Ginkgo biloba extract 761 reduces vascular permeability of the ovary and improves the symptom of ovarian hyperstimulation syndrome in a rat model

Abstract BackgroundGinkgo biloba extract (EGb) has been widely applied in the treatment of cerebrovascular and neurological diseases. However, the effect of EGb761 on ovarian hyperstimulation syndrome (OHSS), a vascular disorder and life-threatening complication of In vitro fertilization and Intracytoplasmic sperm injection therapy (IVF/ICSI), has not been evaluated. MethodsForty female Wistar rats aged 22-days old (D22) were divided into eight groups: Control rats received intraperitoneal injection of saline for 5 consecutive days (D22-D26); OHSS-model group received 10 IU equine chorionic gonadotropin (eCG) for 4 consecutive days (D22-D25) and 30 IU of human chorionic gonadotropin (hCG) on the 5th day (D26); Prophylactic treatment group received three doses of EGb761 (50mg/kg/d, 100mg/kg/d, 200mg/kg/d) one hour before injection of eCG (hCG) for 7 consecutive days; Therapeutic treatment group received three doses of EGb761 (50mg/kg/d, 100mg/kg/d, 200mg/kg/d) 48 hours after injection of eCG (hCG) for 7 consecutive days. ResultsWe found the therapeutic treatment group exhibited the lowest ovarian and renal mass index, vascular permeability, estradiol and progesterone concentrations, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) protein expression. ConclusionsEGb761 decreases vascular permeability in OHSS rat model by inhibiting VEGF and VEGFR expression, which may contribute to the prevention and treatment of OHSS. Furthermore, therapeutic medication is superior to prophylactic medication.

This chapter outlines ovarian hyperstimulation syndrome (OHSS), the most serious complication of ovulation induction. OHSS is characterized by massive cystic enlargement of the ovaries, an increase in vascular permeability, and a shift of fluid to the extravascular compartments (mainly the peritoneal cavity), with the formation of ascites. The management and prevention of OHSS is described in this chapter.

Abstract Although advances in the prediction and management of ovarian hyperstimulation syndrome (OHSS) have been introduced, complete prevention is not yet possible. Previously, we and other authors have shown that vascular endothelial growth factor, angiopoietins (ANGPTs) and sphingosine-1-phosphate are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of platelet-derived growth factor (PDGF) ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-β and ANGPT2 remain unchanged. In the present work, we investigated the role of PDGF-B in OHSS by evaluating ligand protein levels in follicular fluid (FF) from women at risk of developing OHSS and by using an immature rat model of OHSS. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients (P < 0.05). In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight (P < 0.05), reduced serum progesterone (P < 0.05) and lowered the percentage of cysts (P < 0.05), compared to untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea (CL). PDGF-B treatment also restored the expression of steroidogenic acute regulatory protein (P < 0.05) and P450 cholesterol side-chain cleavage enzyme (P < 0.01) to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures, and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B increased the levels of junction proteins claudin-5 (P < 0.05), occludin (P < 0.05) and β-catenin (P < 0.05), while boosting the extracellular deposition of collagen IV surrounding the ovarian vasculature (PP < 0.01), compared to OHSS alone. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, which may lead to the development of novel prediction markers and therapeutic strategies.