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  1. Artikel ; Online: The role of homozygous LOF variant of the PNLDC1 gene in oligo-astheno-teratozoospermia (OAT) and male infertility.

    Cheng, Zi-Xin / Du, Li / He, Zuping

    Asian journal of andrology

    2023  Band 25, Heft 6, Seite(n) 754–755

    Mesh-Begriff(e) Male ; Humans ; Avena ; Infertility, Male/genetics ; Oligospermia/genetics ; Asthenozoospermia ; Spermatozoa
    Sprache Englisch
    Erscheinungsdatum 2023-06-02
    Erscheinungsland China
    Dokumenttyp Letter ; Comment
    ZDB-ID 2075824-8
    ISSN 1745-7262 ; 1008-682X
    ISSN (online) 1745-7262
    ISSN 1008-682X
    DOI 10.4103/aja202322
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: WNT5A regulates the proliferation, apoptosis and stemness of human stem Leydig cells via the β-catenin signaling pathway.

    Liu, Wei / Du, Li / Cui, Yinghong / He, Caimei / He, Zuping

    Cellular and molecular life sciences : CMLS

    2024  Band 81, Heft 1, Seite(n) 93

    Abstract: Stem Leydig cells (SLCs) are essential for maintaining normal spermatogenesis as the significant component of testis microenvironment and gonadal aging. Although progress has been achieved in the regulation of male germ cells in mammals and humans, it ... ...

    Abstract Stem Leydig cells (SLCs) are essential for maintaining normal spermatogenesis as the significant component of testis microenvironment and gonadal aging. Although progress has been achieved in the regulation of male germ cells in mammals and humans, it remains unknown about the genes and signaling pathways of human SLCs. Here we have demonstrated, for the first time, that WNT5A (Wnt family member 5a) mediates the proliferation, apoptosis, and stemness of human SLCs, namely NGFR
    Mesh-Begriff(e) Animals ; Humans ; Male ; Leydig Cells/metabolism ; beta Catenin/metabolism ; Testis/metabolism ; Wnt-5a Protein/genetics ; Wnt-5a Protein/metabolism ; Signal Transduction ; Apoptosis ; Cell Proliferation ; Wnt Signaling Pathway/genetics ; Mammals/metabolism
    Chemische Substanzen beta Catenin ; Wnt-5a Protein ; WNT5A protein, human
    Sprache Englisch
    Erscheinungsdatum 2024-02-17
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-023-05077-z
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  3. Artikel ; Online: Zbtb40

    Cui, Yinghong / Zhou, Mingqing / He, Quanyuan / He, Zuping

    Cells

    2023  Band 12, Heft 9

    Abstract: Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the ... ...

    Abstract Studies on the gene regulation of spermatogenesis are of unusual significance for maintaining male reproduction and treating male infertility. Here, we have demonstrated, for the first time, that a loss of ZBTB40 function leads to abnormalities in the morphological and phenotypic characteristics of mouse spermatocytes and spermatids as well as male infertility. We revealed that Zbtb40 was expressed in spermatocytes of mouse testes, and it was co-localized with γH2AX in mouse secondary spermatocytes. Interestingly, spermatocytes of
    Mesh-Begriff(e) Animals ; Humans ; Male ; Mice ; Infertility, Male/genetics ; Mice, Knockout ; Semen ; Spermatocytes ; Spermatozoa ; Testis ; DNA-Binding Proteins/genetics
    Chemische Substanzen Zbtb40 protein, mouse ; DNA-Binding Proteins
    Sprache Englisch
    Erscheinungsdatum 2023-04-26
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12091264
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  4. Artikel ; Online: OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

    Yinghong Cui / Wei Chen / Li Du / Zuping He

    Research, Vol

    2023  Band 6

    Abstract: Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have ... ...

    Abstract Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have demonstrated for the first time that OIP5 (Opa interacting protein 5) controlled the self-renewal and apoptosis of human SSCs. RNA sequencing identified that NCK2 was a target for OIP5 in human SSCs, and interestingly, OIP5 could interact with NCK2 as shown by Co-IP (co-immunoprecipitation), IP-MS (mass spectrometry), and GST pulldown assays. NCK2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their apoptosis. Notably, NCK2 knockdown reversed the influence of OIP5 overexpression on human SSCs. Moreover, OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases, while the levels of numerous cell cycle proteins, including cyclins A2, B1, D1, E1 and H, especially cyclin D1, were remarkably reduced. Significantly, whole-exome sequencing of 777 patients with nonobstructive azoospermia (NOA) revealed 54 single-nucleotide polymorphism mutations of the OIP5 gene (6.95%), while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile men. Collectively, these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with azoospermia. As such, this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA, and it provides new targets for treating male infertility.
    Schlagwörter Science ; Q
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2023-01-01T00:00:00Z
    Verlag American Association for the Advancement of Science
    Dokumenttyp Artikel ; Online
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  5. Artikel ; Online: KLF2 controls proliferation and apoptosis of human spermatogonial stem cells via targeting GJA1.

