C Yan Cheng

..These summaries are helpful to investigators in the field who seek to understand the molecular mechanism of action of AF-2364 in the rat testis and to explore its possible use for male contraception...

..These findings provide a new window of research for investigators in the field to tackle the functional regulation of spermatogenesis...

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..This local regulatory axis is the emerging target for male contraception...

..In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive...

..Herein, we provide a critical review based on the latest findings in the field regarding the regulation of these cellular events. These recent findings also open up a new window for investigators studying blood-tissue barriers...

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..Furthermore, these recent findings have unraveled some unexpected molecules to be targeted for male contraceptive development, which are also targets of toxicant-induced male reproductive dysfunction...

..An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives...

..Collectively, these findings illustrate multiple potential targets are present at the BTB for innovative contraceptive development and for better delivery of drugs to alleviate toxicant-induced reproductive dysfunction in men...

..We discuss herein the mechanisms that maintain the cross-talk between ES and blood-testis barrier to facilitate cell movement and orientation in the seminiferous epithelium...

..Lastly, we describe a working model, which can be used to design future functional experiments to explore the involvement of FAK in BTB dynamics by investigators in the field...

..Yet an agent that selectively disrupts AJs (e.g., AF-2364) can limit its effects exclusively at the Sertoli-germ cell adhesive site without perturbing the Sertoli-Sertoli TJs...

..In summary, these results illustrate that Sertoli-germ cell anchoring junction dynamics in the testis are regulated, at least in part, via the beta1-integrin/PI3K/PKB/ERK signaling pathway...

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..In addition to its role in conferring cell adhesion formation, the p-FAK/c-Src protein complex apparently also regulates apical ES disruption via the ERK signaling pathway...

..In summary, these results illustrate that the cadherin/catenin is a crucial cell adhesion complex that regulates AJ dynamics in the testis, and its functionality is likely modulated by the MTMR2/c-Src protein complex...

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..Thus, this may permit the occludin/ZO-1 complexes to maintain the BTB integrity when the cadherin/catenin complexes are dissociated to facilitate germ cell movement...

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..These findings indicate that P-glycoprotein is involved in BTB restructuring during spermatogenesis but that P-glycoprotein-mediated restructuring does not "open up" the BTB to make it freely permeable to drugs...

..In summary, the use of an FSH mutant-occludin peptide conjugate is a feasible nanodevice to transiently compromise the BTB...

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..These results illustrate that the interactions among IQGAP1, Cdc42, and beta-catenin are crucial to the regulation of Sertoli-germ cell, but not Sertoli-Sertoli cell, AJ dynamics in the seminiferous epithelium...

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..In short, the data reported herein have shown that c-Src, Csk, and CK2 are novel protein kinases in AJ dynamics in the testis...

..In summary, Fer kinase structurally associates with the N-cadherin/catenin protein complex in the testis and can possibly be used to mediate signaling function via the cadherin/catenin protein complex...

..14-3-3theta may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis...

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..These results illustrate that BTB dynamics in vivo are regulated by the TGF-beta3/p38 MAP kinase pathway, which in turn determines the level of occludin at the site of Sertoli cells TJs...

..However, TGF-beta3 selectively disrupts Sertoli-germ cell adhesion in the seminiferous epithelium to facilitate germ cell migration without compromising BTB when TbetaRI interacts only with adaptor CD2AP...

..In summary, Cdc42 is a crucial regulatory component in the TGF-beta3-mediated cascade of events that leads to the disruption of the TJ fibrils above the preleptotene spermatocytes to facilitate their transit...

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..These results illustrate that the CDH2/CATNB-mediated adhesion function in the testis is regulated, at least in part, via the NOS/cGMP/PRKG/CATNB pathway...

..g., apical ES) in the testis. The biology and regulation based on recent studies in the testis are of interest to cell biologists in the field, in particular their regulation, which perhaps is applicable to tumorigenesis...

..In summary, bisphenol A reversibly perturbs the integrity of the blood-testis barrier in Sertoli cells in vitro, which can also serve as a suitable model for studying the dynamics of the blood-testis 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...

