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  1. Article ; Online: The ephrin signaling pathway regulates morphology and adhesion of mouse granulosa cells in vitro.

    Buensuceso, Adrian V / Deroo, Bonnie J

    Biology of reproduction

    2013  Volume 88, Issue 1, Page(s) 25

    Abstract: Follicle-stimulating hormone (FSH)-mediated changes in granulosa cell adhesion and morphology are essential for preovulatory follicle development, given the dramatic changes in follicle size and granulosa cell number that occur during this transition. ... ...

    Abstract Follicle-stimulating hormone (FSH)-mediated changes in granulosa cell adhesion and morphology are essential for preovulatory follicle development, given the dramatic changes in follicle size and granulosa cell number that occur during this transition. Members of the Eph-ephrin family of cell-positioning and adhesion molecules, a family that consists of ephrin ligands and their Ephrin (Eph) receptors, regulate cell location, adhesion, and migration during embryonic development and tumor growth. However, very little is known about ephrin signaling during folliculogenesis. We have found that FSH increases the expression of several members of the Eph-ephrin family and that this signaling regulates granulosa cell morphology and adhesion. FSH induced increased mRNA levels of the ephrin ligand, ephrin-A5 (Efna5), and its receptors, Eph receptors A3, A5, and A8 (Epha3, Epha5, and Epha8, respectively), in granulosa cells. Immunofluorescence studies indicated that EFNA5 and EPHA5 are located in the membrane of granulosa cells of developing mouse follicles. Eph-ephrin signaling directly affected granulosa cell morphology and adhesion. Recombinant EFNA5 reduced cell spreading and increased cell rounding in mouse primary granulosa cells and in a rat granulosa cell line, whereas EPHA5 reduced granulosa cell adhesion in both model systems. Both FSH and forskolin also increased Efna5 and Epha5 mRNA levels in rat and human granulosa cell lines, indicating that FSH regulates these genes via the cAMP-dependent protein kinase A pathway and that this regulation is conserved across different species. The present study identifies Eph-ephrin signaling as a novel FSH-mediated pathway regulating granulosa cell morphology and adhesion.
    MeSH term(s) Animals ; Cell Line ; Ephrins/genetics ; Ephrins/metabolism ; Female ; Follicle Stimulating Hormone/pharmacology ; Gene Expression Regulation/drug effects ; Granulosa Cells/physiology ; Humans ; Mice ; Multigene Family ; Rats ; Receptors, Eph Family/physiology ; Signal Transduction/physiology ; beta Catenin/genetics ; beta Catenin/metabolism
    Chemical Substances Ephrins ; beta Catenin ; Follicle Stimulating Hormone (9002-68-0) ; Receptors, Eph Family (EC 2.7.10.1)
    Language English
    Publishing date 2013-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1118-6
    ISSN 1529-7268 ; 0006-3363
    ISSN (online) 1529-7268
    ISSN 0006-3363
    DOI 10.1095/biolreprod.112.100123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Minireview: Estrogen receptor-beta: mechanistic insights from recent studies.

    Deroo, Bonnie J / Buensuceso, Adrian V

    Molecular endocrinology (Baltimore, Md.)

    2010  Volume 24, Issue 9, Page(s) 1703–1714

    Abstract: The discovery of estrogen receptor-beta (ERbeta) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERbeta action. We now know that ERbeta plays a major role in mediating estrogen action in several tissues and organ ... ...

    Abstract The discovery of estrogen receptor-beta (ERbeta) in 1996 stimulated great interest in the physiological roles and molecular mechanisms of ERbeta action. We now know that ERbeta plays a major role in mediating estrogen action in several tissues and organ systems, including the ovary, cardiovascular system, brain, and the immune system, and that ERbeta and ERalpha generally play distinct physiological roles in the body. Although significant progress has been made toward understanding the molecular mechanisms of ERbeta action, particularly in vitro, there remains a large gap in our understanding of the mechanisms by which ERbeta elicits its biological functions in a true physiological context.
    MeSH term(s) Animals ; Estrogen Receptor beta/metabolism ; Humans ; Ligands ; Receptor Cross-Talk ; Signal Transduction
    Chemical Substances Estrogen Receptor beta ; Ligands
    Language English
    Publishing date 2010-04-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 639167-9
    ISSN 1944-9917 ; 0888-8809
    ISSN (online) 1944-9917
    ISSN 0888-8809
    DOI 10.1210/me.2009-0288
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ephrin-A5 Is Required for Optimal Fertility and a Complete Ovulatory Response to Gonadotropins in the Female Mouse.

