Blood Testis Barrier

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C. Yan Cheng - One of the best experts on this subject based on the ideXlab platform.

  • Modulating the Blood-Testis Barrier Towards Increasing Drug Delivery.
    Trends in pharmacological sciences, 2020
    Co-Authors: Baiping Mao, Dolores D. Mruk, Fei Sun, C. Yan Cheng
    Abstract:

    Testicular cells produce several biologically active peptides that exert their downstream effects by activating distinct signaling proteins. These biomolecules are now known to support spermatogenesis and effectively enhance paracellular and transcellular diffusion of drugs (e.g., adjudin) across the BloodTestis Barrier (BTB). We briefly discuss the biomolecules that maintain the BTB: these provide new insights into how the BTB can be modulated to allow therapeutic drugs, including male contraceptives, to be transported across the BTB and more generally across Blood–tissue Barriers. Information gleaned by studying the BTB, as well as other Blood–tissue Barriers, augments our understanding of Blood–tissue Barriers and provides new insights into how drugs can be delivered to organs that are effectively protected by tissue Barriers.

  • mTORC1/rpS6 regulates Blood-Testis Barrier dynamics and spermatogenetic function in the Testis in vivo.
    American journal of physiology. Endocrinology and metabolism, 2017
    Co-Authors: Ming Yan, Tito T. Jesus, Haiqi Chen, Xiang Xiao, Will M. Lee, C. Yan Cheng
    Abstract:

    The Blood-Testis Barrier (BTB), conferred by Sertoli cells in the mammalian Testis, is an important ultrastructure that supports spermatogenesis. Studies using animal models have shown that a disru...

  • mTORC1/rpS6 regulates Blood-Testis Barrier (BTB) dynamics and spermatogenetic function in the Testis in vivo
    American Journal of Physiology-endocrinology and Metabolism, 2017
    Co-Authors: Stephen Y.t. Li, Tito T. Jesus, Haiqi Chen, Xiang Xiao, C. Yan Cheng
    Abstract:

    The Blood-Testis Barrier (BTB), conferred by Sertoli cells in the mammalian Testis, is an important ultrastructure that supports spermatogenesis. Studies using animal models have shown that a disru...

  • The Mammalian Blood-Testis Barrier: Its Biology and Regulation
    Endocrine Reviews, 2015
    Co-Authors: Dolores D. Mruk, C. Yan Cheng
    Abstract:

    Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian Testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the Blood-Testis Barrier. The Blood-Testis Barrier, one of the tightest tissue Barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The Blood-Testis Barrier is different from most other tissue Barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the Blood-Testis Barrier. More recent studies have defined the regulatory mechanisms that underlie Blood-Testis Barrier function. We review here the biology and regulation of the mammalian Blood-Testis Barrier and highlight research areas that should be expanded in future studies.

  • Actin binding proteins in BloodTestis Barrier function
    Current Opinion in Endocrinology Diabetes and Obesity, 2015
    Co-Authors: Nan Li, Dolores D. Mruk, C. Yan Cheng
    Abstract:

    Purpose of review This review examines the role of actin binding proteins (ABPs) on Blood-Testis Barrier (BTB), an androgen-dependent ultrastructure in the Testis, in particular their involvement on BTB remodeling during spermatogenesis.

Dolores D. Mruk - One of the best experts on this subject based on the ideXlab platform.

  • Modulating the Blood-Testis Barrier Towards Increasing Drug Delivery.
    Trends in pharmacological sciences, 2020
    Co-Authors: Baiping Mao, Dolores D. Mruk, Fei Sun, C. Yan Cheng
    Abstract:

    Testicular cells produce several biologically active peptides that exert their downstream effects by activating distinct signaling proteins. These biomolecules are now known to support spermatogenesis and effectively enhance paracellular and transcellular diffusion of drugs (e.g., adjudin) across the BloodTestis Barrier (BTB). We briefly discuss the biomolecules that maintain the BTB: these provide new insights into how the BTB can be modulated to allow therapeutic drugs, including male contraceptives, to be transported across the BTB and more generally across Blood–tissue Barriers. Information gleaned by studying the BTB, as well as other Blood–tissue Barriers, augments our understanding of Blood–tissue Barriers and provides new insights into how drugs can be delivered to organs that are effectively protected by tissue Barriers.

