Time-Course of the Uterine Response to Estradiol-17β in Ovariectomized Ewes: Expression of Angiogenic Factors1

Abstract

Uterine expression of angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) was evaluated in ovariectomized ewes at 0, 2, 4, 8, 24, 48, or 72 h after estradiol (E2) treatment. Endometrial VEGF mRNA increased more than 5-fold from 0 to 4 h, remained elevated at 8 h, and then declined through 72 h after E2 treatment. In contrast, endometrial bFGF mRNA remained constant from 0 to 4 h, increased 2.2-fold from 4 to 8 h, remained elevated at 24 h, and then declined through 72 h. Immunostaining for VEGF was present in myometrial and endometrial microvessels (arterioles, venules, and/or capillaries) and also in myometrial smooth muscle; the pattern of VEGF immunostaining followed that of mRNA expression, being elevated at 4 and 8 h after E2 treatment. Immunostaining for bFGF was present exclusively in uterine glands; the pattern of bFGF immunostaining also followed that of its mRNA, being elevated at 8 and 24 h after E2. On the basis of these observations, we suggest that VEGF and bFGF are probably important factors responsible for the dramatic uterine microvascular response that occurs 8 to 24 h after E2 treatment in ovariectomized ewes.

Differential Effect of Follicle-Stimulating Hormone and Estradiol on Expressions of Vascular Endothelial Growth Factor (VEGF) 120, VEGF164 and Their Receptors in Bovine Granulosa Cells

“…These results suggest that the expression of VEGF genes induced by E2 may differ among isoforms in the GCs during follicle development in the bovine ovary. Estrogens increase the expression of VEGF mRNA by binding to the specific estrogen response elements in the VEGF gene [20] and have been shown to rapidly upregulate VEGF mRNA expression in the mouse [21], rat [22,23], and sheep [24] uterus and in cultured bovine GCs [25]. Therefore, our data suggests that the transcription of VEGF 120 but not VEGF 164 genes may be induced via estrogen receptors.…”

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

“…These findings are similar to those observed in other mammals. VEGF mRNA levels were elevated by estrogen in vivo in the mouse [37], rat [38,39] and ovine [40] uterus and in cultures of human endometrial glandular epithelial cells [36] and stromal cells [41,42]. In addition, Nayak and Brenner also showed that estrogen stimulated endometrial VEGF expression in vivo in ovariectomized rhesus monkeys [43].…”

FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

“…A role for FGFR-1 signaling in suppressing premature capacitation is plausible as bFGF has been identified in the uterus of many species including humans, monkeys, pigs, mice and rats (Ferriani et al, 1993;Gupta et al, 1997;Reynolds et al, 1998;Rider et al, 1997;Samathanam et al, 1998;Sangha et al, 1997;Wordinger et al, 1994). We hypothesize that binding of bFGF (or an equivalent ligand) to FGFR-1 leads to activation of the PI3K pathway and the subsequent phosphorylation of an as yet to be identified 'master controller of capacitation' (MCC) (Fig.…”