The Dual Role of PEDF in the Pathogenesis of OHSS: Negating Both Angiogenic and Inflammatory Pathways

Irit Miller; Dana Chuderland; Hadas Grossman; Raphaël Ron-El; Ido Ben‐Ami; Ruth Shalgi

doi:10.1210/jc.2016-1744

The Dual Role of PEDF in the Pathogenesis of OHSS: Negating Both Angiogenic and Inflammatory Pathways

Irit Miller, Dana Chuderland, Hadas Grossman, Raphaël Ron-El, Ido Ben‐Ami, Ruth Shalgi

In: The Journal of Clinical Endocrinology & Metabolism · 2016 · vol. 101(12) , pp. 4699–4709 · doi:10.1210/jc.2016-1744 · PMID:27680872 · W2524310044

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⚙ AI-generated summary by claude@2026-06, 2026-06-14 ⓘ

Pigment epithelium-derived factor (PEDF) mitigates ovarian hyperstimulation syndrome (OHSS) by suppressing both angiogenic and inflammatory pathways, as demonstrated in vitro and in vivo.

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Abstract

CONTEXT: Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproductive technologies. This complex syndrome is known to involve massive angiogenesis and inflammation. We have previously established the anti-angiogenic involvement of pigment epithelium-derived factor (PEDF) in the pathophysiology and treatment of OHSS. OBJECTIVE: Evaluate the anti-inflammatory role of PEDF in OHSS. DESIGN: In vivo mouse OHSS model and in vitro cultures of granulosa cells. MAIN OUTCOME: Changes in the expression of PEDF, IL-6, IL-8, and vascular endothelial growth factor (VEGF) were measured by quantitative PCR and ELISA; OHSS symptoms were recorded (body and ovarian weight gain and peritoneal vascular leakage quantified by the modified Miles's assay). RESULTS: Rat granulosa cell-line stimulated with lysophosphatidic acid (LPA), exhibited a significant increase in IL-6 expression, concomitantly with a decrease in PEDF level (P < .01). Co-stimulation with recombinant PEDF (rPEDF) decreased the expression of IL-6 significantly (P < .05). Furthermore, the expression of IL-6 and IL-8 increased in LPA-stimulated human primary granulosa cells (P < .01). Co-stimulation with rPEDF decreased the expression of LPA-induced IL-6 and IL-8 mRNA and protein by 4- and 2- to 5-fold, respectively. IL-8-stimulated human primary granulosa cells exhibited increased expression of VEGF mRNA; co-stimulation with hCG induced a significantly higher increase in the expression of VEGF mRNA (P < .001), which was counteracted by rPEDF. Subcutaneous injection of 0.5 mg/kg rPEDF to OHSS-induced mice reduced the increased expression of IL-6 in the ovary (P < .01) and alleviated the severity of all OHSS parameters. CONCLUSIONS: Our findings provide a framework that correlates down-regulation of OHSS symptoms caused by PEDF with both angiogenic and inflammatory pathways.