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  1. Article ; Online: Brinster Spermatogonial Stem Cell Transplantation 25

    Dobrinski, Ina / Orwig, Kyle

    The International journal of developmental biology

    2020  Volume 63, Issue 11-12, Page(s) 573–578

    Abstract: The Symposium, co-sponsored by the Institute of Regenerative Medicine, the University Research Foundation, the Center for Research on Reproduction and Women's Health, the Penn Center for the Study of Epigenetics in Reproduction, and Penn Vet at the ... ...

    Abstract The Symposium, co-sponsored by the Institute of Regenerative Medicine, the University Research Foundation, the Center for Research on Reproduction and Women's Health, the Penn Center for the Study of Epigenetics in Reproduction, and Penn Vet at the University of Pennsylvania, commemorated the 25
    MeSH term(s) Animals ; Anniversaries and Special Events ; Humans ; Infertility, Male/therapy ; Male ; Mice ; Spermatogenesis ; Spermatogonia/transplantation ; Stem Cell Transplantation/methods
    Language English
    Publishing date 2020-02-14
    Publishing country Spain
    Document type Congress
    ZDB-ID 1036070-0
    ISSN 1696-3547 ; 0214-6282
    ISSN (online) 1696-3547
    ISSN 0214-6282
    DOI 10.1387/ijdb.190362id
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Role for Exchange of Extracellular Vesicles in Porcine Spermatogonial Co-Culture.

    Thiageswaran, Shiama / Steele, Heather / Voigt, Anna Laura / Dobrinski, Ina

    International journal of molecular sciences

    2022  Volume 23, Issue 9

    Abstract: Spermatogonial stem cells (SSCs) provide the basis for lifelong male fertility through self-renewal and differentiation. Prepubertal male cancer patients may be rendered infertile by gonadotoxic chemotherapy and, unlike sexually mature men, cannot store ... ...

    Abstract Spermatogonial stem cells (SSCs) provide the basis for lifelong male fertility through self-renewal and differentiation. Prepubertal male cancer patients may be rendered infertile by gonadotoxic chemotherapy and, unlike sexually mature men, cannot store sperm. Alternatively, testicular biopsies taken prior to treatment may be used to restore fertility in adulthood. Testicular SSC populations are limited, and in vitro culture systems are required to increase numbers of SSCs for treatment, demanding culture systems for SSC propagation. Using the pig as a non-rodent model, we developed culture systems to expand spermatogonia from immature testis tissue, comparing different feeders (Sertoli cells, peritubular myoid cells (PMCs) and pig fetal fibroblasts (PFFs)). Spermatogonia co-cultured with Sertoli cells, PMCs and PFFs had comparable rates of proliferation and apoptosis. To elucidate the mechanism behind the beneficial nature of feeder layers, we investigated the role of extracellular vesicles in crosstalk between spermatogonia and feeder cells. Sertoli cell-released exosomes are incorporated by spermatogonia, and inhibition of exosomal release reduces spermatogonial proliferation. Together, these results show that PMCs, PFFs and Sertoli cells promote spermatogonial proliferation in co-culture, with exosomal exchange representing one possible mechanism. Further characterization of exosomal cargo may ultimately allow the development of feeder-free culture systems for clinical use.
    MeSH term(s) Adult ; Animals ; Cells, Cultured ; Coculture Techniques ; Extracellular Vesicles ; Humans ; Male ; Sertoli Cells ; Spermatogonia ; Swine ; Testis
    Language English
    Publishing date 2022-04-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23094535
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Regulation of Cell Types Within Testicular Organoids.

    Lara, Nathalia de Lima E Martins / Sakib, Sadman / Dobrinski, Ina

    Endocrinology

    2021  Volume 162, Issue 4

    Abstract: Organoids are 3-dimensional (3D) structures grown in vitro that emulate the cytoarchitecture and functions of true organs. Therefore, testicular organoids arise as an important model for research on male reproductive biology. These organoids can be ... ...

    Abstract Organoids are 3-dimensional (3D) structures grown in vitro that emulate the cytoarchitecture and functions of true organs. Therefore, testicular organoids arise as an important model for research on male reproductive biology. These organoids can be generated from different sources of testicular cells, but most studies to date have used immature primary cells for this purpose. The complexity of the mammalian testicular cytoarchitecture and regulation poses a challenge for working with testicular organoids, because, ideally, these 3D models should mimic the organization observed in vivo. In this review, we explore the characteristics of the most important cell types present in the testicular organoid models reported to date and discuss how different factors influence the regulation of these cells inside the organoids and their outcomes. Factors such as the developmental or maturational stage of the Sertoli cells, for example, influence organoid generation and structure, which affect the use of these 3D models for research. Spermatogonial stem cells have been a focus recently, especially in regard to male fertility preservation. The regulation of the spermatogonial stem cell niche inside testicular organoids is discussed in the present review, as this research area may be positively affected by recent progress in organoid generation and tissue engineering. Therefore, the testicular organoid approach is a very promising model for male reproductive biology research, but more studies and improvements are necessary to achieve its full potential.
    MeSH term(s) Animals ; Cell Differentiation ; Humans ; Male ; Organoids/cytology ; Organoids/growth & development ; Sertoli Cells/cytology ; Spermatogonia/cytology ; Testis/cytology ; Testis/growth & development
    Language English
    Publishing date 2021-02-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqab033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Comparing the adult and pre-pubertal testis: Metabolic transitions and the change in the spermatogonial stem cell metabolic microenvironment.

