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Nadia Alfaidy - One of the best experts on this subject based on the ideXlab platform.
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EG-VEGF Maintenance Over Early Gestation to Develop a Pregnancy-Induced Hypertensive Animal Model
2018Co-Authors: Déborah Reynaud, Frédéric Sergent, Mohamed Benharouga, Sophie Brouillet, Roland Abi Nahed, Nadia AlfaidyAbstract:During the last decade, multiple animal models have been developed to mimic hallmarks of pregnancy-induced hypertension (PIH) diseases, which include gestational hypertension, preeclampsia (PE), or eclampsia. Converging in vitro, ex vivo, and clinical studies from our group strongly suggested the potential involvement of the new angiogenic factor EG-VEGF (Endocrine Gland-derived-VEGF) in the development of PIH. Here, we described the protocol that served to demonstrate that maintenance of EG-VEGF production over 11.5 days post coitus (dpc) in the gravid mice caused the development of PIH. The developed model exhibited most hallmarks of preeclampsia.
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Sustained Endocrine Gland–Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension
Hypertension, 2016Co-Authors: Frédéric Sergent, Jean-jacques Feige, Mohamed Benharouga, Pascale Hoffmann, Sophie Brouillet, Vanessa Garnier, Aude Salomon, Padma Murthi, Nadia AlfaidyAbstract:Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine Gland–derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
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PROK1 Level in the Follicular Microenvironment: A New Noninvasive Predictive Biomarker of Embryo Implantation
Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Nadia Alfaidy, Pascale Hoffmann, Pierre Gillois, Aurore Gueniffey, Camille Lebayle, Héloïse Garçin, Claire Thomas-cadi, Julien Bessonnat, Charles Coutton, Laure VillaretAbstract:Prokineticin 1 (PROK1), also called Endocrine Gland-derived vascular endothelial growth factor, is a well-established regulator of endometrial receptivity and placental development. However, its clinical usefulness as a noninvasive predictive biomarker of embryo implantation is yet to be validated.
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eg vegf a key Endocrine factor in placental development
Trends in Endocrinology and Metabolism, 2012Co-Authors: Sophie Brouillet, Jean-jacques Feige, Pascale Hoffmann, Nadia AlfaidyAbstract:Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key Endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF.
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expression pattern of prokineticin 1 and its receptors in bovine ovaries during the estrous cycle involvement in corpus luteum regression and follicular atresia
Biology of Reproduction, 2007Co-Authors: Tatiana Kisliouk, Qunyong Zhou, Nadia Alfaidy, Aharon Friedman, Eyal Klipper, D Schams, Rina MeidanAbstract:Abstract Prokineticin 1 (PROK1), also termed Endocrine Gland-derived vascular endothelial growth factor (Endocrine Gland-derived VEGF), is a newly identified protein assigned with diverse biologic functions. It binds two homologous G protein-coupled receptors, PROKR1 and PROKR2. To better understand the roles of PROK1 and its receptors in ovarian function, their expression was determined in follicles and corpora lutea (CLs) at different developmental stages. PROK1 mRNA levels were low at early luteal stage and midluteal stage, but increased sharply during natural or induced luteolysis. High PROK1 mRNA levels also were found in atretic follicles. This profile of PROK1 expression was opposite to that of the well-established angiogenic factor VEGF. Of the two receptor-type expressions, PROKR1 but not PROKR2 was correlated positively with its ligand. Immunohistochemical staining revealed that PROK1 was located mainly within the muscular layer of arterioles, and during regression it also was localized to macro...
Napoleone Ferrara - One of the best experts on this subject based on the ideXlab platform.
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bv8 and Endocrine Gland derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Jennifer Lecouter, Constance H Zlot, Max L Tejada, Franklin Peale, Napoleone FerraraAbstract:Bv8 and Endocrine-Gland-derived VEGF (EG-VEGF), or prokineticins, are two highly related, secreted proteins that we previously described as selective angiogenic mitogens. Here we describe the expression and functional characterization of Bv8 in peripheral blood cells, notably monocytes, neutrophils, and dendritic cells, and in the bone marrow. In human and mouse, the two Bv8 G protein-coupled receptors are expressed in hematopoietic stem cells and specific mature blood cells, including lymphocytes. Bv8 is highly expressed by neutrophils at sites of inflammation and can stimulate migration of monocytes, in a pertussis toxin-sensitive manner. Bv8, or EG-VEGF that shares the same receptors, increased numbers of colony-forming units granulocytic and monocytic in cultures of human or mouse hematopoietic stem cells. Systemic in vivo exposure to Bv8 or EG-VEGF resulted in significant increases in total leukocyte, neutrophil, and monocyte counts. Additionally, adenovirus (Av)Bv8 or AvEG-VEGF delivered just before 5-fluorouracil injury promoted the survival of hematopoietic cells and enhanced progenitor mobilization. In conclusion, Bv8 can promote survival and differentiation of the granulocytic and monocytic lineages. Bv8 potentially modulates growth, survival, and function of cells of the innate and adaptive immune systems, possibly through autocrine or paracrine signaling mechanisms.
