Changes in blood vessel stability and its regulation in the corpus luteum during pregnancy in rats

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The present study investigates changes in blood vessel stability and its regulation in the corpus luteum (CL) during pregnancy in rats. First, blood vessel stability in the CL was evaluated on days 3, 7. 9, 12, 15 and 21 of pregnancy based on the vascular leakage, which was quantified by Evans blue assay. Vascular leakage was highest on day 3, thereafter decreased until day 15 and increased on day 21 again, suggesting that blood vessels in the CL are not stabilized on day 3 yet, stabilized during mid-pregnancy, and destabilized on day 21 of pregnancy. Secondly, to study the regulation of blood vessel stability, expression of angiopoietins was examined in the CL during pregnancy. Immunohistochemical study showed both angiopoietin-1 (Ang-1) and Ang-2 expressions in luteal cells. Ang-1 mRNA and protein levels were significantly higher on days 12 and 15 than those on days 3 and 21, whereas there was no significant change in Ang-2 expression. Since estradiol stimulates angiogenesis and contributes to CL development during mid-pregnancy, we finally studied whether estradiol regulates blood vessel stability and angiopoietin expression. Rats undergoing hypophysectomy-hysterectomy (Hypox-Hect) on day 12 were treated with estradiol until day 15. Vascular leakage was increased and Ang-1 expression was decreased by Hypox-Hect, and these effects were completely reversed by estradiol treatment. In conclusion, blood vessel stability in the CL is likely to be associated with CL development and CL regression, and may be regulated by angiopoietins. Estradiol contributes to blood vessel stabilization via Ang-1 in the CL during mid-pregnancy.