title: Disruption of Sertoli-germ cell adhesion function in the seminiferous epithelium of the rat testis can be limited to adherens junctions without affecting the blood-testis barrier integrity: an in vivo study using an androgen suppression model.
abstract: During spermatogenesis, both adherens junctions (AJ) (such as ectoplasmic specialization (ES), a testis-specific AJ type at the Sertoli cell-spermatid interface (apical ES) or Sertoli-Sertoli cell interface (basal ES) in the apical compartment and BTB, respectively) and tight junctions (TJ) undergo extensive restructuring to permit germ cells to move across the blood-testis barrier (BTB) as well as the seminiferous epithelium from the basal compartment to the luminal edge to permit fully developed spermatids (spermatozoa) to be sloughed at spermiation. However, the integrity of the BTB cannot be compromised throughout spermatogenesis so that postmeiotic germ cell-specific antigens can be sequestered from the systemic circulation at all times. We thus hypothesize that AJ disruption in the seminiferous epithelium unlike other epithelia, can occur without compromising the BTB-barrier, even though these junctions, namely TJ and basal ES, co-exist side-by-side in the BTB. Using an intratesticular androgen suppression-induced germ cell loss model, we have shown that the disruption of AJs indeed was limited to the Sertoli-germ cell interface without perturbing the BTB. The testis apparently is using a unique physiological mechanism to induce the production of both TJ- and AJ-integral membrane proteins and their associated adaptors to maintain BTB integrity yet permitting a transient loss of cell adhesion function by dissociating N-cadherin from beta-catenin at the apical and basal ES. The enhanced production of TJ proteins, such as occludin and ZO-1, at the BTB site can supersede the transient loss of cadherin-catenin function at the basal ES. This thus allows germ cell depletion from the epithelium without compromising BTB integrity. It is plausible that the testis is using this novel mechanism to facilitate the movement of preleptotene and leptotene spermatocytes across the BTB at late stage VIII through early stage IX of the epithelial cycle in the rat while maintaining the BTB immunological barrier function.
authors.affiliation: Population Council, New York, New York 10021, USA.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
authors.forename: Ching Hang
authors.initials: CH
authors.lastname: Wong
authors.forename: Nikki P Y
authors.initials: NP
authors.lastname: Lee
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D001814:Blood-Testis Barrier / Q000502:physiology*; D001835:Body Weight; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D023421:Models, Animal; D062793:Occludin; D009929:Organ Size; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000166:cytology* / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin
chemical_list: D000728:Androgens; D015820:Cadherins; D015815:Cell Adhesion Molecules; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D019000:Phosphotyrosine