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human Endocrine Gland derived vascular endothelial growth factor expression early in development and in leydig cell tumors suggests roles in normal and pathological testis angiogenesis
The Journal of Clinical Endocrinology and Metabolism, 2004Co-Authors: Michel Samson, Gretchen Frantz, Franklin Peale, Nathalie Riouxleclercq, Ewa Rajpertde Meyts, Napoleone FerraraAbstract:Angiogenesis is essential for tumor growth and metastasis. A new human angiogenic mitogen, Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF), has been recently identified; its expression pattern is restricted to Endocrine Glands, with the highest expression in testis. We used in situ hybridization and newly generated monoclonal antibodies to investigate the expression of EG-VEGF in normal human prenatal and adult testis and in 48 human testicular tumors of different subtypes. We found that EG-VEGF was expressed from 14 wk until birth in human fetal testis. In the adult testis, EG-VEGF was strongly expressed only in Leydig cells. In testicular tumors, EG-VEGF was expressed specifically in Leydig cell tumors, whereas germ cell-derived neoplasms, including carcinoma in situ, seminoma, and nonseminomatous germ cell tumors, were negative for this antigen. In contrast, VEGF, another powerful angiogenic factor, was expressed in seminoma, but very weakly in Leydig cell tumors. Interestingly, we found that Leydig cell tumors presented vessel surface density 3.2-fold higher than seminoma. These findings argue that human EG-VEGF may play a role in angiogenesis both during the early Endocrine development of testis and in the adult testis as well as in Leydig cell tumor growth.
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mouse Endocrine Gland derived vascular endothelial growth factor a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ specific angiogenesis
Endocrinology, 2003Co-Authors: Jennifer Lecouter, Rui Lin, Zemin Zhang, Gretchen Frantz, Kenneth J Hillan, Napoleone FerraraAbstract:We recently described human Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF) as an endothelial cell mitogen with a novel selective activity and an expression pattern essentially limited to steroidogenic Glands. Herein we present the identification and characterization of the mouse ortholog. The mouse cDNA and predicted amino acid sequences are, respectively, 86% and 88% identical with the human. Surprisingly, the mouse EG-VEGF transcript is predominantly expressed in liver and kidney. A comparison of human and mouse EG-VEGF promoter sequences revealed a potential binding site for NR5A1, which is known to be a pivotal element for steroidogenic-specific transcription, in the human but not mouse promoter. In situ hybridization studies localized expression of mouse EG-VEGF mRNA to hepatocytes and renal tubule cells. Interestingly, capillary endothelial cells in these sites share several common structural features with those found in steroidogenic Glands. Within liver and kidney, EG-VEGF receptor expression was largely restricted to endothelial cells. Mouse EG-VEGF promoted proliferation and survival of endothelial cells. We propose that mouse EG-VEGF, like human EG-VEGF, plays a role in regulating the phenotype and growth properties of endothelial cells within distinct capillary beds.
