title: Pregnancy ameliorates the inhibitory effects of 2-methoxyestradiol on angiogenesis in primary sheep uterine endothelial cells.
abstract: The estrogen metabolite 2-methoxyestradiol (2-ME2) is one of the most potent antiangiogenic and proapoptotic endogenous steroids. Herein, we investigate the effects of 2-ME2 on angiogenesis of cultured primary ovine uterine artery endothelial cells (UAECs) from nonpregnant follicular (F-UAECs), nonpregnant luteal (L-UAECs), and pregnant ewes (P-UAECs). Uterine artery endothelial cells were treated with vehicle control, 10(-8) mol/L 17β-estradiol (17βE2), or 10(-9) to 10(-6) mol/L 2-ME2. Angiogenesis, apotosis, and cell morphology were assessed by capillary tube formation, flowcytometry, and immunohistochemistry. 17βE2 stimulated while 10(-6) mol/L 2-ME2 inhibited capillary tube formation in F-UAECs (P < .05). The inhibitory effects of 2-ME2 on angiogenesis were minimal in L-UAECs and were absent in P-UAECs when compared to controls. 10(-6) mol/L 2-ME2 increased apoptosis and inhibited microtubular structure equally in pregnant and nonpregnant UAECs when compared to control or 17βE2 treatments. Thus, 2-ME2 inhibit capillary tube formation in F-UAECs while L-UAECs and P-UAECs are relatively unresponsive to the inhibitory effects of 2ME2 indicating that the pregnancy phenotypic state of the UAECs may modulate the action of 2-ME2 on capillary angiogenesis.
authors.affiliation: Department of Obstetrics and Gynecology, University of Wisconsin, 600 Highland Avenue, Madison, WI 53791, USA. salih@wisc.edu
authors.forename: Sana M
authors.initials: SM
authors.lastname: Salih
authors.forename: Arvinder
authors.initials: A
authors.lastname: Kapur
authors.forename: Samet
authors.initials: S
authors.lastname: Albayrak
authors.forename: Salama A
authors.initials: SA
authors.lastname: Salama
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Magness
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D008858:Microscopy, Phase-Contrast; D008870:Microtubules / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012756:Sheep; D055988:Uterine Artery / Q000187:drug effects*; D014599:Uterus / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects*
chemical_list: D004958:Estradiol; D000077584:2-Methoxyestradiol