The corpora lutea proangiogenic state of VEGF system components is turned to antiangiogenic at the later phase of the oestrous cycle in cows

Abstract

Blood vessel expansion and reduction in the corpus luteum (CL) is regulated by the vascular endothelial growth factor (VEGF) system and linked to the maintenance of the CL. The VEGF system has both angiogenic and antiangiogenic ligands and receptors. Our objective was to evaluate the relationship between the mRNA expression of angiogenic and antiangiogenic members of the VEGF system in the CL, throughout the luteal phase of the oestrous cycle in cows. The CL of 18 cows were collected by transvaginal surgery on days 4, 6, 9, 12, 15 and 18 of the oestrous cycle and the mRNA expression of VEGF system components was evaluated by quantitative real-time PCR. The mRNA expression of VEGF ligands and receptors increased (P < 0.05) from the early-and mid-luteal phase (days 4 to 12) reaching its maximum expression on day 15 of the cycle. We found no expression of VEGF164b throughout the cycle. Expression of sVEGFR1 did not change during the oestrous cycle and exceeded that of the VEGFR1 by 100 times. Nonetheless, as VEGFR1 increased, the relationship between the soluble and membrane receptor decreased (P < 0.01). In contrast, the expression of VEGFR2 was higher than that of its soluble isoform for all days studied, however, the ratio between the membrane-bound and its soluble counterpart decreased continuously throughout the cycle (P < 0.01). Our results show that the expression levels for VEGF ligands, receptors and their antagonistic counterparts are adjusted during CL development and regression, to upregulate angiogenesis early in the oestrous cycle and restrict it at the time of luteolysis.

Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles

“…VEGFA is a potent mitogen that promotes the growth, migration and permeability of vascular endothelial cells in CLs throughout the luteal phase (Robinson et al 2007). Levels of this protein within the CL peak at around day 15 of the oestrous cycle but decline on luteolysis as witnessed in this study (Table 5) and by Guzmán et al (2015). This latter study also demonstrated that there are both pro-and anti-angiogenic isoforms of VEGFA in the bovine CL, and that immediately before luteolysis, there is an increase in anti-angiogenic isoforms.…”

“…This latter study also demonstrated that there are both pro-and anti-angiogenic isoforms of VEGFA in the bovine CL, and that immediately before luteolysis, there is an increase in anti-angiogenic isoforms. With respect to the various isoforms identified by Guzmán et al (2015), we can deduce from the primers designed for this study that we amplified the single isoform 205, which has only been described as pro-angiogenic. Increased expression of this isoform in group A CLs, relative to group B and C CLs, further serves to confirm their viability.…”

Co‐ordinated expression of the VEGF system components in granulosa cells to develop a proangiogenic autocrine milieu during ovarian follicle development

“…This is interesting, as Yamamoto, Rundqvist, Branco, and Johnson () determined that VEGF164 was the most potent VEGF isoform to reduce apoptosis and stimulate cell migration and proliferation. In agreement with the above, we previously found that the bovine corpus luteum expressed VEGF164a during development, but had no expression for VEGF164b (Guzmán et al, ). Therefore, the lack of expression of VEGF164b indicates that the mechanism that regulates the biological actions of VEGFxxx ligands in the bovine ovary is different from that observed in the murine and human tissues.…”

“…Transgenic mice, overexpressing VEGF165b in the ovary show lower fertility and increased follicle atresia (Qiu et al, ). Similarly, in the bovine corpus luteum, the expression of mRNA for VEGF120a is higher than that for VEGF120b during its development and this relationship was inverted before luteolysis (Guzmán, Macías‐Valencia, Fierro‐Fierro, Gutiérrez, & Rosales‐Torres, ). These results indicate that a balance between angiogenic and antiangiogenic isoforms is needed for normal follicle and corpus luteum development.…”

“…Indeed, we have previously found that the relationship in the expression of VEGFR2 and sVEGFR2 mRNA is high during the growing phase of the corpora lutea and diminishes before luteolysis. In contrast, the VEGFR1/sVEGFR1 ratio is low during the growing phase of the CL and increases at luteolysis (Guzmán et al, ). Thus, the increase in VEGFR1 may attenuate VEGF actions on angiogenesis and cell survival.…”