    Voigt, Anna Laura / de Lima E Martins Lara, Nathalia / Dobrinski, Ina

    Andrology

    2023  Volume 11, Issue 6, Page(s) 1132–1146

    Abstract: Background: Survivors of childhood cancer often suffer from infertility. While sperm cryopreservation is not feasible before puberty, the patient's own spermatogonial stem cells could serve as a germ cell reservoir, enabling these patients to father ... ...

    Abstract Background: Survivors of childhood cancer often suffer from infertility. While sperm cryopreservation is not feasible before puberty, the patient's own spermatogonial stem cells could serve as a germ cell reservoir, enabling these patients to father their own children in adulthood through the isolation, in vitro expansion, and subsequent transplantation of spermatogonial stem cells. However, this approach requires large numbers of stem cells, and methods for successfully propagating spermatogonial stem cells in the laboratory are yet to be established for higher mammals and humans. The improvement of spermatogonial stem cell culture requires deeper understanding of their metabolic requirements and the mechanisms that regulate metabolic homeostasis.
    Aim: This review gives a summary on our knowledge of spermatogonial stem cell metabolism during maintenance and differentiation and highlights the potential influence of Sertoli cell and stem cell niche maturation on spermatogonial stem cell metabolic requirements during development.
    Results and conclusions: Fetal human spermatogonial stem cell precursors, or gonocytes, migrate into the seminiferous cords and supposedly mature to adult stem cells within the first year of human development. However, the spermatogonial stem cell niche does not fully differentiate until puberty, when Sertoli cells dramatically rearrange the architecture and microenvironment within the seminiferous epithelium. Consequently, pre-pubertal and adult spermatogonial stem cells experience two distinct niche environments potentially affecting spermatogonial stem cell metabolism and maturation. Indeed, the metabolic requirements of mouse primordial germ cells and pig gonocytes are distinct from their adult counterparts, and novel single-cell RNA sequencing analysis of human and porcine spermatogonial stem cells during development confirms this metabolic transition. Knowledge of the metabolic requirements and their changes and regulation during spermatogonial stem cell maturation is necessary to implement laboratory-based techniques and enable clinical use of spermatogonial stem cells. Based on the advancement in our understanding of germline metabolism circuits and maturation events of niche cells within the testis, we propose a new definition of spermatogonial stem cell maturation and its amendment in the light of metabolic change.
    MeSH term(s) Child ; Humans ; Male ; Adult ; Animals ; Swine ; Mice ; Testis/metabolism ; Stem Cell Niche ; Spermatogenesis/physiology ; Semen ; Spermatogonia/metabolism ; Stem Cells/metabolism ; Mammals
    Language English
    Publishing date 2023-02-03
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2696108-8
    ISSN 2047-2927 ; 2047-2919
    ISSN (online) 2047-2927
    ISSN 2047-2919
    DOI 10.1111/andr.13397
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Thesis: Endogene Opioide beim Rind im peripartalen und perinatalen Zeitraum

    Dobrinski, Ina

    1989  

    Size 123 S. : graph. Darst.
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Hannover, Tierärztl. Hochsch., Diss., 1989
    HBZ-ID HT003642937
    Database Catalogue ZB MED Nutrition, Environment, Agriculture

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  6. Article: Organotypic Rat Testicular Organoids for the Study of Testicular Maturation and Toxicology.

    Sakib, Sadman / Lara, Nathalia de Lima E Martins / Huynh, Brandon Christopher / Dobrinski, Ina

    Frontiers in endocrinology

    2022  Volume 13, Page(s) 892342

    Abstract: ... ...

    Abstract An
    MeSH term(s) Animals ; Cell Differentiation ; Male ; Organoids ; Rats ; Spermatogonia/metabolism ; Testis/metabolism
    Language English
    Publishing date 2022-06-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.892342
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Exposure to phthalate esters induces an autophagic response in male germ cells.

    Valenzuela-Leon, Paula / Dobrinski, Ina

    Environmental epigenetics

    2017  Volume 3, Issue 3, Page(s) dvx010

    Abstract: Phthalate esters are plasticizers that impart flexibility to polvinylchloride plastics. As they are not covalently bound, they can leach from a wide range of products, including food containers, medical devices, clothing, and toys, leading to widespread ... ...