  • Annexin A2 is critical for Blood-Testis Barrier integrity and spermatid disengagement in the mammalian Testis
    Biochimica et Biophysica Acta, 2016
    Co-Authors: Katarzyna Chojnacka, Barbara Bilińska, Dolores D. Mruk
    Abstract:

    Abstract Throughout spermatogenesis, two important processes occur at late stage VIII of the seminiferous epithelial cycle in the rat Testis: preleptotene spermatocytes commence entry into the adluminal compartment and step 19 spermatids release from the seminiferous epithelium. Presently, it is not clear how these processes, which involve extensive restructuring of unique Sertoli–Sertoli and Sertoli–germ cell junctions, are mediated. We aimed to determine whether annexin A2 (ANXA2), a Ca 2 + -dependent and phospholipid-binding protein, participates in cell junction dynamics. To address this, in vitro and in vivo RNA interference studies were performed on prepubertal Sertoli cells and adult rat testes. The endpoints of Anxa2 knockdown were determined by immunoblotting, morphological analyses, fluorescent immunostaining, and Barrier integrity assays. In the Testis, ANXA2 localized to the Sertoli cell stalk, with specific staining at the BloodTestis Barrier and the concave (ventral) surface of elongated spermatids. ANXA2 also bound actin when Testis lysates were used for immunoprecipitation. Anxa2 knockdown was found to disrupt the Sertoli cell/BloodTestis Barrier in vitro and in vivo. The disruption in Barrier function was substantiated by changes in the localization of claudin-11, zona occludens-1, N-cadherin, and β-catenin. Furthermore, Anxa2 knockdown resulted in spermiation defects caused by a dysfunction of tubulobulbar complexes, Testis-specific actin-rich ultrastructures that internalize remnant cell junction components prior to spermiation. Additionally, there were changes in the localization of several tubulobulbar complex component proteins, including actin-related protein 3, cortactin, and dynamin I/II. Our results indicate that ANXA2 is critical for the integrity of the BloodTestis Barrier and the timely release of spermatids.

  • Emergent roles for intercellular adhesion molecule-1 in the restructuring of the Blood-Testis Barrier during spermatogenesis in the mammal.
    Histology and Histopathology, 2015
    Co-Authors: Dolores D. Mruk
    Abstract:

    Mammalian spermatogenesis is comprised of a series of molecular, cellular, and morphological events that underscore the movement of developing germ cells across the Blood-Testis Barrier. These events involve the restructuring of tight junctions, basal ectoplasmic specializations, gap junctions, and desmosomes, which constitute Blood-Testis Barrier function. Previous studies show that preleptotene/leptotene spermatocytes traverse the Blood-Testis Barrier while transiently trapped within an intermediate compartment, which sequesters primary spermatocytes away from basal and adluminal compartments of the seminiferous epithelium. Preleptotene/leptotene spermatocytes enter the adluminal compartment when stable junctions ahead of spermatocytes disassemble, while new junctions assemble behind them. While there is enormous restructuring of the seminiferous epithelium, the mechanism of germ cell movement is incompletely understood. In this perspective, the significance of intercellular adhesion molecule-1 in the restructuring of the Blood-Testis Barrier during spermatogenesis in the mammal is discussed

  • The Mammalian Blood-Testis Barrier: Its Biology and Regulation
    Endocrine Reviews, 2015
    Co-Authors: Dolores D. Mruk, C. Yan Cheng
    Abstract:

    Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian Testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the Blood-Testis Barrier. The Blood-Testis Barrier, one of the tightest tissue Barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The Blood-Testis Barrier is different from most other tissue Barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the Blood-Testis Barrier. More recent studies have defined the regulatory mechanisms that underlie Blood-Testis Barrier function. We review here the biology and regulation of the mammalian Blood-Testis Barrier and highlight research areas that should be expanded in future studies.