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differential expression of the angiogenic factor genes vascular endothelial growth factor vegf and Endocrine Gland derived vegf in normal and polycystic human ovaries
American Journal of Pathology, 2003Co-Authors: Napoleone Ferrara, Jennifer Lecouter, Lisa Dillardtelm, Gretchen Frantz, Thinh Pham, Aparna Draksharapu, Thomas J Giordano, Franklin PealeAbstract:Angiogenesis is a key aspect of the dynamic changes occurring during the normal ovarian cycle. Hyperplasia and hypervascularity of the ovarian theca interna and stroma are also prominent features of the polycystic ovary syndrome (PCOS), a leading cause of infertility. Compelling evidence indicated that vascular endothelial growth factor (VEGF) is a key mediator of the cyclical corpus luteum angiogenesis. However, the nature of the factor(s) that mediate angiogenesis in PCOS is less clearly understood. Endocrine Gland-derived (EG)-VEGF has been recently identified as an endothelial cell mitogen with selectivity for the endothelium of steroidogenic Glands and is expressed in normal human ovaries. In the present study, we compared the expression of EG-VEGF and VEGF mRNA in a series of 13 human PCOS and 13 normal ovary specimens by in situ hybridization. EG-VEGF expression in normal ovaries is dynamic and generally complementary to VEGF expression in both follicles and corpora lutea. A particularly high expression of EG-VEGF was detected in the Leydig-like hilus cells found in the highly vascularized ovarian hilus. In PCOS ovaries, we found strong expression of EG-VEGF mRNA in theca interna and stroma in most of the specimens examined, thus spatially related to the new blood vessels. In contrast, VEGF mRNA expression was most consistently associated with the granulosa cell layer and sometimes the theca, but rarely with the stroma. These findings indicate that both EG-VEGF and VEGF are expressed in PCOS ovaries, but in different cell types at different stages of differentiation, thus suggesting complementary functions for the two factors in angiogenesis and possibly cyst formation.
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the Endocrine Gland derived vegf homologue bv8 promotes angiogenesis in the testis localization of bv8 receptors to endothelial cells
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Jennifer Lecouter, Rui Lin, Gretchen Frantz, Max L Tejada, Franklin Peale, Kenneth J Hillan, Napoleone FerraraAbstract:We recently identified an angiogenic mitogen, Endocrine-Gland-derived vascular endothelial growth factor (EG-VEGF), with selective activity for endothelial cells of Endocrine tissues. Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF. The human and mouse Bv8 genes share a common structure. Like EG-VEGF, Bv8 is able to induce proliferation, survival and migration of adrenal cortical capillary endothelial cells. Bv8 gene expression is induced by hypoxic stress. Bv8 expression occurs predominantly in the testis and is largely restricted to primary spermatocytes. Adenoviral delivery of Bv8 or EG-VEGF to the mouse testis resulted in a potent angiogenic response. We have localized the expression of the Bv8/EG-VEGF receptors within the testis to vascular endothelial cells. The testis exhibits relatively high turnover of endothelial cells. Therefore, Bv8 and EG-VEGF, along with other factors such as VEGF-A, may maintain the integrity and also regulate proliferation of the blood vessels in the testis.
Jennifer Lecouter - One of the best experts on this subject based on the ideXlab platform.
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bv8 and Endocrine Gland derived vascular endothelial growth factor stimulate hematopoiesis and hematopoietic cell mobilization
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Jennifer Lecouter, Constance H Zlot, Max L Tejada, Franklin Peale, Napoleone FerraraAbstract:Bv8 and Endocrine-Gland-derived VEGF (EG-VEGF), or prokineticins, are two highly related, secreted proteins that we previously described as selective angiogenic mitogens. Here we describe the expression and functional characterization of Bv8 in peripheral blood cells, notably monocytes, neutrophils, and dendritic cells, and in the bone marrow. In human and mouse, the two Bv8 G protein-coupled receptors are expressed in hematopoietic stem cells and specific mature blood cells, including lymphocytes. Bv8 is highly expressed by neutrophils at sites of inflammation and can stimulate migration of monocytes, in a pertussis toxin-sensitive manner. Bv8, or EG-VEGF that shares the same receptors, increased numbers of colony-forming units granulocytic and monocytic in cultures of human or mouse hematopoietic stem cells. Systemic in vivo exposure to Bv8 or EG-VEGF resulted in significant increases in total leukocyte, neutrophil, and monocyte counts. Additionally, adenovirus (Av)Bv8 or AvEG-VEGF delivered just before 5-fluorouracil injury promoted the survival of hematopoietic cells and enhanced progenitor mobilization. In conclusion, Bv8 can promote survival and differentiation of the granulocytic and monocytic lineages. Bv8 potentially modulates growth, survival, and function of cells of the innate and adaptive immune systems, possibly through autocrine or paracrine signaling mechanisms.