    Abstract Phthalate esters are plasticizers that impart flexibility to polvinylchloride plastics. As they are not covalently bound, they can leach from a wide range of products, including food containers, medical devices, clothing, and toys, leading to widespread environmental exposure. Phthalate toxicity has been linked to male infertility by disrupting testosterone production and testis development. Phthalates also impair proliferation and viability of spermatogonial stem cells (SSC), the role of which is to support lifelong spermatogenesis. To elucidate cellular mechanisms in spermatogonia affected by long-term phthalate exposure, we grafted primate testis tissue into mice. Grafts treated with di-
    Language English
    Publishing date 2017-08-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 2831217-X
    ISSN 2058-5888
    ISSN 2058-5888
    DOI 10.1093/eep/dvx010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Three-dimensional testicular organoids as novel

    Sakib, Sadman / Voigt, Anna / Goldsmith, Taylor / Dobrinski, Ina

    Environmental epigenetics

    2019  Volume 5, Issue 3, Page(s) dvz011

    Abstract: Organoids are three dimensional structures consisting of multiple cell types that recapitulate the cellular architecture and functionality of native organs. Over the last decade, the advent of organoid research has opened up many avenues for basic and ... ...

    Abstract Organoids are three dimensional structures consisting of multiple cell types that recapitulate the cellular architecture and functionality of native organs. Over the last decade, the advent of organoid research has opened up many avenues for basic and translational studies. Following suit of other disciplines, research groups working in the field of male reproductive biology have started establishing and characterizing testicular organoids. The three-dimensional architectural and functional similarities of organoids to their tissue of origin facilitate study of complex cell interactions, tissue development and establishment of representative, scalable models for drug and toxicity screening. In this review, we discuss the current state of testicular organoid research, their advantages over conventional monolayer culture and their potential applications in the field of reproductive biology and toxicology.
    Language English
    Publishing date 2019-07-31
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2831217-X
    ISSN 2058-5888 ; 2058-5888
    ISSN (online) 2058-5888
    ISSN 2058-5888
    DOI 10.1093/eep/dvz011
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: De novo morphogenesis of functional testis tissue after ectopic transplantation of isolated cells.

    Dobrinski, Ina

    Organogenesis

    2009  Volume 3, Issue 2, Page(s) 79–82

    Abstract: Development of the mammalian testis begins with sex specific differentiation of the bipotential gonad during fetal development, continues after birth with proliferation and differentiation of testicular somatic cells, and culminates at puberty with germ ... ...

    Abstract Development of the mammalian testis begins with sex specific differentiation of the bipotential gonad during fetal development, continues after birth with proliferation and differentiation of testicular somatic cells, and culminates at puberty with germ cell differentiation, meiotic divisions and production of sperm that continues throughout the adult life of the male. Recently, it was demonstrated that functional testicular tissue formed de novo when cells isolated from neonatal porcine or rodent testes were grafted ectopically to mouse hosts. The spermatogenic and interstitial compartments of the testis were regenerated form transplanted cells in a cell autonomous fashion and supported the production of functional haploid germ cells. This fascinating ability of testis cells to recreate the necessary structural and cellular associations to support tissue maturation and germ cell differentiation can now be harnessed to study aspects of mammalian spermatogenesis and testicular morphogenesis in an accessible in vivo system.
    Language English
    Publishing date 2009-03-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2159583-5
    ISSN 1555-8592 ; 1547-6278
    ISSN (online) 1555-8592
    ISSN 1547-6278
    DOI 10.4161/org.3.2.4944
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro.

    Voigt, Anna Laura / Thiageswaran, Shiama / de Lima E Martins Lara, Nathalia / Dobrinski, Ina

    International journal of molecular sciences

    2021  Volume 22, Issue 4

    Abstract: The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding ... ...

    Abstract The spermatogonial stem cell (SSC) is a unique adult stem cell that requires tight physiological regulation during development and adulthood. As the foundation of spermatogenesis, SSCs are a potential tool for the treatment of infertility. Understanding the factors that are necessary for lifelong maintenance of a SSC pool in vivo is essential for successful in vitro expansion and safe downstream clinical usage. This review focused on the current knowledge of prepubertal testicular development and germ cell metabolism in different species, and implications for translational medicine. The significance of metabolism for cell biology, stem cell integrity, and fate decisions is discussed in general and in the context of SSC in vivo maintenance, differentiation, and in vitro expansion.
    MeSH term(s) Adult ; Adult Germline Stem Cells/cytology ; Adult Germline Stem Cells/physiology ; Animals ; Cell Culture Techniques/methods ; Cell Differentiation/physiology ; Cells, Cultured ; Humans ; Male ; Spermatogenesis/physiology ; Spermatogonia/cytology ; Spermatogonia/physiology
    Language English
    Publishing date 2021-02-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22041998
    Database MEDical Literature Analysis and Retrieval System OnLINE

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