Vascular endothelial growth factor system in the cow oviduct: A possible involvement in the regulation of oviductal motility and embryo transport

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic and permeability enhancing factor, which shows the highest activity in the oviduct during the periovulatory period of the estrous cycle in cattle. It has also been shown that the contraction activity of oviduct is highest during the periovulatory period. The present study therefore focused on the possible involvement of VEGF in the regulation of biosynthesis and secretion of contraction-relaxation-related substances in the cow oviduct. Possible autonomous VEGF system in the oviduct as well as its endocrine control was also studied. Bovine oviductal epithelial cells (BOEC) in the second passage were cultured with VEGF (1 ng/ml) alone or with luteinizing hormone (LH; 10 ng/ml), estradiol 17-beta (E2; 1 ng/ml), and/or progesterone (P4; 1 ng/ml). The levels of prostaglandins (PGs), endothelin-1 (ET-1), and angiotensin II (Ang II) in the medium were measured using second antibody enzymeimmunoassay (EIA). The mRNA expressions for cycloxygenase-2 (Cox-2), prostaglandin F synthase (PGFS), prostaglandin E synthase (PGES), prepro-ET-1, endothelin converting enzyme-1 (Ece-1), angiotensin converting enzyme-1 (Ace-1), VEGF and its receptors were investigated using real-time RT-PCR. The results indicate that, (1) VEGF dose-dependently stimulated the release of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), and ET-1, but not Ang II. VEGF and VEGF with LH, E2, and P4 upregulated mRNA expression for biosynthesis cascade of PG, ET-1 as well as their release. However, only the combination of VEGF with LH, E2, and P4 upregulated mRNA for Ace-1 and Ang II release, but not VEGF alone. (2) Treatments of LH, with E2 and/or P4 increased the mRNA expression for VEGF, Flk-1 and Flt-1, and (3) VEGF itself downregulated the expression of mRNA for VEGF, and LH, E2, and P4 enhanced this downregulatory effect. The results of the present study provide the first evidence that (1) VEGF directly stimulates the biosynthesis and release of PGE2, PGF2alpha, and ET-1 in the bovine oviduct, (2) LH stimulates the oviductal VEGF system, and (3) VEGF downregulates the oviductal VEGF system and this downregulation was further intensified in the presence of LH. The data suggest that the preovulatory LH-surge, together with increasing E2 secretion from the Graffian follicle and basal P4 levels from the regressing corpus luteum (CL), upregulates the oviductal VEGF system, inducing the maximum oviductal production of contraction-relaxation-related substances for active oviduct contraction and rapid transport of gametes to the fertilization site. However, the oviductal VEGF elevation caused by the LH-surge, appears to downregulate the oviductal VEGF system immediately after ovulation thereby may contribute to suppress oviductal contraction to secure slow transport of the embryo to the uterus at the optimal time.

Angiotensin II Secretion by the Bovine Oviduct is Stimulated by Luteinizing Hormone and Ovarian Steroids

“…The lack of significant elevation of the ACE-1 mRNA level when Ang II release is increased during the follicular phase is difficult to explain; however, it has been reported that E2 induces hepatic angiotensinogen synthesis and release [26,27] and that the plasma rennin concentration is higher during estrus [28] in rats. Thus, the elevated precursor levels in the oviducts coincident with the elevated systemic E2 levels during the follicular phase could be attributed to increased Ang II release without significant rise in the ACE-1 mRNA level.Previously, we have shown that LH activates a system of various vasoactive peptides in the bovine oviduct, including ET-1 [8], vascular endothelial growth factor (VEGF) [29] and tumor necrosis factor α (TNFα) [7,8]. In the present study, we also observed that LH upregulates ACE-1 mRNA expression in cultured OECs and that LH stimulates the release of Ang II in both microdialysis and cell culture.…”

N-acetylglucosaminyltransferase I Activity of Bovine Oviduct Epithelial Cells: Stimulation by Luteinizing Hormone, Vascular Endothelial Growth Factor and Tumor Necrosis Factor .ALPHA.

“…The local content of VEGF in the bovine oviduct is at its highest during the periovulatory period [8], and may be responsible for the higher fluid secretion within the oviduct during this period [24]. Moreover, we recently reported that VEGF may contribute to regulation of the different contractile patterns of the oviduct, which occur during the period of gamete and embryo transport [15]. TNFα and its receptors are highly expressed in the cow oviduct during the periovulatory period, and may act to optimize the release of contraction-related substances during this period [13].…”

“…I n t h e f e m a l e r e p r o d u c t i v e s y s t e m , t h e appropriate biological activity of VEGF and TNFα are crucial for the cascade of events that produce a successful pregnancy [8,13,15,[21][22][23]. The local content of VEGF in the bovine oviduct is at its highest during the periovulatory period [8], and may be responsible for the higher fluid secretion within the oviduct during this period [24].…”

“…We also investigated the possible modulation of bovine oviductal GnT I activity by vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) α, which are produced at their highest levels during the periovulatory period and regulate oviduct functions [13][14][15].…”

The gonadotropins: Tissue-specific angiogenic factors?

“…This downregulation was further intensified in the presence of LH (Wijayagunawardane et al, 2005). The periovulatory stage was associated with the highest contraction acitivity of the oviduct and the LH-VEGF interrelation might regulate oviductual contraction to assure an optimal transport of the oocyte through the oviduct by regulation contraction.…”