Disorganization of claudin-11 and dysfunction of the blood-testis barrier during puberty in a cryptorchid rat model.
blood-testis barrier
claudin-11
cryptorchidism
spermatogenesis
tight junction
undescended testis
Journal
Andrology
ISSN: 2047-2927
Titre abrégé: Andrology
Pays: England
ID NLM: 101585129
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
06
06
2019
revised:
12
03
2020
accepted:
15
03
2020
pubmed:
21
3
2020
medline:
10
8
2021
entrez:
21
3
2020
Statut:
ppublish
Résumé
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). To determine the role of BTB during puberty in UDT using a non-surgical cryptorchid rat model. 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. 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. 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. CLDN11 disorganization within the BTB may cause spermatogenic impairment, possibly by limiting the BTB function.
Sections du résumé
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.
Substances chimiques
Claudins
0
Cldn11 protein, rat
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1398-1408Informations de copyright
© 2020 American Society of Andrology and European Academy of Andrology.
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