scholarly journals Expression and localization of vascular endothelial growth factor and its receptors in pig corpora lutea during the oestrous cycle

Reproduction ◽  
2003 ◽  
pp. 393-405 ◽  
Author(s):  
U Boonyaprakob ◽  
JE Gadsby ◽  
V Hedgpeth ◽  
P Routh ◽  
GW Almond
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Northern Blot ◽  
Luteal Phase ◽  
Northern Blot Analysis ◽  
Corpora Lutea ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Endothelial Growth Factor

Expression and localization of mRNAs for vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt) and VEGF receptor 2 (KDR) (VEGFR-1 and VEGFR-2, respectively) were investigated in pig corpora lutea. Northern blot analysis of total RNA indicated hybridization of pig VEGF, VEGFR-1 and VEGFR-2 cDNA probes to mRNA transcripts of approximately 3.9, 7.0 and 5.0 kb, respectively. The expression of mRNAs for VEGF and its receptors during the luteal phase (days 4, 7, 10, 13 and 15 after the onset of oestrus) were assessed by northern blot analysis, and hybridization signals were normalized to expression of pig 18S rRNA. Relative hybridization signals of expression of VEGF mRNA appeared to be constant; however, expression of VEGFR-1 mRNA was low on day 4, increased on day 7, and was higher on days 10, 13 and 15 (P<0.05, compared with day 4). In contrast, no changes in expression of mRNA for VEGFR-2 were evident on days 4-13, but a decrease was detected (P<0.05) at day 15. In situ hybridization revealed that VEGF mRNA was localized predominantly in large luteal cells, whereas both VEGFR-1 and VEGFR-2 were localized to small cells. These data indicate that the VEGF system may be involved in the regulation of luteal vasculature throughout the lifespan of the corpus luteum. Although the expression of VEGF mRNA was unchanged during the luteal phase, variations in the expression of VEGFR-1 and VEGFR-2 mRNAs indicate that differential regulation of expression of the VEGF receptors may play a role in the control of VEGF-mediated vascular growth at different phases of development and maturation of the pig corpus luteum.

scholarly journals Angiogenesis in the Human Corpus Luteum: Localization and Changes in Angiopoietins, Tie-2, and Vascular Endothelial Growth Factor Messenger Ribonucleic Acid1

2000 ◽  
Vol 85 (11) ◽  
pp. 4302-4309 ◽  
Author(s):  
Christine Wulff ◽  
Helen Wilson ◽  
Pawlina Largue ◽  
W. Colin Duncan ◽  
David G. Armstrong ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Corpora Lutea ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Messenger Ribonucleic Acid ◽  
Endothelial Growth Factor

In the menstrual cycle, extensive angiogenesis accompanies luteinization. During luteolysis, endothelial cells die, whereas in a conceptual cycle, the corpus luteum (CL) persists, and endothelial cell survival is extended. A main stimulator for angiogenesis is vascular endothelial growth factor (VEGF), while the angiopoietins (Ang-1 and Ang-2) may be important modulators. The aim of this study was to investigate the localization of Ang-1, Ang-2, their common receptor Tie-2, and VEGF messenger ribonucleic acid (mRNA) at the different stages of the functional luteal phase and after rescue by hCG. Ang-1 mRNA was uniformly expressed at a low level throughout the CL. The signal was highest during the early luteal phase. In contrast, Ang-2 mRNA expression was localized strongly to individual granulosa and thecal luteal and endothelial cells. Administration of hCG was associated with an increase in the Ang-2 mRNA area of expression and grain density in individual luteal and endothelial cells. The Tie-2 receptor mRNA was localized in endothelial cells, and the area of expression was highest during the early luteal phase and during luteal rescue. VEGF mRNA was found exclusively in granulosa luteal cells, and the area of expression was highest in corpora lutea during simulated pregnancy. These results begin to characterize the molecular regulation of the divergent processes involved in luteal angiogenesis during luteinization, luteolysis, and rescue in the human and imply that the angiopoietins are involved during the initial angiogenic phase and in luteal rescue.

Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney

1995 ◽  
Vol 268 (2) ◽  
pp. F240-F250 ◽  
Author(s):  
M. Simon ◽  
H. J. Grone ◽  
O. Johren ◽  
J. Kullmer ◽  
K. H. Plate ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Collecting Duct ◽  
Human Kidney ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Adult Kidney ◽  
Peritubular Capillaries ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) may modulate vascular permeability, chemotaxis for monocytes, and protease activity. In addition, VEGF may play a role in embryonic and tumor angiogenesis. In fetal mouse kidney, VEGF mRNA and protein expression have been demonstrated. This finding led to the hypothesis that VEGF might be involved in renal growth and development. To further elucidate the role of VEGF in human kidney, expression of VEGF and its receptors, the specific tyrosine kinase receptors, fit-1 and KDR, were studied. In fetal (6-24 gestational wk; mesonephros and metanephros) and adult kidney, VEGF mRNA and protein could be colocalized in glomerular epithelia and collecting duct cells by in situ hybridization and immunohistology. By reverse transcription-polymerase chain reaction, mRNA of three VEGF isoforms, VEGF121, VEGF165, and VEGF189, were found in fetal kidney and cortex, isolated glomeruli, and medulla of adult human kidney. KDR and flt-1 mRNA were coexpressed in endothelia of glomeruli and in peritubular capillaries in fetal and adult kidney. These data support the assumption that VEGF and its receptors may influence renal ontogenesis. We speculate that the constitutive expression of VEGF in adult kidney may be required for the function of VEGF receptor positive-fenestrated endothelia in glomeruli and postglomerular vessels. The expression of VEGF in collecting duct and of its receptors in medullary capillaries may in addition be relevant for maintaining medullary osmolality.

scholarly journals The Vascular Endothelial Growth Factor (VEGF)/VEGF Receptor 2 Pathway Is Critical for Blood Vessel Survival in Corpora Lutea of Pregnancy in the Rodent

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1301-1311 ◽  
Author(s):  
Samuel A. Pauli ◽  
Hongyan Tang ◽  
Jeff Wang ◽  
Peter Bohlen ◽  
Robert Posser ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Life Span ◽  
Critical Role ◽  
Corpora Lutea ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Luteal Function ◽  
Endothelial Growth Factor

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway regulates proliferation, survival, and permeability of vasculature. This pathway is active during the formation of a corpus luteum, a highly vascularized, endocrine organ with a short life span during the nonpregnant state. In the pregnant state, the life span of corpora lutea is much longer because they play a critical role in supporting pregnancy development. We hypothesized that the VEGF/VEGFR-2 pathway plays a critical role in regulating angiogenic events in the corpora lutea of pregnancy. Injection of the neutralizing anti-VEGFR-2 antibody DC101 (ImClone Systems, Inc., New York, NY) on embryonic d 3.5 (preimplantation) or 6.5 (postimplantation) disrupts function of the corpora lutea of pregnancy in CD1 mice, as evidenced by a decrease in organ size, regression of luteal vessels, and a fall in progesterone secretion within 24 h postinjection. Inhibition of the VEGFR-2 caused removal of endothelial cells, mostly through endothelial cell detachment from the vascular basement membrane. Luteal steroid-producing epithelial cells were eliminated through apoptosis secondary to vasculature becoming dysfunctional. Disruption of luteal function caused arrest of embryonic development. The effect of antibody is specific to the ovary, because pregnancy progresses normally in ovariectomized, progesterone-replaced animals treated with anti-VEGFR-2 antibody. Embryonic blood vessels were not affected directly by the antibody, because it did not reach the embryo. Administration of an antibody against VE-cadherin (E4G10), which specifically blocks endothelial proliferation, did not disrupt luteal function and pregnancy development. Thus, VEGFR-2-mediated endothelial cell signals are critical to maintain functionality of luteal blood vessels during pregnancy. Potential clinical applications of inhibitors of the VEGF/VEGFR-2 pathway include emergency contraception and medical treatment of ectopic and abnormal intrauterine pregnancies.

scholarly journals Localization and Quantification of Cyclic Changes in the Expression of Endocrine Gland Vascular Endothelial Growth Factor in the Human Corpus Luteum

2005 ◽  
Vol 90 (1) ◽  
pp. 427-434 ◽  
Author(s):  
Hamish M. Fraser ◽  
Julie Bell ◽  
Helen Wilson ◽  
Paul D. Taylor ◽  
Kevin Morgan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Prokineticin 2 ◽  
Endothelial Growth Factor ◽  
Human Corpus Luteum

