Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule

M. Adam, S. Saller, S. Ströbl, Jon Hennebold, Gregory Dissen, Sergio Ojeda, Richard Stouffer, D. Berg, U. Berg, A. Mayerhofer

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Study Question Is decorin (DCN), a putative modulator of growth factor (GF) signaling, expressed in the primate ovary and does it play a role in ovarian biology? Summary Answer DCN expression in the theca, the corpus luteum (CL), its presence in the follicular fluid (FF) and its actions revealed in human IVF-derived granulosa cells (GCs), suggest that it plays multiple roles in the ovary including folliculogenesis, ovulation and survival of the CL. What is Known Already DCN is a secreted proteoglycan, which has a structural role in the extracellular matrix (ECM) and also interferes with the signaling of multiple GF/GF receptors (GFRs). However, DCN expression and action in the primate ovary has yet to be determined. Study Design, Size, Duration Archival human and monkey ovarian samples were analyzed. Studies were conducted using FF and GC samples collected from IVF patients. Participants/Materials, Setting , Methods Immunohistochemistry, western blotting, RT-PCR, quantitative RT-PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) studies were complemented by cellular studies, including the measurements of intracellular Ca2, reactive oxygen species (ROS), epidermal GF receptor (EGFR) phosphorylation by DCN and caspase activity. Main Results and The Role of ChanceImmunohistochemistry revealed strong DCN staining in the connective tissue and follicular thecal compartments, but not in GCs of pre-antral and antral follicles. Pre-ovulatory follicles could not be studied, but DCN was associated with connective tissue of CL samples and the cytoplasm of luteal cells. DCN expression in monkey CL doubled (P <0.05) towards the end of the luteal lifespan. DCN was found in human FF obtained from IVF patients (mean: 12.9 ng/ml; n 20) as determined by ELISA. DCN mRNA and/or protein were detected in freshly isolated and cultured, luteinized human GCs. In the latter, exogenous human recombinant DCN increased intracellular Ca2 levels and induced the production of ROS in a concentration-dependent manner. DCN, like epidermal GF, phosphorylated EGFR significantly (P <0.05) and reduced the activity of caspase 3/7 in cultured GCs. The data indicate the expression of DCN in the theca of growing follicles, in FF of ovulatory follicles and in the CL. Therefore, DCN may exert paracrine actions via GF/GFR systems in multiple ovarian compartments. Limitations, Reasons for Caution Functional studies were performed in cultures of human luteinized GCs, which are an apt model but may not fully mirror the pre-ovulatory GC compartment or the CL. Other human ovarian cells, including the thecal cells, were not available. Wider Implications of The Findings In accordance with its evolving roles in other organs, ovarian DCN is an ECM-associated component, which acts as a multifunctional regulator of GF signaling in the primate ovary. DCN may thus be involved in folliculogenesis, ovulation and the regulation of the CL survival in primates. Study Funding/Competing Interest (S)This study was supported by Deutsche Forschungsgemeinschaft (DFG) MA1080/17-3 and in part DFG MA1080/21-1 (to AM), NIH grants HD24870 (S.R.O. and R.L.S.), the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement HD18185 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (S.R.O.) and 8P51OD011092-53 for the operation of the Oregon National Primate Research Center (G.A.D., J.D.H., S.R.O. and R.L.S).

    Original languageEnglish (US)
    Pages (from-to)3249-3258
    Number of pages10
    JournalHuman Reproduction
    Volume27
    Issue number11
    DOIs
    StatePublished - Nov 2012

    Fingerprint

    Decorin
    Primates
    Extracellular Matrix
    Corpus Luteum
    Granulosa Cells
    Follicular Fluid
    Ovary
    Intercellular Signaling Peptides and Proteins
    Growth Factor Receptors
    Ovulation
    Connective Tissue
    Haplorhini
    Reactive Oxygen Species
    Enzyme-Linked Immunosorbent Assay
    National Institute of Child Health and Human Development (U.S.)
    Caspase 7
    Luteal Cells
    Polymerase Chain Reaction
    Organized Financing

