Expression of VEGF and its receptors in the bovine endometrium throughout the estrous cycle: effects of VEGF on prostaglandin production in endometrial cells.

Vascular endothelial growth factor (VEGF) is a well known angiogenic factor that has been suggested to play some physiological roles in reproductive organs. To clarify whether VEGF is involved in regulating bovine endometrial function locally, in experiment 1, we determined the expression of VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 throughout the estrous cycle in endometrial tissues. Endometrial tissue was collected at estrus (Day 0), the early I (Days 2-3), early II (Days 5-6), mid (Days 8-12) and late luteal stages (Days 15-17) and the follicular stage (Days 19-21). RT-PCR and Western blotting analysis revealed that VEGF mRNA expression at estrus was higher than at the early I, early II and late luteal stages (P<0.05), whereas VEGF protein content was greatest at the early I luteal stage and decreased thereafter. VEGFR1 mRNA expression was lower at estrus and at the early I and early II luteal stages than at the other stages, whereas VEGFR1 protein expression did not change significantly throughout the estrous cycle (P<0.05). VEGFR2 mRNA expression was higher at the mid and late luteal stages than at the early I and early II luteal stages, and VEGFR2 protein was higher at the mid and late luteal stages than at estrus (P<0.05). In experiment 2, to determine the effect of VEGF on prostaglandin (PG) F2alpha and PGE2 production by endometrial cells, cultured endometrial epithelial and stromal cells were exposed to VEGF (0, 5, 50, 100 and 200 ng/ml) for 24 h. VEGF (200 ng/ml) stimulated PGF2alpha production by stromal cells (P<0.05), but not PGE2 production. VEGF did not affect PG production by endometrial epithelial cells. The overall results suggest that VEGF and its receptors are regulated throughout the estrous cycle and that VEGF participates in the local regulation of bovine endometrial function by a selective modulation of PGF2alpha production in stromal cells in an auto- and/or paracrine manner.