title: Seminiferous tubule fluid secretion is a Sertoli cell microtubule-dependent process inhibited by 2,5-hexanedione exposure.
abstract: Mammalian Sertoli cells are responsible for the formation and secretion of seminiferous tubule fluid (STF) which provides the nutritional and hormonal microenvironment necessary for spermatogenesis. Exposure of rats to 2,5-hexanedione (2,5-HD) results in testicular injury characterized by a decrease of STF secretion which immediately precedes bulk germ cell necrosis. The earliest biochemical change in 2,5-HD-exposed rats is an alteration in testicular microtubule assembly kinetics. In this study, we investigate the relationship between microtubule-dependent processes and STF secretion in adult Sprague-Dawley CD rats by exposing seminiferous tubules to two types of toxicants: (1) those which alter microtubules (colchicine and 2,5-HD) and (2) an inhibitor of protein secretion (brefeldin A, [BFA]). Secretion of STF is quantitated by monitoring the rate of transport of a microinjected oil droplet in the lumen of isolated seminiferous tubules using time-lapse stereoscopic microscopy. The rate of oil droplet transport in seminiferous tubules isolated from testis pretreated in vivo for 2 hr with colchicine (40 micrograms/testis) was significantly decreased. Exposure of isolated seminiferous tubules to BFA (10 micrograms/ml) for 40 min also significantly decreased the transport of lumenal oil droplets. Exposure of rats to 1%, 2,5-HD in drinking water decreased transport of injected oil droplets in seminiferous tubules beginning at 3 weeks of exposure in the absence of significant alterations in testicular morphology. These data demonstrate that normal STF secretion requires an intact, microtubule-dependent intracellular membrane transport pathway and strengthen the association between 2,5-HD-induced disruption of Sertoli cell STF secretion and 2,5-HD-induced alterations in Sertoli cell microtubules.
authors.affiliation: Department of Pathology, Brown University, Providence, Rhode Island 02912.
authors.forename: J H
authors.initials: JH
authors.lastname: Richburg
authors.forename: D M
authors.initials: DM
authors.lastname: Redenbach
authors.forename: K
authors.initials: K
authors.lastname: Boekelheide
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020126:Brefeldin A; D003078:Colchicine / Q000633:toxicity; D003517:Cyclopentanes / Q000633:toxicity; D006588:Hexanones / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D003517:Cyclopentanes; D006588:Hexanones; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; C011269:2,5-hexanedione; D003078:Colchicine