    Keywords

    • apoptosis
    • corpus luteum
    • epidermal growth factor receptor
    • follicle
    • reactive oxygen species

    ASJC Scopus subject areas

    • Rehabilitation
    • Obstetrics and Gynecology
    • Reproductive Medicine

    Cite this

    Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule. / Adam, M.; Saller, S.; Ströbl, S.; Hennebold, Jon; Dissen, Gregory; Ojeda, Sergio; Stouffer, Richard; Berg, D.; Berg, U.; Mayerhofer, A.

    In: Human Reproduction, Vol. 27, No. 11, 11.2012, p. 3249-3258.

    Research output: Contribution to journalArticle

    Adam, M. ; Saller, S. ; Ströbl, S. ; Hennebold, Jon ; Dissen, Gregory ; Ojeda, Sergio ; Stouffer, Richard ; Berg, D. ; Berg, U. ; Mayerhofer, A. / Decorin is a part of the ovarian extracellular matrix in primates and may act as a signaling molecule. In: Human Reproduction. 2012 ; Vol. 27, No. 11. pp. 3249-3258.
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    abstract = "Study Question Is decorin (DCN), a putative modulator of growth factor (GF) signaling, expressed in the primate ovary and does it play a role in ovarian biology? Summary Answer DCN expression in the theca, the corpus luteum (CL), its presence in the follicular fluid (FF) and its actions revealed in human IVF-derived granulosa cells (GCs), suggest that it plays multiple roles in the ovary including folliculogenesis, ovulation and survival of the CL. What is Known Already DCN is a secreted proteoglycan, which has a structural role in the extracellular matrix (ECM) and also interferes with the signaling of multiple GF/GF receptors (GFRs). However, DCN expression and action in the primate ovary has yet to be determined. Study Design, Size, Duration Archival human and monkey ovarian samples were analyzed. Studies were conducted using FF and GC samples collected from IVF patients. Participants/Materials, Setting , Methods Immunohistochemistry, western blotting, RT-PCR, quantitative RT-PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) studies were complemented by cellular studies, including the measurements of intracellular Ca2, reactive oxygen species (ROS), epidermal GF receptor (EGFR) phosphorylation by DCN and caspase activity. Main Results and The Role of ChanceImmunohistochemistry revealed strong DCN staining in the connective tissue and follicular thecal compartments, but not in GCs of pre-antral and antral follicles. Pre-ovulatory follicles could not be studied, but DCN was associated with connective tissue of CL samples and the cytoplasm of luteal cells. DCN expression in monkey CL doubled (P <0.05) towards the end of the luteal lifespan. DCN was found in human FF obtained from IVF patients (mean: 12.9 ng/ml; n 20) as determined by ELISA. DCN mRNA and/or protein were detected in freshly isolated and cultured, luteinized human GCs. In the latter, exogenous human recombinant DCN increased intracellular Ca2 levels and induced the production of ROS in a concentration-dependent manner. DCN, like epidermal GF, phosphorylated EGFR significantly (P <0.05) and reduced the activity of caspase 3/7 in cultured GCs. The data indicate the expression of DCN in the theca of growing follicles, in FF of ovulatory follicles and in the CL. Therefore, DCN may exert paracrine actions via GF/GFR systems in multiple ovarian compartments. Limitations, Reasons for Caution Functional studies were performed in cultures of human luteinized GCs, which are an apt model but may not fully mirror the pre-ovulatory GC compartment or the CL. Other human ovarian cells, including the thecal cells, were not available. Wider Implications of The Findings In accordance with its evolving roles in other organs, ovarian DCN is an ECM-associated component, which acts as a multifunctional regulator of GF signaling in the primate ovary. DCN may thus be involved in folliculogenesis, ovulation and the regulation of the CL survival in primates. Study Funding/Competing Interest (S)This study was supported by Deutsche Forschungsgemeinschaft (DFG) MA1080/17-3 and in part DFG MA1080/21-1 (to AM), NIH grants HD24870 (S.R.O. and R.L.S.), the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement HD18185 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (S.R.O.) and 8P51OD011092-53 for the operation of the Oregon National Primate Research Center (G.A.D., J.D.H., S.R.O. and R.L.S).",
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    AU - Adam, M.