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mouse Endocrine Gland derived vascular endothelial growth factor a distinct expression pattern from its human ortholog suggests different roles as a regulator of organ specific angiogenesis
Endocrinology, 2003Co-Authors: Jennifer Lecouter, Rui Lin, Zemin Zhang, Gretchen Frantz, Kenneth J Hillan, Napoleone FerraraAbstract:We recently described human Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF) as an endothelial cell mitogen with a novel selective activity and an expression pattern essentially limited to steroidogenic Glands. Herein we present the identification and characterization of the mouse ortholog. The mouse cDNA and predicted amino acid sequences are, respectively, 86% and 88% identical with the human. Surprisingly, the mouse EG-VEGF transcript is predominantly expressed in liver and kidney. A comparison of human and mouse EG-VEGF promoter sequences revealed a potential binding site for NR5A1, which is known to be a pivotal element for steroidogenic-specific transcription, in the human but not mouse promoter. In situ hybridization studies localized expression of mouse EG-VEGF mRNA to hepatocytes and renal tubule cells. Interestingly, capillary endothelial cells in these sites share several common structural features with those found in steroidogenic Glands. Within liver and kidney, EG-VEGF receptor expression was largely restricted to endothelial cells. Mouse EG-VEGF promoted proliferation and survival of endothelial cells. We propose that mouse EG-VEGF, like human EG-VEGF, plays a role in regulating the phenotype and growth properties of endothelial cells within distinct capillary beds.
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differential expression of the angiogenic factor genes vascular endothelial growth factor vegf and Endocrine Gland derived vegf in normal and polycystic human ovaries
American Journal of Pathology, 2003Co-Authors: Napoleone Ferrara, Jennifer Lecouter, Lisa Dillardtelm, Gretchen Frantz, Thinh Pham, Aparna Draksharapu, Thomas J Giordano, Franklin PealeAbstract:Angiogenesis is a key aspect of the dynamic changes occurring during the normal ovarian cycle. Hyperplasia and hypervascularity of the ovarian theca interna and stroma are also prominent features of the polycystic ovary syndrome (PCOS), a leading cause of infertility. Compelling evidence indicated that vascular endothelial growth factor (VEGF) is a key mediator of the cyclical corpus luteum angiogenesis. However, the nature of the factor(s) that mediate angiogenesis in PCOS is less clearly understood. Endocrine Gland-derived (EG)-VEGF has been recently identified as an endothelial cell mitogen with selectivity for the endothelium of steroidogenic Glands and is expressed in normal human ovaries. In the present study, we compared the expression of EG-VEGF and VEGF mRNA in a series of 13 human PCOS and 13 normal ovary specimens by in situ hybridization. EG-VEGF expression in normal ovaries is dynamic and generally complementary to VEGF expression in both follicles and corpora lutea. A particularly high expression of EG-VEGF was detected in the Leydig-like hilus cells found in the highly vascularized ovarian hilus. In PCOS ovaries, we found strong expression of EG-VEGF mRNA in theca interna and stroma in most of the specimens examined, thus spatially related to the new blood vessels. In contrast, VEGF mRNA expression was most consistently associated with the granulosa cell layer and sometimes the theca, but rarely with the stroma. These findings indicate that both EG-VEGF and VEGF are expressed in PCOS ovaries, but in different cell types at different stages of differentiation, thus suggesting complementary functions for the two factors in angiogenesis and possibly cyst formation.
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the Endocrine Gland derived vegf homologue bv8 promotes angiogenesis in the testis localization of bv8 receptors to endothelial cells
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: Jennifer Lecouter, Rui Lin, Gretchen Frantz, Max L Tejada, Franklin Peale, Kenneth J Hillan, Napoleone FerraraAbstract:We recently identified an angiogenic mitogen, Endocrine-Gland-derived vascular endothelial growth factor (EG-VEGF), with selective activity for endothelial cells of Endocrine tissues. Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF. The human and mouse Bv8 genes share a common structure. Like EG-VEGF, Bv8 is able to induce proliferation, survival and migration of adrenal cortical capillary endothelial cells. Bv8 gene expression is induced by hypoxic stress. Bv8 expression occurs predominantly in the testis and is largely restricted to primary spermatocytes. Adenoviral delivery of Bv8 or EG-VEGF to the mouse testis resulted in a potent angiogenic response. We have localized the expression of the Bv8/EG-VEGF receptors within the testis to vascular endothelial cells. The testis exhibits relatively high turnover of endothelial cells. Therefore, Bv8 and EG-VEGF, along with other factors such as VEGF-A, may maintain the integrity and also regulate proliferation of the blood vessels in the testis.
