Targeting angiogenesis in the pathological ovary

2013 ◽  
Vol 25 (2) ◽  
pp. 362 ◽  
Author(s):  
W. Colin Duncan ◽  
Junko Nio-Kobayashi
Keyword(s):  
Ovarian Hyperstimulation Syndrome ◽  
Therapeutic Potential ◽  
Polycystic Ovary ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Theoretical Possibility ◽  
Clinical Role ◽  
And Function ◽  
Endothelial Growth Factor

The ovary is a key tissue in the study of physiological neo-vascularisation in the adult and its study has highlighted important molecules involved in the regulation of angiogenesis in vivo. These include vascular endothelial growth factor, delta-like ligand 4, thrombospondin-1, prokineticin-1 and prostaglandin E2. Targeting these molecular pathways has therapeutic potential and their manipulation has an increasing preclinical and clinical role in the management of the pathological ovary. Targeting angiogenic pathways has utility in the promotion of ovarian angiogenesis to improve tissue and follicle survival and function as well as the prevention and management of ovarian hyperstimulation syndrome. There is a theoretical possibility that targeting angiogenesis may improve the function of the polycystic ovary and a real role for targeting angiogenesis in ovarian cancer.

scholarly journals Lysophosphatidic Acid Up-Regulates Expression of Interleukin-8 and -6 in Granulosa-Lutein Cells through Its Receptors and Nuclear Factor-κB Dependent Pathways: Implications for Angiogenesis of Corpus Luteum and Ovarian Hyperstimulation Syndrome

2008 ◽  
Vol 93 (3) ◽  
pp. 935-943 ◽  
Author(s):  
Shee-Uan Chen ◽  
Chia-Hung Chou ◽  
Hsinyu Lee ◽  
Chi-Hong Ho ◽  
Chung-Wu Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Lysophosphatidic Acid ◽  
Ovarian Hyperstimulation Syndrome ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Ovarian Hyperstimulation ◽  
Vascular Endothelial ◽  
Nuclear Factor ◽  
Lpa Receptors ◽  
Endothelial Growth Factor

Abstract Context: Lysophosphatidic acid (LPA) was found at significant amounts in follicular fluid of preovulatory follicle. The lysophospholipase D activity of serum from women receiving ovarian stimulation was higher than women with natural cycles. Angiogenic cytokines, including IL-6, IL-8, and vascular endothelial growth factor, increased in plasma and ascites of patients with ovarian hyperstimulation syndrome. The role of LPA in ovarian follicles is unclear. Objective: Our objective was to investigate the expression of LPA receptors and function of LPA in granulosa-lutein cells. Design: Granulosa-lutein cells were obtained from women undergoing in vitro fertilization. We examined the expression of LPA receptors using RT-PCR. The effects of LPA on the expression of IL-6, IL-8, and vascular endothelial growth factor were examined. Signal pathways of LPA were delineated. The functions of secretory angiogenic factors were tested using human umbilical vein endothelial cells. Results: The LPA1, LPA2, and LPA3 receptors’ mRNA was identified in granulosa-lutein cells. LPA enhanced IL-8 and IL-6 expressions in a dose- and time-dependent manner. LPA functioned via LPA receptors, Gi protein, MAPK/ERK, p38, phosphatidylinositol 3-kinase/Akt, and nuclear factor-κB, and transactivation of epidermal growth factor receptor. LPA induced IL-8 and IL-6 through different pathways. LPA-induced IL-8 and IL-6 increased permeability of human umbilical vein endothelial cell monolayer. Conclusions: LPA induces IL-8 and IL-6 expressions through LPA receptors and nuclear factor-κB dependent pathways in granulosa-lutein cells. The LPA in preovulatory follicles may play a role in the angiogenesis of corpus luteum. Large amounts of LPA-induced IL-8 and IL-6 from multiple corpora luteae of stimulated ovaries may be one of the pathophysiological causes of ovarian hyperstimulation syndrome.

Sign in / Sign up

Export Citation Format

Share Document