{
    "abstract": "There is currently no cure for infertility in women with a poor ovarian response (POR). Neogenin is reported to be abundantly expressed in the ovary; however, its role in mammalian follicular development is unclear and its ligand and signaling pathway remain uncertain. We systematically investigated the role of neogenin and the ligand repulsive guidance molecule c (RGMc) during follicular development. We treated hyperstimulated mouse ovaries with RGMc and analyzed follicular development. Furthermore, we investigated clusters of up/downregulated genes in RGMc-treated ovaries using whole-transcriptome next-generation sequencing (NGS). In addition, we investigated whether expression of up/downregulated factors identified by NGS was also altered in cumulus cells (CCs) of patients with a POR. The number of oocytes was 40% higher in RGMc-treated ovaries than in control ovaries. NGS data indicated that prostaglandin D2 (PGD2) was involved in the RGMc signaling pathway during follicular development. RGMc treatment significantly elevated the PGD2 level in culture medium of CCs obtained from patients with a POR. Our results demonstrate that RGMc as neogenin ligand promotes follicular development in ovaries via the PGD2 signaling pathway. Therefore, it may be possible to use RGMc for ovarian stimulation in patients with a POR.",
    "authors": [
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.",
            "firstname": "Yu Jin",
            "initials": "YJ",
            "lastname": "Kim"
        },
        {
            "affiliation": "Department of Biomedical Science, CHA University, Gyeonggi-do, Seongnam 13488, Korea.",
            "firstname": "YoungJoon",
            "initials": "Y",
            "lastname": "Park"
        },
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.",
            "firstname": "Yeo Reum",
            "initials": "YR",
            "lastname": "Park"
        },
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.",
            "firstname": "Young Sang",
            "initials": "YS",
            "lastname": "Kim"
        },
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.",
            "firstname": "Hye Ran",
            "initials": "HR",
            "lastname": "Lee"
        },
        {
            "affiliation": "Institute of Animal Genetic Resources Affiliated with Traditional Hanwoo Co., Ltd., Boryeong 33402, Korea.",
            "firstname": "Sang Jin",
            "initials": "SJ",
            "lastname": "Lee"
        },
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.",
            "firstname": "Myung Joo",
            "initials": "MJ",
            "lastname": "Kim"
        },
        {
            "affiliation": "Department of Biomedical Science, CHA University, Gyeonggi-do, Seongnam 13488, Korea.",
            "firstname": "KyuBum",
            "initials": "K",
            "lastname": "Kwack"
        },
        {
            "affiliation": "Department of Biomedical Science, CHA University, Gyeonggi-do, Seongnam 13488, Korea.",
            "firstname": "Jung Jae",
            "initials": "JJ",
            "lastname": "Ko"
        },
        {
            "affiliation": "CHA Fertility Center Seoul Station, Seoul 04637, Korea.\nDepartment of Biomedical Science, CHA University, Gyeonggi-do, Seongnam 13488, Korea.",
            "firstname": "Jae Ho",
            "initials": "JH",
            "lastname": "Lee"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.3390/biomedicines9030280\n10.1111/j.1471-0528.1997.tb11020.x\n10.1093/humupd/dmw001\n10.1093/humrep/der092\n10.1097/GCO.0000000000000452\n10.4103/0974-1208.183515\n10.1530/rep.1.01074\n10.3791/53696\n10.1016/j.biocel.2006.10.023\n10.3390/ijms18030491\n10.1186/s41232-017-0037-6\n10.1074/jbc.M110.180919\n10.1242/dev.118638\n10.1016/j.tcb.2016.11.009\n10.1369/jhc.6A7031.2006\n10.1371/journal.pone.0101989\n10.1016/j.bbadis.2012.05.013\n10.7554/eLife.13909\n10.1002/dvdy.21612\n10.1002/mrd.1080250411\n10.1210/endo-120-2-819\n10.1095/biolreprod.114.120931\n10.1016/j.anireprosci.2017.09.008\n10.2741/s140\n10.1371/journal.pone.0096115\n10.1186/1757-2215-4-3\n10.1186/s12958-018-0359-5\n10.1095/biolreprod66.5.1230\n10.1016/j.fertnstert.2006.09.017\n10.1016/j.tjog.2018.06.015\n10.1093/humrep/deg291\n10.1093/molehr/gaq032\n10.1093/humrep/dem336\n10.1093/molehr/gaq031\n10.1016/j.fertnstert.2014.11.015",
    "journal": "Biomedicines",
    "keywords": [
        "PGD2",
        "RGMc",
        "follicular development",
        "neogenin",
        "ovary",
        "poor ovarian response"
    ],
    "methods": null,
    "publication_date": "2021-04-04",
    "pubmed_id": "33801938\n9422028\n26843539\n21505041\n29664789\n27382230\n16885529\n27341639\n17137827\n28245592\n29259705\n21149453\n27143755\n28007423\n16982849\n25013897\n22634430\n27021569\n18629867\n1691651\n2879726\n25078684\n28967452\n21196365\n24763822\n21352547\n29716588\n11967182\n17481622\n30122578\n12832367\n20435608\n17951581\n20435609\n25497448",
    "results": null,
    "title": "Role of RGMc as a Neogenin Ligand in Follicular Development in the Ovary.",
    "xml": "<Element 'PubmedArticle' at 0x788504153bf0>"
}