..Furthermore, FAK was shown to be a molecular target of cadmium because its knockdown would desensitize Sertoli cells to cadmium-induced TJ barrier disruption. In summary, FAK is a unique regulator of BTB dynamics in the testis...

..In summary, c-Yes regulates BTB and apical ES integrity by maintaining proper distribution of integral membrane proteins and actin filament organization at these sites...

..Collectively, these results suggest that SMS2 may play a crucial role in the lipid metabolism in acrosome formation and the plasma membrane restructuring from late round spermatids to early elongating spermatids...

..These results thus unequivocally demonstrate that the cadherin/catenin complex, which can be up-regulated by testosterone, is indeed present between Sertoli and germ cells and is used for the assembly of functional AJs...

..In summary, this report illustrates that Sertoli germ cell AJ dynamics are regulated, at least in part, via the integrin/ROCK/LIMK/cofilin signaling pathway...

..Other factors such as proteases, protease inhibitors, GTPases, kinases, and phosphatases also come into play. In this review, we focus on this cellular phenomenon, recapping recent developments in the field...

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..g., occludin, claudin-11 and JAM-A) was noted when testis lysates from Adjudin-treated rats were used for co-immunoprecipitation experiments, suggesting that P-gp may enhance BTB function during Sertoli-germ cell junction restructuring...

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..In summary, this report demonstrates for the first time that BTB dynamics are regulated by TGF-beta3 and TNFalpha via an enhancement of protein endocytosis at the BTB...

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..It is possible that the receptor utilized by viral pathogens to breakthrough the epithelial barrier was also employed by developing germ cells to migrate through the inter-Sertoli cell junctions...

..Herein, we discuss a novel approach with the aim of developing a nonhormonal male contraceptive for future human use, one that involves perturbing adhesion between Sertoli and germ cells in the testis...

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..Thus, this mechanism is used by the testis to facilitate AJ restructuring to accommodate germ cell migration while maintaining the BTB integrity...

..Collectively, these results illustrate that while these adaptors are structurally associated with the cadherin/catenin complex in the testis, they are regulated differently...

..The potential to specifically target the ES may also mean that contraceptive action could be achieved without perturbing the hypothalamic-pituitary-testicular axis...

..This review summarizes recent advances of studies on TGF-betas in the testis, highlighting their regulatory role in TJ dynamics...

..The net result of this interaction likely regulates germ cell movement in the seminiferous epithelium...

..Collectively, these results illustrate NOS is an important physiological regulator of TJ dynamics in the testis, exerting its effects via the NO/soluble guanylate cyclase/cGMP/protein kinase G signaling pathway...

..Neither compound affected the hypothalamus-pituitary-testicular axis, and both compounds were neither hepatotoxic nor nephrotoxic. These results suggest that these two compounds are safe for further development...

..Possible regulators that mediate cytokine-induced junction restructuring, including gap junction and extracellular matrix, and the role of testosterone on junction dynamics in the testis will also be discussed...

..These results thus unequivocally demonstrate that TGFbeta3 utilizes the p38 MAP kinase pathway to regulate Sertoli cell TJ dynamics...

..In summary, CNP secreted by Sertoli and germ cells into the BTB microenvironment regulates BTB dynamics during spermatogenesis...

..In summary, Cx43 is crucial for TJ reassembly at the BTB during its cyclic restructuring throughout the seminiferous epithelial cycle of spermatogenesis...

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..Thus, these findings demonstrate that FAK is an integrated regulatory component of the occludin-ZO-1 protein complex, suggesting that functional studies can be performed to study the role of FAK in BTB dynamics...

..More important, a transient disruption of the blood-testis barrier was also detected...

..In this way, MAPKs would synchronize cell cycle progression in primary spermatocytes with junction remodeling and cell migration across the BTB...

..Herein, we provide a critical review based on the recently available data regarding the cross-talk between TJ and anchoring junction to allow simultaneous maintenance of the BTB and germ cell movement across the seminiferous epithelium...