Abstract Angiogenesis is essential for normal growth and function of the corpus luteum. The roles of various angiogenic factors in these events are being elucidated. Endocrine gland vascular endothelial growth factor (EG-VEGF) has recently been described in the human ovary. To define the localization of EG-VEGF mRNA in the corpus luteum and determine changes in its expression, dated human corpora lutea were studied at the early, mid-, and late luteal phases. Quantitative RT-PCR was employed to determine changes in EG-VEGF mRNA and compare expression to its related factor prokineticin-2 and the established angiogenic factor, VEGF. In situ hybridization was used to localize sites of production of EG-VEGF. To investigate whether expression of EG-VEGF was under the influence of LH or progesterone, luteinized granulosa cells were stimulated with human chorionic gonadotropin in the presence or absence of a progesterone synthesis inhibitor. EG-VEGF mRNA increased throughout the luteal phase, whereas there was no change in VEGF mRNA. The relative abundance of RNAs based upon PCR signal intensity showed that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2 was low. EG-VEGF mRNA was localized predominantly to granulosa-derived cells of the corpus luteum. Human chorionic gonadotropin stimulated both VEGF and EG-VEGF mRNA in vitro, but the level of expression was not influenced by progesterone. These results establish that in the human corpus luteum EG-VEGF is principally derived from granulosa lutein cells and that its synthesis is highest during the mid- to late luteal phase.

scholarly journals Mid-luteal angiogenesis and function in the primate is dependent on vascular endothelial growth factor

2001 ◽  
Vol 168 (3) ◽  
pp. 409-416 ◽  
Author(s):  
SE Dickson ◽  
R Bicknell ◽  
HM Fraser
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Luteal Phase ◽  
Smooth Muscle Actin ◽  
Proliferation Index ◽  
Endothelial Cell Proliferation ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is essential for the angiogenesis required for the formation of the corpus luteum; however, its role in ongoing luteal angiogenesis and in the maintenance of the established vascular network is unknown. The aim of this study was to determine whether VEGF inhibition could intervene in ongoing luteal angiogenesis using immunoneutralisation of VEGF starting in the mid-luteal phase. In addition, the effects on endothelial cell survival and the recruitment of periendothelial support cells were examined. Treatment with a monoclonal antibody to VEGF, or mouse gamma globulin for control animals, commenced on day 7 after ovulation and continued for 3 days. Bromodeoxyuridine (BrdU), used to label proliferating cells to obtain a proliferation index, was administered one hour before collecting ovaries from control and treated animals. Ovarian sections were stained using antibodies to BrdU, the endothelial cell marker, CD31, the pericyte marker, alpha-smooth muscle actin, and 3' end DNA fragments as a marker for apoptosis. VEGF immunoneutralisation significantly suppressed endothelial cell proliferation and the area occupied by endothelial cells while increasing pericyte coverage and the incidence of endothelial cell apoptosis. Luteal function was markedly compromised by anti-VEGF treatment as judged by a 50% reduction in plasma progesterone concentration. It is concluded that ongoing angiogenesis in the mid-luteal phase is primarily driven by VEGF, and that a proportion of endothelial cells of the mid-luteal phase vasculature are dependent on VEGF support.

Vascular endothelial growth factor-induced secretion of fibronectin is ERK dependent

2004 ◽  
Vol 286 (3) ◽  
pp. L539-L545 ◽  
Author(s):  
Altaf S. Kazi ◽  
Shidan Lotfi ◽  
Elena A. Goncharova ◽  
Omar Tliba ◽  
Yassine Amrani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Airway Remodeling ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Matrix Deposition ◽  
Endothelial Growth Factor

In severe asthma, cytokines and growth factors contribute to the proliferation of smooth muscle cells and blood vessels, and to the increased extracellular matrix deposition that constitutes the process of airway remodeling. Vascular endothelial growth factor (VEGF), which regulates vascular permeability and angiogenesis, also modulates the function of nonendothelial cell types. In this study, we demonstrate that VEGF induces fibronectin secretion by human airway smooth muscle (ASM) cells. In addition, stimulation of ASM with VEGF activates ERK, but not p38MAPK, and fibronectin secretion is ERK dependent. Both ERK activation and fibronectin secretion appear to be mediated through the VEGF receptor flt-1, as evidenced by the effects of the flt-1-specific ligand placenta growth factor. Finally, we demonstrate that ASM cells constitutively secrete VEGF, which is increased in response to PDGF, transforming growth factor-β, IL-1β, and PGE2. We conclude that ASM-derived VEGF, through modulation of the extracellular matrix, may play an important role in airway remodeling seen in asthma.

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