title: Differential permeability of the blood-testis barrier during reinitiation of spermatogenesis in adult male rats.
abstract: The blood-testis barrier (BTB) sequesters meiotic spermatocytes and differentiating spermatids away from the vascular environment. We aimed to assess whether meiosis and postmeiotic differentiation could occur when the BTB is permeable. Using a model of meiotic suppression and reinitiation, BTB function was assessed using permeability tracers of small, medium, and large (0.6-, 70-, and 150-kDa) sizes to emulate blood- and lymphatic-borne factors that could cross the BTB. Adult rats (n = 9/group) received the GnRH antagonist acyline (10 wk) to suppress gonadotropins, followed by testosterone (24cm Silastic implant), for 2, 4, 7, 10, 15, and 35 days. In acyline-suppressed testes, all tracers permeated the seminiferous epithelium. As spermatocytes up to diplotene stage XIII reappeared, both the 0.6- and 70-kDa tracers, but not 150 kDa, permeated around these cells. Intriguingly, the 0.6- and 70-kDa tracers were excluded from pachytene spermatocytes at stages VII and VIII but not in subsequent stages. The BTB became progressively impermeable to the 0.6- and 70-kDa tracers as stages IV-VII round spermatids reappeared in the epithelium. This coincided with the appearance of the tight junction protein, claudin-12, in Sertoli cells and at the BTB. We conclude that meiosis can occur when the BTB is permeable to factors up to 70 kDa during the reinitiation of spermatogenesis. Moreover, BTB closure corresponds with the presence of particular pachytene spermatocytes and round spermatids. This research has implications for understanding the effects of BTB dynamics in normal spermatogenesis and also potentially in states where spermatogenesis is suppressed, such as male hormonal contraception or infertility.
authors.affiliation: Prince Henry's Institute (J.T.H., S.J.M., P.K.N., K.E.R., E.R.S., P.G.S.), Monash Medical Centre, Clayton, VIC 3168, Australia; and Departments of Anatomy and Developmental Biology (J.T.H., S.J.M.) and Biochemistry and Molecular Biology (P.K.N., E.R.S., P.G.S.), Monash University, Clayton, VIC 3800, Australia.
authors.forename: Jenna T
authors.initials: JT
authors.lastname: Haverfield
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Meachem
authors.forename: Peter K
authors.initials: PK
authors.lastname: Nicholls
authors.forename: Katarzyna E
authors.initials: KE
authors.lastname: Rainczuk
authors.forename: Evan R
authors.initials: ER
authors.lastname: Simpson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stanton
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000502:physiology*; D057167:Claudins / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000378:metabolism; D009929:Organ Size; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000378:metabolism; D013087:Spermatids / Q000166:cytology; D013090:Spermatocytes / Q000166:cytology; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism; D019108:Tight Junctions; D013997:Time Factors
chemical_list: D057167:Claudins; D009842:Oligopeptides; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C109238:acyline