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Angiogenesis in the Human Corpus Luteum: Changes in Expression of Angiopoietins in the Corpus Luteum throughout the Menstrual Cycle and in Early Pregnancy

Division of Obstetrics and Gynecology (N.S., A.S., I.M., H.A., T.T., Y.Y., H.T.), Department of Reproductive, Pediatric, and Infectious Science, Yamaguchi University School of Medicine, Ube 755-8505, Japan; and Department of Pathology (T.S.), Tohoku University School of Medicine, Sendai 980-8575, Japan

Address all correspondence and requests for reprints to: Norihiro Sugino, M.D., Ph.D., Division of Obstetrics and Gynecology, Department of Reproductive, Pediatric and Infectious Science, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan. E-mail: sugino{at}yamaguchi-u.ac.jp.

Context: Blood vessel stabilization is regulated by angiopoietins and important for angiogenesis in the corpus luteum.

Objective: To study angiogenesis and blood vessel stabilization in the human corpus luteum, changes in expression of angiopoietin (Ang)-1, Ang-2, and their specific receptor, Tie-2, together with the number of blood vessels and pericytes were examined in the corpus luteum throughout the menstrual cycle and in early pregnancy.

Design: The number of blood vessels and pericytes was determined by immunohistochemistry for CD34 and -smooth muscle actin, respectively. Ang and Tie-2 expression were examined by immunohistochemistry or RT-PCR.

Results: The number of blood vessels increased during the early luteal phase, whereas the number of pericytes was small in the early luteal phase and increased in the midluteal phase, suggesting that angiogenesis is undergoing during the early luteal phase and blood vessels are stabilized in the midluteal phase. Blood vessels and pericytes decreased in number during the late luteal phase. The increased number of both blood vessels and pericytes seen in the corpus luteum of early pregnancy suggests that angiogenesis is undergoing accompanied by blood vessel stabilization. Ang-2 expression with low Ang-1 expression was found during the early luteal phase. Thereafter, increasing Ang-1 expression during the midluteal phase, declining Ang-1 expression with continued Ang-2 expression during the late luteal phase, and relatively high Ang-1 expression in early pregnancy were observed.

Conclusions: The change in Ang expression is closely associated with angiogenesis, blood vessel stabilization, and blood vessel regression during the divergent phases of luteal formation, luteal regression, and luteal rescue by pregnancy.

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