    Chen, Wei / Cui, Yinghong / Li, Chunyun / He, Caimei / Du, Li / Liu, Wei / He, Zuping

    iScience

    2024  Band 27, Heft 2, Seite(n) 109024

    Abstract: Human spermatogonial stem cells (SSCs) are essential for spermatogenesis and male fertility. However, molecular mechanisms regulating fate determinations of human SSCs remain elusive. In this study, we revealed that KLF2 decreased the proliferation, DNA ... ...

    Abstract Human spermatogonial stem cells (SSCs) are essential for spermatogenesis and male fertility. However, molecular mechanisms regulating fate determinations of human SSCs remain elusive. In this study, we revealed that KLF2 decreased the proliferation, DNA synthesis, and colonization of human SSCs as well as increased apoptosis of these cells. We identified and demonstrated that GJA1 was a target gene for KLF2 in human SSCs. Notably, KLF2 overexpression rescued the reduction of proliferation of human SSCs caused by GJA1 silencing as well as the enhancement of apoptosis of human SSCs. Abnormalities in the higher level of KLF2 and/or
    Sprache Englisch
    Erscheinungsdatum 2024-01-26
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2024.109024
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  6. Artikel ; Online: OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility.

    Cui, Yinghong / Chen, Wei / Du, Li / He, Zuping

    Research (Washington, D.C.)

    2023  Band 6, Seite(n) 162

    Abstract: Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have ... ...

    Abstract Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have demonstrated for the first time that OIP5 (Opa interacting protein 5) controlled the self-renewal and apoptosis of human SSCs. RNA sequencing identified that NCK2 was a target for OIP5 in human SSCs, and interestingly, OIP5 could interact with NCK2 as shown by Co-IP (co-immunoprecipitation), IP-MS (mass spectrometry), and GST pulldown assays. NCK2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their apoptosis. Notably, NCK2 knockdown reversed the influence of OIP5 overexpression on human SSCs. Moreover, OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases, while the levels of numerous cell cycle proteins, including cyclins A2, B1, D1, E1 and H, especially cyclin D1, were remarkably reduced. Significantly, whole-exome sequencing of 777 patients with nonobstructive azoospermia (NOA) revealed 54 single-nucleotide polymorphism mutations of the
    Sprache Englisch
    Erscheinungsdatum 2023-06-07
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2639-5274
    ISSN (online) 2639-5274
    DOI 10.34133/research.0162
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  7. Artikel ; Online: USP11 regulates proliferation and apoptosis of human spermatogonial stem cells via HOXC5-mediated canonical WNT/β-catenin signaling pathway.

    Gao, Jun / Xu, Zhipeng / Song, Weijie / Huang, Jiwei / Liu, Wei / He, Zuping / He, Leye

    Cellular and molecular life sciences : CMLS

    2024  Band 81, Heft 1, Seite(n) 211

    Abstract: Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate ... ...

    Abstract Spermatogonial stem cells (SSCs) are capable of transmitting genetic information to the next generations and they are the initial cells for spermatogenesis. Nevertheless, it remains largely unknown about key genes and signaling pathways that regulate fate determinations of human SSCs and male infertility. In this study, we explored the expression, function, and mechanism of USP11 in controlling the proliferation and apoptosis of human SSCs as well as the association between its abnormality and azoospermia. We found that USP11 was predominantly expressed in human SSCs as shown by database analysis and immunohistochemistry. USP11 silencing led to decreases in proliferation and DNA synthesis and an enhancement in apoptosis of human SSCs. RNA-sequencing identified HOXC5 as a target of USP11 in human SSCs. Double immunofluorescence, Co-immunoprecipitation (Co-IP), and molecular docking demonstrated an interaction between USP11 and HOXC5 in human SSCs. HOXC5 knockdown suppressed the growth of human SSCs and increased apoptosis via the classical WNT/β-catenin pathway. In contrast, HOXC5 overexpression reversed the effect of proliferation and apoptosis induced by USP11 silencing. Significantly, lower levels of USP11 expression were observed in the testicular tissues of patients with spermatogenic disorders. Collectively, these results implicate that USP11 regulates the fate decisions of human SSCs through the HOXC5/WNT/β-catenin pathway. This study thus provides novel insights into understanding molecular mechanisms underlying human spermatogenesis and the etiology of azoospermia and it offers new targets for gene therapy of male infertility.
    Mesh-Begriff(e) Humans ; Male ; Apoptosis/genetics ; Cell Proliferation/genetics ; Wnt Signaling Pathway/genetics ; Homeodomain Proteins/metabolism ; Homeodomain Proteins/genetics ; Azoospermia/metabolism ; Azoospermia/genetics ; Azoospermia/pathology ; Spermatogonia/metabolism ; Spermatogonia/cytology ; Spermatogenesis/genetics ; Adult Germline Stem Cells/metabolism ; beta Catenin/metabolism ; beta Catenin/genetics ; Testis/metabolism ; Testis/cytology ; Thiolester Hydrolases
    Chemische Substanzen Homeodomain Proteins ; USP11 protein, human ; beta Catenin ; Thiolester Hydrolases (EC 3.1.2.-)
    Sprache Englisch
    Erscheinungsdatum 2024-05-09
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-024-05248-6
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: GPx3 knockdown inhibits the proliferation and DNA synthesis and enhances the early apoptosis of human spermatogonial stem cells via mediating CXCL10 and cyclin B1

