Interleukin 1 Alpha (IL1A) is a novel regulator of the blood-testis barrier in the rat
Sarkar,Oli; Mathur,Premendu P.; Cheng,Chuen-yan; Mruk,Dolores D.
Biology of Reproduction 78(3): 445-454
Publication date: 2008
Throughout spermatogenesis, leptotene spermatocytes must traversethe blood-testis barrier (BTB) at stages VIII-XI to gainentry into the adluminal compartment for continued development.However, the mechanism underlying BTB restructuring remainssomewhat elusive. In this study, interleukin 1 alpha (IL1A)was administered intratesticularly to adult rats in order toassess its effects on spermatogenesis. IL1A was shown to perturbSertoli-germ cell adhesion, resulting in germ cell loss from50% of seminiferous tubules by 15 days posttreatment. Equallyimportant, the functional integrity of the BTB was compromisedwhen inulin-fluorescein isothiocyanate was detected in the adluminalcompartment of the seminiferous epithelium following its administrationvia the jugular vein. Interestingly, IL1A did not affect thesteady-state levels of proteins that confer BTB function, namelyOCLN, CLDN1, F11R, TJP1, and CDH2. Instead, the localizationsof OCLN, F11R, and TJP1 in the seminiferous epithelium werealtered; these proteins appeared to move away from sites ofcell-cell contact. Moreover, IL1A was shown to perturb the orderlyarrangement of filamentous actin at the BTB and apical ectoplasmicspecialization with distinct areas illustrating loss of actinfilaments. Taken collectively, these results suggest that IL1A-inducedBTB disruption is not mediated via the reduction of target proteinlevels. Instead, IL1A's primary cellular target appears to bethe Sertoli cell actin cytoskeleton. It is possible that localizedproduction of IL1A by Sertoli and/or germ cells in vivo resultsin BTB restructuring, and this may facilitate the movement ofleptotene spermatocytes across the BTB.