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Endocrine Gland–derived VEGF and the emerging hypothesis of organ-specific regulation of angiogenesis
Nature Medicine, 2002Co-Authors: Jennifer Lecouter, Rui Lin, Napoleone FerraraAbstract:The diversity in growth and morphological characteristics among endothelial cells in different normal tissues and tumors has been long recognized. Yet there has been no clear molecular explanation for such diversity at the level of vascular endothelial growth factor A (VEGF-A) and other established regulators of angiogenesis that are expressed widely and show little tissue selectivity in their angiogenic properties. Endocrine Gland–derived VEGF represents the first example of a tissue-specific angiogenic factor, likely to be followed by others.
Jean-jacques Feige - One of the best experts on this subject based on the ideXlab platform.
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Sustained Endocrine Gland–Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension
Hypertension, 2016Co-Authors: Frédéric Sergent, Jean-jacques Feige, Mohamed Benharouga, Pascale Hoffmann, Sophie Brouillet, Vanessa Garnier, Aude Salomon, Padma Murthi, Nadia AlfaidyAbstract:Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine Gland–derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
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eg vegf bv8 and their receptor expression in human bronchi and their modification in cystic fibrosis impact of cftr mutation delf508
American Journal of Physiology-lung Cellular and Molecular Physiology, 2015Co-Authors: Jean-jacques Feige, Wael Traboulsi, Sylvain Chauvet, Laura Thevenon, Amal KouadriAbstract:Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, Endocrine Gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have b...
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eg vegf a key Endocrine factor in placental development
Trends in Endocrinology and Metabolism, 2012Co-Authors: Sophie Brouillet, Jean-jacques Feige, Pascale Hoffmann, Nadia AlfaidyAbstract:Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key Endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF.
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Mitogenic functions of Endocrine Gland-derived vascular endothelial growth factor and Bombina variegata 8 on steroidogenic adrenocortical cells.
Journal of Endocrinology, 2008Co-Authors: Michelle Keramidas, Caroline Faudot, Agnès Cibiel, Jean-jacques Feige, Michaël ThomasAbstract:Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF) and its homolog Bombina variegata (Bv8), also termed prokineticin-1 and -2 (PK1 and PK2) respectively, are newly identified peptides with specific mitogenic activity on Endocrine Gland-derived endothelial cells. In the present study, we analyzed the sites of expression of EG-VEGF/PK1, Bv8/PK2, and their receptors (PKR1 and PKR2) in the adrenal cortex and checked for new biological functions of these factors on the Endocrine cell compartment. RT-PCR and immunostaining analyses revealed that glomerulosa and fasciculata cells express both factors and both receptors. EG-VEGF/PK1 had no effect on the steroidogenic activity of both bovine glomerulosa and fasciculata cells but appeared to be mitogenic for both cell types. Binding of EG-VEGF/PK1 to fasciculata cells stimulated the phosphorylation of ERK1/2. Pretreatment with pertussis toxin suppressed this effect, indicating that it was Gi mediated. EG-VEGF/PK1 also increased the phosphorylation of Akt in Endocrine cells of the adrenal cortex. EG-VEGF/PK1 and Bv8/PK2 thus represent new regulatory peptides acting as autocrine mitogens for Endocrine cells.
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Expression and oxygen regulation of Endocrine Gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy.
Endocrinology, 2006Co-Authors: Pascale Hoffmann, Jean-jacques Feige, Nadia AlfaidyAbstract:Angiogenesis is a key process of dynamic tissue remodeling occurring during placentation. Compelling evidence indicates that vascular endothelial growth factor (VEGF) is an important mediator of placental angiogenesis and appears to be deregulated in preeclampsia. Recently a new angiogenic factor, Endocrine Gland-derived VEGF (EG-VEGF), also known as prokineticin 1 (PK1), has been identified, and its expression was shown to be restricted to Endocrine Glands, including the placenta. In this study we investigated the pattern of expression of EG-VEGF, its related factor Bv8/PK2, and their common receptors, PKR1 and PKR2, in human placenta during the first trimester of pregnancy. We also examined EG-VEGF and PKR1 regulation by oxygen tension in isolated trophoblast cells (TCs). Our results show that EG-VEGF, but not Bv8/PK2, is expressed in human placenta. EG-VEGF is mainly localized to the syncytiotrophoblast layer with the highest expression detected between the 8th and 10th wk of gestation. EG-VEGF expression within placental villi is different from that of VEGF, which is mainly localized in the cytotrophoblast and extravillous trophoblast cells. In TCs, PKR1 mRNA is about 80 times more abundant than PKR2 mRNA. Both EG-VEGF and PKR1 mRNAs appear to be regulated by hypoxia. These findings suggest that EG-VEGF has a direct effect on TCs via its receptor PKR1 and is likely to play an important role in human placentation. The expression pattern of EG-VEGF, its regulation by oxygen tension, and its complementary localization to that of VEGF suggest that this new factor might also be deregulated in preeclampsia.
