Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats

The present study was undertaken to investigate the role of vascular endoth elial growth factor (VEGF) in luteal angiogenesis and the regulation of VEG F in the corpus luteum (CL) during mid-pregnancy in rats. Protein concentra tions and mRNA levels of VEGF in the CL significantly increased from Day 9 to Day 12 and remained at the same level as Day 12 until Day 15, To study w hether estradiol is involved in VEGF expression between Day 12 and Day 15, rats undergoing hypophysectomy-hysterectomy on Day 12 were treated with est radiol until Day 15. Protein concentrations and mRNA levels of VEGF in the CL were significantly decreased by hypophysectomy-hysterectomy, and this in hibitory effect was completely reversed by estradiol treatment. Changes in vascular density in the CL were parallel to those in VEGF expression. To ex amine whether the effect of estradiol is mediated by VEGF, anti-VEGF antibo dy was administered to hypophysectomized-hysterectomized rats simultaneousl y with estradiol. The recovery in the vascular density, CL weight, and seru m progesterone concentration caused by estradiol was significantly inhibite d by the anti-VEGF antibody treatment. In conclusion, the present study has demonstrated that VEGF contributes to luteal angiogenesis, CL development, and progesterone production during mid-pregnancy in rats and that luteal V EGF expression is increased by estradiol.