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postgraduate thesis: Blood testis barrier: its biology and significance in spermatogenesis

TitleBlood testis barrier: its biology and significance in spermatogenesis
Authors
Advisors
Advisor(s):Lee, WWM
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Mok, K. [莫嘉維]. (2012). Blood testis barrier : its biology and significance in spermatogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979950
AbstractSpermatogenesis takes place in the seminiferous epithelium and it is a tightly regulated process that produces spermatozoa from spermatogonia. During spermatogenesis, germ cells have to traverse the seminiferous epithelium, from basal to adluminal compartment and finally reach the luminal edge of the seminiferous tubules at spermiation. During the transit of germ cells, they have to get across the blood-testis barrier (BTB), which is formed by adjacent Sertoli cells. Thus, although BTB is considered as one of the tightest blood-tissue barrier, the BTB undergoes cyclic restructuring to “open” transiently for the translocation of germ cells. However, the integrity of the BTB has to remain intact as the BTB is essential for the developing germ cells behind the barrier. For example, the BTB serves as an immunological barrier to “seal” developing germ cells from the systemic circulation. Since how the BTB restructuring is regulated remains elusive, the study herein aims to provide some information regarding to this events. The importance of the BTB to spermatogenesis was demonstrated by treating rats with 50 (lowdose) or 250 mg/kg b.w (high-dose) of adjudin. Although the BTB of rats was perturbed in both groups at week 6 post treatment, as shown by an in vivo BTB functional assay, the BTB of the low-dose group was found to have “resealed” at week 20 whereas the BTB of the high-dose group remained disrupted. Besides, despite almost all germ cells were depleted in both group of rats upon week 2 post treatment, spermatogonia were still present in the testis of rats no matter high- or low-dose of adjudin was used. However, spermatogenesis only recovered in low-dose treated group, which have an intact BTB. This suggests that after spermatogenesis is disrupted, its regeneration of spermatogenesis needs more than the existence of spermatogonia in which an intact BTB is required. After demonstrating the necessity of the BTB for spermatogenesis, the next question I addressed was how its restructuring was modulated. The involvement of mammalian target of rapamycin (mTOR) in manipulating the BTB was investigated. mTOR is able to form two distinct signaling complexes namely mTOR complex 1 (mTORC1) or mTORC2 by assembling with raptor or rictor, respectively. rpS6, which is a downstream molecule of mTORC1 was activated specifically during BTB restructuring and knockdown of rpS6 in cultured Sertoli cells was able to promote the TJ-barrier by inducing deposition of F-actin and BTB proteins at the cell-cell interface, suggesting the role of phosphorylated rpS6 is to “open” the BTB for the transit of spermatocytes. Moreover, the knockdown of rictor led to perturbation of TJ-barrier formed by cultured Sertoli cells via a PKC-α depending actin reorganization, causing internalization of BTB proteins. This indicates mTORC2 is necessary for the maintenance of the BTB and hence the two mTOR complexes work antagonistically to regulate the BTB in which mTORC1 is activated to promote the BTB restructuring while the expression of mTORC2 is essential to sustain the BTB integrity.
DegreeDoctor of Philosophy
SubjectSpermatogenesis in animals.
Testis - Physiology.
Dept/ProgramBiological Sciences

 

DC FieldValueLanguage
dc.contributor.advisorLee, WWM-
dc.contributor.authorMok, Ka-wai.-
dc.contributor.author莫嘉維.-
dc.date.issued2012-
dc.identifier.citationMok, K. [莫嘉維]. (2012). Blood testis barrier : its biology and significance in spermatogenesis. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979950-
dc.description.abstractSpermatogenesis takes place in the seminiferous epithelium and it is a tightly regulated process that produces spermatozoa from spermatogonia. During spermatogenesis, germ cells have to traverse the seminiferous epithelium, from basal to adluminal compartment and finally reach the luminal edge of the seminiferous tubules at spermiation. During the transit of germ cells, they have to get across the blood-testis barrier (BTB), which is formed by adjacent Sertoli cells. Thus, although BTB is considered as one of the tightest blood-tissue barrier, the BTB undergoes cyclic restructuring to “open” transiently for the translocation of germ cells. However, the integrity of the BTB has to remain intact as the BTB is essential for the developing germ cells behind the barrier. For example, the BTB serves as an immunological barrier to “seal” developing germ cells from the systemic circulation. Since how the BTB restructuring is regulated remains elusive, the study herein aims to provide some information regarding to this events. The importance of the BTB to spermatogenesis was demonstrated by treating rats with 50 (lowdose) or 250 mg/kg b.w (high-dose) of adjudin. Although the BTB of rats was perturbed in both groups at week 6 post treatment, as shown by an in vivo BTB functional assay, the BTB of the low-dose group was found to have “resealed” at week 20 whereas the BTB of the high-dose group remained disrupted. Besides, despite almost all germ cells were depleted in both group of rats upon week 2 post treatment, spermatogonia were still present in the testis of rats no matter high- or low-dose of adjudin was used. However, spermatogenesis only recovered in low-dose treated group, which have an intact BTB. This suggests that after spermatogenesis is disrupted, its regeneration of spermatogenesis needs more than the existence of spermatogonia in which an intact BTB is required. After demonstrating the necessity of the BTB for spermatogenesis, the next question I addressed was how its restructuring was modulated. The involvement of mammalian target of rapamycin (mTOR) in manipulating the BTB was investigated. mTOR is able to form two distinct signaling complexes namely mTOR complex 1 (mTORC1) or mTORC2 by assembling with raptor or rictor, respectively. rpS6, which is a downstream molecule of mTORC1 was activated specifically during BTB restructuring and knockdown of rpS6 in cultured Sertoli cells was able to promote the TJ-barrier by inducing deposition of F-actin and BTB proteins at the cell-cell interface, suggesting the role of phosphorylated rpS6 is to “open” the BTB for the transit of spermatocytes. Moreover, the knockdown of rictor led to perturbation of TJ-barrier formed by cultured Sertoli cells via a PKC-α depending actin reorganization, causing internalization of BTB proteins. This indicates mTORC2 is necessary for the maintenance of the BTB and hence the two mTOR complexes work antagonistically to regulate the BTB in which mTORC1 is activated to promote the BTB restructuring while the expression of mTORC2 is essential to sustain the BTB integrity.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B49799502-
dc.subject.lcshSpermatogenesis in animals.-
dc.subject.lcshTestis - Physiology.-
dc.titleBlood testis barrier: its biology and significance in spermatogenesis-
dc.typePG_Thesis-
dc.identifier.hkulb4979950-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineBiological Sciences-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4979950-
dc.date.hkucongregation2013-

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