Regulation and action of angiogenic factors in the primate ovary.
The ephemerality of the maturing follicle and subsequent corpus luteum as they perform their gametogenic and/or endocrine functions during the ovarian cycle is associated with remarkable changes in local vasculature. Studies on the angiogenic and angiolytic process in the ovary, rare in healthy adult tissues, complement recent efforts to understand vasculogenesis in embryonic tissues and to control angiogenesis in pathologic states such as cancer. Several reports indicate that the newly discovered vascular-specific angiogenic factors are expressed in the ovary, notably members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families plus their receptors (VEGF-Rs, neuropilins, Tie). Unlike in many other tissues, gonadotropic hormones (particularly luteinizing hormone, [LH]) are major stimulators of angiogenesis and VEGF/Ang expression in the ovary. However, local factors such as insulin-like growth factors or oxygen tension likely modulate the angiogenic processes. Recent studies employing systemic or local administration of anti-angiogenic drugs (TNP-470 or fumagillin) or specific VEGF antagonists (VEGF antibody or soluble VEGFR-1) demonstrate a vital role for normal angiogenesis and VEGF action in follicle development, ovulation, or corpus luteum function. Further studies discerning the various angiogenic factors and their roles in controlling the growth, maturation, function, and regression of the vasculature in ovarian compartments during the menstrual cycle could yield novel strategies for manipulating fertility or for alleviating infertility.
Stouffer
R L
RL
Division of Reproductive Sciences, Oregon Regional Primate Research Center/Oregon Health Sciences University, Beaverton, OR 97006, USA. stouffri@ohsu.edu
Martínez-Chequer
J C
JC
Molskness
T A
TA
Xu
F
F
Hazzard
T M
TM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000502:physiology; D003338:Corpus Luteum / Q000098:blood supply / Q000502:physiology; D003510:Cyclohexanes; D016228:Endothelial Growth Factors / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006133:Growth Substances / Q000502:physiology*; D007986:Luteinizing Hormone / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D006080:Ovarian Follicle / Q000098:blood supply / Q000502:physiology; D010053:Ovary / Q000098:blood supply* / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D010060:Ovulation / Q000502:physiology; D010100:Oxygen / Q000502:physiology; D011323:Primates / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D012259:Ribonuclease, Pancreatic / Q000502:physiology; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D006063:Chorionic Gonadotropin; D003510:Cyclohexanes; D016228:Endothelial Growth Factors; D005231:Fatty Acids, Unsaturated; D012739:Gonadal Steroid Hormones; D006133:Growth Substances; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D012717:Sesquiterpenes; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C105154:angiogenin receptor; C026211:fumagillin; D007986:Luteinizing Hormone; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D010100:Oxygen; D000077609:O-(Chloroacetylcarbamoyl)fumagillol