    Buensuceso, Adrian V / Son, Alexander I / Zhou, Renping / Paquet, Marilène / Withers, Benjamin M / Deroo, Bonnie J

    Endocrinology

    2016  Volume 157, Issue 2, Page(s) 942–955

    Abstract: Follicle growth and ovulation involve the coordinated expression of many genes, driven by FSH and LH. Reports indicate that Eph receptors and ephrins are expressed in the ovary, suggesting roles in follicle growth and/or ovulation. We previously reported ...

    Abstract Follicle growth and ovulation involve the coordinated expression of many genes, driven by FSH and LH. Reports indicate that Eph receptors and ephrins are expressed in the ovary, suggesting roles in follicle growth and/or ovulation. We previously reported FSH-induced expression of ephrin-A5 (EFNA5) and 4 of its cognate Eph receptors in mouse granulosa cells. We now report that female mice lacking EFNA5 are subfertile, exhibit a compromised response to LH, and display abnormal ovarian histology after superovulation. Efna5(-/-) females litters were 40% smaller than controls, although no difference in litter frequency was detected. The ovarian response to superovulation was also compromised in Efna5(-/-) females, with 37% fewer oocytes ovulated than controls. These results corresponded with a reduction in ovarian mRNA levels of several LH-responsive genes, including Pgr, Ptgs2, Tnfaip6, Ereg, Btc, and Adamts4, suggesting that Efna5(-/-) ovaries exhibit a partially attenuated response to LH. Histopathological analysis indicated that superovulated Efna5(-/-) females exhibited numerous ovarian defects, including intraovarian release of cumulus oocyte complexes, increased incidence of oocytes trapped within luteinized follicles, granulosa cell and follicular fluid emboli, fibrin thrombi, and interstitial hemorrhage. In addition, adult Efna5(-/-) ovaries exhibited a 4-fold increase in multioocyte follicles compared with controls, although no difference was detected in 3-week-old mice, suggesting the possibility of follicle merging. Our observations indicate that loss of EFNA5 in female mice results in subfertility and imply that Eph-ephrin signaling may also play a previously unidentified role in the regulation of fertility in women.
    MeSH term(s) ADAM Proteins/genetics ; ADAM Proteins/metabolism ; ADAMTS4 Protein ; Animals ; Betacellulin/genetics ; Betacellulin/metabolism ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Corpus Luteum/pathology ; Cumulus Cells/pathology ; Cyclooxygenase 2/genetics ; Cyclooxygenase 2/metabolism ; Ephrin-A5/genetics ; Ephrin-A5/metabolism ; Epiregulin/genetics ; Epiregulin/metabolism ; Female ; Fertility/genetics ; Gonadotropins ; Granulosa Cells/pathology ; Infertility/genetics ; Luteinization ; Mice ; Mice, Knockout ; Ovarian Follicle/pathology ; Ovary/metabolism ; Ovary/pathology ; Ovulation/genetics ; Procollagen N-Endopeptidase/genetics ; Procollagen N-Endopeptidase/metabolism ; RNA, Messenger/metabolism ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Superovulation/genetics
    Chemical Substances Betacellulin ; Btc protein, mouse ; Cell Adhesion Molecules ; Ephrin-A5 ; Epiregulin ; Ereg protein, mouse ; Gonadotropins ; RNA, Messenger ; Tnfaip6 protein, mouse ; Ptgs2 protein, mouse (EC 1.14.99.-) ; Cyclooxygenase 2 (EC 1.14.99.1) ; ADAM Proteins (EC 3.4.24.-) ; Procollagen N-Endopeptidase (EC 3.4.24.14) ; ADAMTS4 Protein (EC 3.4.24.82) ; Adamts4 protein, mouse (EC 3.4.24.82)
    Language English
    Publishing date 2016-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/en.2015-1216
    Database MEDical Literature Analysis and Retrieval System OnLINE

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