell-cell communications between the germ cells and Sertoli and Leydig cell compartments are important for spermatogenesis (Mruk and Cheng, 2004), and the altered cell-cell interaction in E2f1-null mice plays an important role in their testicular phenotype.…”

Excessive unilateral proliferation of spermatogonia in a patient with non-obstructive azoospermia – adverse effect of clomiphene citrate pre-treatment?

“…To further delineate Sertoli cell function, analysis of BTB components is mandatory [31]. One of the most commonly used techniques to assess BTB integrity are lanthanum tracer experiments [28,32,33], which require specialized tissue processing other than fixation with Bouin's solution. Instead, we employed immunohistochemistry for distinct proteins of the BTB.…”