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 17ß-estradiol (17ßE2), or 10(-9) to 10(-6) mol/L 2-ME2. Angiogenesis, apotosis, and cell morphology were assessed by capillary tube formation, flowcytometry, and immunohistochemistry. 17ßE2 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 17ßE2 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.