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..It is possible that localized production of IL1A by Sertoli and/or germ cells in vivo results in BTB restructuring, and this may facilitate the movement of leptotene spermatocytes across the BTB...

..Modulation of efflux pump function via specific inhibitors could help to deliver contraceptives to the testis in the future...

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..These results, taken collectively, suggest SOD(EX) is an important antioxidant molecule in the testis that is under germ cell regulation...

..Here, we discuss recent findings relating to these two junction types in the testis, highlighting prospective areas that should be investigated in future studies...

..Collectively these results demonstrate that adjudin targets the apical ES as well as the basal ES and tight junction, which in turn delays assembly of the BTB...

..Besides, we highlight important areas of research that can now be undertaken, and functional studies that can be designed to tackle different issues pertinent to junction restructuring during spermatogenesis...

..In this article, we highlight the latest developments regarding contraceptive delivery to men and with the aim of providing useful information for investigators in future studies...

..Furthermore, a molecular model is presented regarding how cytokines selectively regulate TJ/AJ restructuring in the epithelium during spermatogenesis...

..While it will still take much time and effort of intensive investigation before a product can reach the consumable market, these findings have provided hope for better family planning involving men...

..This approach will not only provide a better understanding of ES dynamics, but also will yield innovative approaches for the development of male contraceptives...

..As important, an increase in the kinetics of occludin internalization but a decrease in its rate of degradation was noted following IL-1? treatment. These results indicate that IL-1? is a critical regulator of BTB dynamics...

..It also highlights specific areas for future research toward understanding the precise physiological relationship between junction dynamics and spermatogenesis...

..An integrated model of how these three MAPKs regulate adhesion function in the seminiferous epithelium is also presented. This model will serve as the framework for future investigation in the field...

..Taken collectively, these observations strengthen the notion that ECM is involved in the regulation of junction dynamics in addition to its structural role in the testis...

..5 microg Adjudin per kg b.w. was administered intraperitoneally, which was similar to results when 50 mg per kg b.w. was given orally. This represents a substantial increase in Adjudin's selectivity and efficacy as a male contraceptive...

..Specific research areas that are open for further investigation are also highlighted...

..This paper reviews some recent findings on Rho GTPases in the field with emphasis on the studies in the testis, upon which future studies can be designed to delineate the role of Rho GTPases in spermatogenesis...

..The inhibitory effect on GATA-1 gene expression was specific to testicular cells and was not observed in erythroid cells...

..Knowledge on viral invasion and leukocyte transmigration has also shed insights into germ cell movement during spermatogenesis...

..g., ES) and TJ. In addition, several in vivo models that can be used to delineate the function of adaptors in the testis are described, and the role of adaptors in regulating junction dynamics pertinent to spermatogenesis is discussed...

..The net result of these interactions, in turn, determines the steady-state protein levels at the Sertoli-Sertoli cell interface at the BTB...

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..Specifically, we use the adult rat or mouse testis as a model to highlight the significance of transcriptional and translational regulation. Specific areas of research that require further attentions are also highlighted...

..This finding illustrates for the first time that a cell-matrix restructuring event occurs in normal cell physiology at the cell-cell interface in the testis, highlighting the significance of alpha(2)-MG in the regulation of BTB function...

..This review critically discusses these latest findings in the field in light of their significance in the biology and regulation of the BTB pertinent to spermatogenesis...

..It also offers new insight into: (i) developing novel approaches for male contraception, and (ii) the causes of unexplained male infertility. ..

..In summary, these studies not only will define the regulation of AJ dynamics, they will identify new leads and innovative approaches for male contraceptive development. ..

..Second and perhaps most importantly, the disrupted BTB can be "resealed", making this model uniquely suitable to study the biology and regulation of BTB re-assembly during spermatogenesis. ..

..It also offers new insight into: (i) developing novel approaches for male contraception, and (ii) the causes of unexplained male infertility. ..

..It also offers new insight into: (i) developing novel approaches for male contraception, and (ii) the causes of unexplained male infertility. ..