    Si Wu / Zixin Cheng / Ye Peng / Ying Cao / Zuping He

    Frontiers in Cell and Developmental Biology, Vol

    2023  Band 11

    Abstract: Spermatogenesis is regulated by genetic and epigenetic factors. However, the genes and signaling pathways mediating human spermatogenesis remain largely unknown. Here, we have for the first time explored the expression, function, and mechanism of ... ...

    Abstract Spermatogenesis is regulated by genetic and epigenetic factors. However, the genes and signaling pathways mediating human spermatogenesis remain largely unknown. Here, we have for the first time explored the expression, function, and mechanism of glutathione peroxidase 3 (GPx3) in controlling the proliferation and apoptosis of human spermatogonial stem cells (SSCs). We found that GPx3 was expressed in human SSCs. Notably, we revealed that GPx3 knockdown resulted in the decrease in the proliferation, DNA synthesis, and cyclin B1 level in human SSC lines, which possessed the phenotypic features of human primary SSCs. Flow cytometry and TUNEL assays showed that GPx3 silencing led to enhancement of early apoptosis of human SSC line. RNA sequencing was utilized to identify CXCL10 as a target of GPx3 in human SSCs, and notably, both double immunostaining and co-immunoprecipitation (co-IP) demonstrated that there was an association between GPx3 and CXCL10 in these cells. CXCL10-shRNA resulted in the reduction in the proliferation and DNA synthesis of human SSC line and an increase in apoptosis of these cells. Taken together, these results implicate that GPx3 regulates the proliferation, DNA synthesis, and early apoptosis of human SSC line via mediating CXCL10 and cyclin B1. This study, thus, offers a novel insight into the molecular mechanism regulating the fate determinations of human SSCs and human spermatogenesis.
    Schlagwörter GPx3 ; CXCL10 ; cyclin B1 ; human spermatogonial stem cells ; proliferation ; apoptosis ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-07-01T00:00:00Z
    Verlag Frontiers Media S.A.
    Dokumenttyp Artikel ; Online
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  9. Artikel ; Online: MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility

    Cailin Wan / Wei Chen / Yinghong Cui / Zuping He

    Cells, Vol 11, Iss 3807, p

    2022  Band 3807

    Abstract: Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have ... ...

    Abstract Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have been identified in mice. However, the molecules and signaling pathways underlying human SSCs remain largely unclear. In this study, we have demonstrated that MAP4K4 was predominantly expressed in human UCHL1-positive spermatogonia by double immunocytochemical staining. MAP4K4 knockdown inhibited proliferation of human SSCs and induced their apoptosis. Moreover, MAP4K4 silencing led to inhibition of JNK phosphorylation and MAP4K4 phosphorylation at Ser801. RNA sequencing indicated that MAP4K4 affected the transcription of SPARC , ADAM19 , GPX7 , GNG2 , and COLA1 . Interestingly, the phenotype of inhibiting JNK phosphorylation by SP600125 was similar to MAP4K4 knockdown. Notably, MAP4K4 protein was lower in the testes of patients with non-obstructive azoospermia than those with normal spermatogenesis as shown by Western blots and immunohistochemistry. Considered together, our data implicate that MAP4K4/JNK signaling pathway mediates proliferation and apoptosis of human SSCs, which provides a novel insight into molecular mechanisms governing human spermatogenesis and might offer new targets for gene therapy of male infertility.
    Schlagwörter MAP4K4 ; human spermatogonial stem cells ; JNK ; proliferation ; apoptosis ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2022-11-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility.

    Wan, Cailin / Chen, Wei / Cui, Yinghong / He, Zuping

    Cells

    2022  Band 11, Heft 23

    Abstract: Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have ... ...

    Abstract Spermatogonial stem cells (SSCs) serve as a foundation for spermatogenesis and they are essential for male fertility. The fate of SSC is determined by genetic and epigenetic regulatory networks. Many molecules that regulate SSC fate determinations have been identified in mice. However, the molecules and signaling pathways underlying human SSCs remain largely unclear. In this study, we have demonstrated that MAP4K4 was predominantly expressed in human UCHL1-positive spermatogonia by double immunocytochemical staining. MAP4K4 knockdown inhibited proliferation of human SSCs and induced their apoptosis. Moreover, MAP4K4 silencing led to inhibition of JNK phosphorylation and MAP4K4 phosphorylation at Ser801. RNA sequencing indicated that
    Sprache Englisch
    Erscheinungsdatum 2022-11-28
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11233807
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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