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Pregnancy Ameliorates the Inhibitory Effects of 2-Methoxyestradiol on Angiogenesis in Primary Sheep Uterine Endothelial Cells

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Wisconsin, WI, Madison, USA

    Sana M. Salih MD, MMS, Arvinder Kapur PhD, Samet Albayrak MD & Ronald R. Magness

  2. Department of Obstetrics and Gynecology, Baylor College of Medicine, 600 Highland Avenue, Clinical Science Center, H4/625, 53791, TX, Houston, USA

    Salama A. Salama PhD

Authors
  1. Sana M. Salih MD, MMS
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  2. Arvinder Kapur PhD
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  3. Samet Albayrak MD
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  4. Salama A. Salama PhD
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  5. Ronald R. Magness
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Correspondence to Sana M. Salih MD, MMS.

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Salih, S.M., Kapur, A., Albayrak, S. et al. Pregnancy Ameliorates the Inhibitory Effects of 2-Methoxyestradiol on Angiogenesis in Primary Sheep Uterine Endothelial Cells. Reprod. Sci. 18, 858–867 (2011). https://doi.org/10.1177/1933719111398149

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