{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:54Z","timestamp":1784557254858,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:p>\n                    PCOS is the most common endocrinopathy in women; associated with obesity and insulin resistance (IR). IR leads to accumulation of advanced-glycation-end-products (AGEs) and their receptor, RAGE. PCOS patients have increased levels of vascular endothelial growth factor (VEGF), interleukin 6\/8 (IL-6\/8) and anti-M\u03cbllerian-hormone (AMH). PEDF is a secreted-glycoprotein known for its anti-angiogenic and anti-inflammatory properties. We aimed to elucidate the role of PEDF in the pathogenesis and treatment of PCOS. We used a prenatal PCOS mouse model and fed the female offspring a high-fat diet, inducing metabolic PCOS (met.PCOS) characteristics. Female offspring were divided into three groups: control; met.PCOS; met.PCOS\u2009+\u2009recombinant PEDF (rPEDF). Met.PCOS mice gained more weight, had elevated serum IL-6 and higher mRNA levels of AMH, PEDF and RAGE in their granulosa cells (GCs) than met.PCOS\u2009+\u2009rPEDF mice. An\n                    <jats:italic>in vitro<\/jats:italic>\n                    Met.PCOS model in human GCs (KGN) line was induced by prolonged incubation with insulin\/AGEs, causing development of IR. Under the same conditions, we observed an elevation of VEGF, IL-6\/8 mRNAs, concomitantly with an increase in PEDF mRNA, intracellular protein levels, and an elevation of PEDF receptors (PEDF-Rs) mRNA and protein. Simultaneously, a reduction in the secretion of PEDF from GCs, was measured in the medium. The addition of rPEDF (5 nM) activated P38 signaling, implying that PEDF-Rs maintained functionality, and negated AGE-induced elevation of IL-6\/8 and VEGF mRNAs. Decreased PEDF secretion may be a major contributor to hyperangiogenesis and chronic inflammation, which lie at the core of PCOS pathogenesis. rPEDF treatment may restore physiological angiogenesis inflammatory balance, thus suggesting a potential therapeutic role in PCOS.\n                  <\/jats:p>","DOI":"10.1530\/joe-19-0297","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T14:50:00Z","timestamp":1572360600000},"page":"297-308","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":13,"title":["Elucidating the role of pigment epithelium-derived factor (PEDF) in metabolic PCOS models"],"prefix":"10.1530","volume":"244","author":[{"given":"Michal","family":"Silber","sequence":"first","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"2Department of OB\/GYN, Meir Medical Center, Kfar Saba, Israel"},{"name":"3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Miller","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Bar-Joseph","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Ben-Ami","sequence":"additional","affiliation":[{"name":"4IVF and Fertility Unit, Department of OB\/GYN, Shaare Zedek Medical Center, Jerusalem, Israel"},{"name":"5The Hebrew University Medical School of Jerusalem, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Shalgi","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/244\/2\/JOE-19-0297.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/244\/2\/JOE-19-0297.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:54Z","timestamp":1784555814000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/244\/2\/297-308\/5238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-19-0297","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]}}}