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Interleukin 1 Alpha (IL1A) Is a Novel Regulator of the Blood-Testis Barrier in the Rat¹

Population Council,³ Center for Biomedical Research, New York, New York 10065 Department of Biochemistry and Molecular Biology,⁴ Pondicherry University, Puducherry 605 014, India

ABSTRACT

Throughout spermatogenesis, leptotene spermatocytes must traverse the blood-testis barrier (BTB) at stages VIII–XI to gain entry into the adluminal compartment for continued development. However, the mechanism underlying BTB restructuring remains somewhat elusive. In this study, interleukin 1 alpha (IL1A) was administered intratesticularly to adult rats in order to assess its effects on spermatogenesis. IL1A was shown to perturb Sertoli-germ cell adhesion, resulting in germ cell loss from 50% of seminiferous tubules by 15 days posttreatment. Equally important, the functional integrity of the BTB was compromised when inulin-fluorescein isothiocyanate was detected in the adluminal compartment of the seminiferous epithelium following its administration via the jugular vein. Interestingly, IL1A did not affect the steady-state levels of proteins that confer BTB function, namely OCLN, CLDN1, F11R, TJP1, and CDH2. Instead, the localizations of OCLN, F11R, and TJP1 in the seminiferous epithelium were altered; these proteins appeared to move away from sites of cell-cell contact. Moreover, IL1A was shown to perturb the orderly arrangement of filamentous actin at the BTB and apical ectoplasmic specialization with distinct areas illustrating loss of actin filaments. Taken collectively, these results suggest that IL1A-induced BTB disruption is not mediated via the reduction of target protein levels. Instead, IL1A's primary cellular target appears to be the Sertoli cell actin cytoskeleton. It is possible that localized production of IL1A by Sertoli and/or germ cells in vivo results in BTB restructuring, and this may facilitate the movement of leptotene spermatocytes across the BTB.

blood-testis barrier, cytoskeleton, ectoplasmic specialization, interleukin 1alpha (IL1A), testis, tight junction

¹Supported in part by grants from the CONRAD Program (CICCR, CIG-01-74) to D.D.M. and from the National Institutes of Health (NICHD, U54 HD029990 and U01 HD045908) to C.Y.C. Results reported herein were part of O.S.'s graduate studies performed in the laboratory of D.D.M. and submitted to Pondicherry University for the partial fulfillment of requirements for a Doctor of Philosophy degree.

Correspondence: ²FAX: 212 327 8733; e-mail: mruk{at}popcbr.rockefeller.edu