    AU - Saller, S.

    AU - Ströbl, S.

    AU - Hennebold, Jon

    AU - Dissen, Gregory

    AU - Ojeda, Sergio

    AU - Stouffer, Richard

    AU - Berg, D.

    AU - Berg, U.

    AU - Mayerhofer, A.

    PY - 2012/11

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    N2 - Study Question Is decorin (DCN), a putative modulator of growth factor (GF) signaling, expressed in the primate ovary and does it play a role in ovarian biology? Summary Answer DCN expression in the theca, the corpus luteum (CL), its presence in the follicular fluid (FF) and its actions revealed in human IVF-derived granulosa cells (GCs), suggest that it plays multiple roles in the ovary including folliculogenesis, ovulation and survival of the CL. What is Known Already DCN is a secreted proteoglycan, which has a structural role in the extracellular matrix (ECM) and also interferes with the signaling of multiple GF/GF receptors (GFRs). However, DCN expression and action in the primate ovary has yet to be determined. Study Design, Size, Duration Archival human and monkey ovarian samples were analyzed. Studies were conducted using FF and GC samples collected from IVF patients. Participants/Materials, Setting , Methods Immunohistochemistry, western blotting, RT-PCR, quantitative RT-PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) studies were complemented by cellular studies, including the measurements of intracellular Ca2, reactive oxygen species (ROS), epidermal GF receptor (EGFR) phosphorylation by DCN and caspase activity. Main Results and The Role of ChanceImmunohistochemistry revealed strong DCN staining in the connective tissue and follicular thecal compartments, but not in GCs of pre-antral and antral follicles. Pre-ovulatory follicles could not be studied, but DCN was associated with connective tissue of CL samples and the cytoplasm of luteal cells. DCN expression in monkey CL doubled (P <0.05) towards the end of the luteal lifespan. DCN was found in human FF obtained from IVF patients (mean: 12.9 ng/ml; n 20) as determined by ELISA. DCN mRNA and/or protein were detected in freshly isolated and cultured, luteinized human GCs. In the latter, exogenous human recombinant DCN increased intracellular Ca2 levels and induced the production of ROS in a concentration-dependent manner. DCN, like epidermal GF, phosphorylated EGFR significantly (P <0.05) and reduced the activity of caspase 3/7 in cultured GCs. The data indicate the expression of DCN in the theca of growing follicles, in FF of ovulatory follicles and in the CL. Therefore, DCN may exert paracrine actions via GF/GFR systems in multiple ovarian compartments. Limitations, Reasons for Caution Functional studies were performed in cultures of human luteinized GCs, which are an apt model but may not fully mirror the pre-ovulatory GC compartment or the CL. Other human ovarian cells, including the thecal cells, were not available. Wider Implications of The Findings In accordance with its evolving roles in other organs, ovarian DCN is an ECM-associated component, which acts as a multifunctional regulator of GF signaling in the primate ovary. DCN may thus be involved in folliculogenesis, ovulation and the regulation of the CL survival in primates. Study Funding/Competing Interest (S)This study was supported by Deutsche Forschungsgemeinschaft (DFG) MA1080/17-3 and in part DFG MA1080/21-1 (to AM), NIH grants HD24870 (S.R.O. and R.L.S.), the Eunice Kennedy Shriver NICHD/NIH through cooperative agreement HD18185 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (S.R.O.) and 8P51OD011092-53 for the operation of the Oregon National Primate Research Center (G.A.D., J.D.H., S.R.O. and R.L.S).

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    KW - corpus luteum

    KW - epidermal growth factor receptor

    KW - follicle

    KW - reactive oxygen species

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