{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:57Z","timestamp":1784557257410,"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":[[2020,5]]},"abstract":"<jats:p>\n                    Polycystic ovary syndrome (PCOS), one of the most common female endocrine disorder, is a prevalent cause of infertility. Hyperandrogenism is a key feature in PCOS and is correlated with increased expression of VEGF and cytokines in the ovaries. We have previously shown that pigment epithelium-derived factor (PEDF), an endogenous protein, presents potent anti-angiogenic and anti-inflammatory activities in the ovary and negates the effects of cytokines and VEGF. Additionally, PEDF plays a role in both pathophysiology and treatment of ovarian-hyperstimulation syndrome (OHSS), frequently seen in PCOS patients. We established hyperandrogenic-PCOS models, both\n                    <jats:italic>in vivo<\/jats:italic>\n                    , using mice exposed prenatally to dihydrotestosterone (DHT) and,\n                    <jats:italic>in vitro<\/jats:italic>\n                    , using human primary granulosa cells (hpGCs) and human granulosa cell line (KGN). In PCOS-induced mice, the mRNA levels of\n                    <jats:italic>I<\/jats:italic>\n                    <jats:italic>l-6<\/jats:italic>\n                    ,\n                    <jats:italic>V<\/jats:italic>\n                    <jats:italic>egf<\/jats:italic>\n                    and\n                    <jats:italic>Amh<\/jats:italic>\n                    were higher than those of control; yet, treatment with rPEDF decreased these levels. Moreover, treating OHSS-induced PCOS-mice with rPEDF alleviated all OHSS symptoms. Stimulation of hpGCs with DHT resulted in downregulation of PEDF mRNA expression, concomitantly with a significant increase in\n                    <jats:italic>IL-6<\/jats:italic>\n                    and\n                    <jats:italic>IL-8<\/jats:italic>\n                    mRNAs expression. However, co-stimulation of DHT with rPEDF attenuated the increase in cytokines expression. The anti-inflammatory effect of PEDF was found to be mediated via PPAR\u03b3 pathway. Our findings suggest that rPEDF treatment may normalize the ovarian angiogenic-inflammatory imbalance, induced by PCOS-associated hyperandrogenism. Moreover, the therapeutic potency of PEDF in preventing OHSS symptomes offers a rationale for using PEDF as novel physiological treatment for PCOS sequels.\n                  <\/jats:p>","DOI":"10.1530\/joe-19-0603","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T19:06:21Z","timestamp":1584126381000},"page":"291-300","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":9,"title":["Pigment epithelium-derived factor (PEDF) negates hyperandrogenic PCOS features"],"prefix":"10.1530","volume":"245","author":[{"given":"Irit","family":"Miller","sequence":"first","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadas","family":"Bar-Joseph","sequence":"additional","affiliation":[{"name":"2The TMCR Unit, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba","family":"Nemerovsky","sequence":"additional","affiliation":[{"name":"1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Tel-Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ido","family":"Ben-Ami","sequence":"additional","affiliation":[{"name":"3IVF and Infertility Unit, Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, The 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, Ramat-Aviv, 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\/245\/2\/JOE-19-0603.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/245\/2\/JOE-19-0603.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:06Z","timestamp":1784555826000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/245\/2\/291-300\/5257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/joe-19-0603","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5]]}}}