Stimulatory effects of eicosanoids on ovarian angiogenesis in early luteal phase in cyclooxygenase-2 inhibitor-treated rats

Our previous study demonstrated that impaired ovarian vasculature is responsible for the decrease in serum progesterone observed in cyclooxygenase (COX)-2 inhibitor-treated rats. To explore the role of arachidonic acid metabolites in the formation of the corpus luteum, we determined in the present study the effects of prostaglandin (PG) and thromboxane (TX) receptor agonists together with vascular endothelial growth factor (VEGF) on progesterone secretion and angiogenesis in the newly formed corpus luteum in NS-398 (a selective inhibitor of COX-2)-treated rats. Uterine injection of PGE2 or U-46619 (TXA2 receptor agonist) prevented decreased levels of serum progesterone and ovarian hemoglobin, an indicator of amounts of vasculature in NS-398-treated rats. Luteal capillary vessel establishment was inhibited by NS-398, as determined by histological examination of ovarian vascular plexuses, while administration of PGE2 reversed the effect. VEGF enhanced the levels of serum progesterone and ovarian hemoglobin, and increased the density of ovarian capillaries. However, VEGF-induced angiogenesis was inhibited by NS-398 treatment. These results suggest that PGE2 and TXA2 stimulate angiogenesis in the newly formed corpus luteum and that there is a possibility that these eicosanoids are involved in VEGF-induced progesterone production and the increase in luteal blood flow.