  • actin binding proteins in Blood Testis Barrier function
    Current Opinion in Endocrinology Diabetes and Obesity, 2015
    Co-Authors: Dolores D. Mruk, Yan C Cheng
    Abstract:

    Purpose of review This review examines the role of actin binding proteins (ABPs) on Blood-Testis Barrier (BTB), an androgen-dependent ultrastructure in the Testis, in particular their involvement on BTB remodeling during spermatogenesis.

Yolanda I Chirino - One of the best experts on this subject based on the ideXlab platform.

  • Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and BloodTestis Barrier disruption in mice
    Journal of Applied Toxicology, 2019
    Co-Authors: Juan Carlos Rodríguez-escamilla, Estefany I. Medina-reyes, Carolina Rodríguez-ibarra, Alejandro Déciga-alcaraz, José O. Flores-flores, Adriana Ganem-rondero, Miriam Rodriguez-sosa, Norma L. Delgado-buenrostro, Luis Ignacio Terrazas, Yolanda I Chirino
    Abstract:

    : Food-grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to Bloodstream, which could disturb Barriers such as the Blood-Testis Barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and Blood-Testis Barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on Testis structure, inflammation infiltrate and Blood-Testis Barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the Blood-Testis Barrier were similar in Testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on Testis when E171 is consumed in a liquid matrix.

  • Food-grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and Blood-Testis Barrier disruption in mice.
    Journal of Applied Toxicology, 2019
    Co-Authors: Juan Carlos Rodríguez-escamilla, Estefany I. Medina-reyes, Carolina Rodríguez-ibarra, Alejandro Déciga-alcaraz, José O. Flores-flores, Adriana Ganem-rondero, Miriam Rodriguez-sosa, Norma L. Delgado-buenrostro, Luis Ignacio Terrazas, Yolanda I Chirino
    Abstract:

    Food-grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to Bloodstream, which could disturb Barriers such as the Blood-Testis Barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and Blood-Testis Barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on Testis structure, inflammation infiltrate and Blood-Testis Barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the Blood-Testis Barrier were similar in Testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on Testis when E171 is consumed in a liquid matrix.

Juan Carlos Rodríguez-escamilla - One of the best experts on this subject based on the ideXlab platform.

  • Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and BloodTestis Barrier disruption in mice
    Journal of Applied Toxicology, 2019
    Co-Authors: Juan Carlos Rodríguez-escamilla, Estefany I. Medina-reyes, Carolina Rodríguez-ibarra, Alejandro Déciga-alcaraz, José O. Flores-flores, Adriana Ganem-rondero, Miriam Rodriguez-sosa, Norma L. Delgado-buenrostro, Luis Ignacio Terrazas, Yolanda I Chirino
    Abstract:

    : Food-grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to Bloodstream, which could disturb Barriers such as the Blood-Testis Barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and Blood-Testis Barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on Testis structure, inflammation infiltrate and Blood-Testis Barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the Blood-Testis Barrier were similar in Testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on Testis when E171 is consumed in a liquid matrix.

  • Food-grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and Blood-Testis Barrier disruption in mice.
    Journal of Applied Toxicology, 2019
    Co-Authors: Juan Carlos Rodríguez-escamilla, Estefany I. Medina-reyes, Carolina Rodríguez-ibarra, Alejandro Déciga-alcaraz, José O. Flores-flores, Adriana Ganem-rondero, Miriam Rodriguez-sosa, Norma L. Delgado-buenrostro, Luis Ignacio Terrazas, Yolanda I Chirino
    Abstract:

    Food-grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to Bloodstream, which could disturb Barriers such as the Blood-Testis Barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and Blood-Testis Barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on Testis structure, inflammation infiltrate and Blood-Testis Barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the Blood-Testis Barrier were similar in Testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on Testis when E171 is consumed in a liquid matrix.

Yan C Cheng - One of the best experts on this subject based on the ideXlab platform.

  • mtorc1 rps6 regulates Blood Testis Barrier dynamics and spermatogenetic function in the Testis in vivo
    American Journal of Physiology-endocrinology and Metabolism, 2018
    Co-Authors: Tito T. Jesus, Haiqi Chen, Xiang Xiao, Ming Yan, Will M. Lee, Yan C Cheng
    Abstract:

    The Blood-Testis Barrier (BTB), conferred by Sertoli cells in the mammalian Testis, is an important ultrastructure that supports spermatogenesis. Studies using animal models have shown that a disru...

  • regulation of Blood Testis Barrier assembly in vivo by germ cells
    The FASEB Journal, 2017
    Co-Authors: Yan Zhang, Alia Batool, Ji-xin Tang, Shou-long Deng, Xiu-xia Wang, Yu-qian Wang, Cheng Jin, Tie-cheng Sun, Suren Chen, Yan C Cheng
    Abstract:

    The assembly of the Blood-Testis Barrier (BTB) during postnatal development is crucial to support meiosis. However, the role of germ cells in BTB assembly remains unclear. Herein, KitW/KitWV mice were used as a study model. These mice were infertile, failing to establish a functional BTB to support meiosis due to c-Kit mutation. Transplantation of undifferentiated spermatogonia derived from normal mice into the Testis of KitW/KitWV mice triggered functional BTB assembly, displaying cyclic remodeling during the epithelial cycle. Also, transplanted germ cells were capable of inducing Leydig cell testosterone production, which could enhance the expression of integral membrane protein claudin 3 in Sertoli cells. Early spermatocytes were shown to play a vital role in directing BTB assembly by expressing claudin 3, which likely created a transient adhesion structure to mediate BTB and cytoskeleton assembly in adjacent Sertoli cells. In summary, the positive modulation of germ cells on somatic cell function provides useful information regarding somatic-germ cell interactions.-Li, X.-Y., Zhang, Y., Wang, X.-X., Jin, C., Wang, Y.-Q., Sun, T.-C., Li, J., Tang, J.-X., Batool, A., Deng, S.-L., Chen, S.-R., Cheng, C. Y., Liu, Y.-X. Regulation of Blood-Testis Barrier assembly in vivo by germ cells.

  • actin binding proteins in Blood Testis Barrier function
    Current Opinion in Endocrinology Diabetes and Obesity, 2015
    Co-Authors: Dolores D. Mruk, Yan C Cheng
    Abstract:

    Purpose of review This review examines the role of actin binding proteins (ABPs) on Blood-Testis Barrier (BTB), an androgen-dependent ultrastructure in the Testis, in particular their involvement on BTB remodeling during spermatogenesis.

  • crosstalk between desmoglein 2 desmocollin 2 src kinase and coxsackie and adenovirus receptor zo 1 protein complexes regulates Blood Testis Barrier dynamics
    The International Journal of Biochemistry & Cell Biology, 2010
    Co-Authors: Pearl P Y Lie, Yan C Cheng, Dolores D. Mruk
    Abstract:

    Morphological studies in the Testis reported the presence of 'desmosome-like' junctions between Sertoli cells at the Blood-Testis Barrier, whose function is also constituted by tight junctions and basal ectoplasmic specializations. Unfortunately, little is known about the role of desmosomes in Blood-Testis Barrier dynamics. This study aims to fill this gap with the functional investigation of two desmosomal cadherins, desmoglein-2 and desmocollin-2, by their specific knockdown in Sertoli cells cultured in vitro. Reminiscent of the Blood-Testis Barrier in vivo, desmosome-like structures were visible by electron microscopy when Sertoli cells were cultured at high density, thereby forming a polarized epithelium with functional cell junctions. At this point, we opted to focus our efforts on desmoglein-2 and desmocollin-2 based on results which illustrated desmosomal mRNAs to be expressed by Sertoli and germ cells, as well as on results which illustrated desmoglein-2 to co-immunoprecipitate with plakoglobin, c-Src and desmocollin-2. Simultaneous knockdown of desmoglein-2 and desmocollin-2 not only led to a reduction in and mislocalization of zonula occludens-1, but also perturbed the localization of c-Src and coxsackie and adenovirus receptor at the cell-cell interface, resulting in disruption of tight junction permeability Barrier. We hereby propose a novel regulatory protein complex composed of desmoglein-2, desmocollin-2, c-Src, coxsackie and adenovirus receptor and zonula occludens-1 at the Blood-Testis Barrier.