Pascale Hoffmann - One of the best experts on this subject based on the ideXlab platform.
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Sustained Endocrine Gland–Derived Vascular Endothelial Growth Factor Levels Beyond the First Trimester of Pregnancy Display Phenotypic and Functional Changes Associated With the Pathogenesis of Pregnancy-Induced Hypertension
Hypertension, 2016Co-Authors: Frédéric Sergent, Jean-jacques Feige, Mohamed Benharouga, Pascale Hoffmann, Sophie Brouillet, Vanessa Garnier, Aude Salomon, Padma Murthi, Nadia AlfaidyAbstract:Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine Gland–derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
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sustained Endocrine Gland derived vascular endothelial growth factor levels beyond the first trimester of pregnancy display phenotypic and functional changes associated with the pathogenesis of pregnancy induced hypertension
Hypertension, 2016Co-Authors: Frédéric Sergent, Mohamed Benharouga, Pascale Hoffmann, Sophie Brouillet, Vanessa Garnier, Aude Salomon, Padma MurthiAbstract:Pregnancy-induced hypertension diseases are classified as gestational hypertension, preeclampsia, or eclampsia. The mechanisms of their development and prediction are still to be discovered. Endocrine Gland–derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor secreted by the placenta during the first trimester of human pregnancy that was shown to control trophoblast invasion, to be upregulated by hypoxia, and to be abnormally elevated in pathological pregnancies complicated with preeclampsia and intrauterine growth restriction. These findings suggested that sustaining EG-VEGF levels beyond the first trimester of pregnancy may contribute to pregnancy-induced hypertension. To test this hypothesis, osmotic minipumps delivering EG-VEGF were implanted subcutaneously into gravid OF1 (Oncins France 1) mice on day 11.5 post coitus, which is equivalent to the end of the first trimester of human pregnancy. Mice were euthanized at 15.5 and 18.5 days post coitus to assess (1) litter size, placental, and fetal weights; (2) placental histology and function; (3) maternal blood pressure; (4) renal histology and function; and (5) circulating soluble fms-like tyrosine kinase 1 and soluble endoglin. Increased EG-VEGF levels caused significant defects in placental organization and function. Both increased hypoxia and decreased trophoblast invasion were observed. Treated mice had elevated circulating soluble fms-like tyrosine kinase 1 and soluble endoglin and developed gestational hypertension with dysregulated maternal kidney function. EG-VEGF effect on the kidney function was secondary to its effects on the placenta as similarly treated male mice had normal kidney functions. Altogether, these data provide a strong evidence to confirm that sustained EG-VEGF beyond the first trimester of pregnancy contributes to the development of pregnancy-induced hypertension.
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PROK1 Level in the Follicular Microenvironment: A New Noninvasive Predictive Biomarker of Embryo Implantation
Journal of Clinical Endocrinology and Metabolism, 2016Co-Authors: Nadia Alfaidy, Pascale Hoffmann, Pierre Gillois, Aurore Gueniffey, Camille Lebayle, Héloïse Garçin, Claire Thomas-cadi, Julien Bessonnat, Charles Coutton, Laure VillaretAbstract:Prokineticin 1 (PROK1), also called Endocrine Gland-derived vascular endothelial growth factor, is a well-established regulator of endometrial receptivity and placental development. However, its clinical usefulness as a noninvasive predictive biomarker of embryo implantation is yet to be validated.
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eg vegf a key Endocrine factor in placental development
Trends in Endocrinology and Metabolism, 2012Co-Authors: Sophie Brouillet, Jean-jacques Feige, Pascale Hoffmann, Nadia AlfaidyAbstract:Endocrine Gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key Endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF.
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Expression and oxygen regulation of Endocrine Gland-derived vascular endothelial growth factor/prokineticin-1 and its receptors in human placenta during early pregnancy.
Endocrinology, 2006Co-Authors: Pascale Hoffmann, Jean-jacques Feige, Nadia AlfaidyAbstract:Angiogenesis is a key process of dynamic tissue remodeling occurring during placentation. Compelling evidence indicates that vascular endothelial growth factor (VEGF) is an important mediator of placental angiogenesis and appears to be deregulated in preeclampsia. Recently a new angiogenic factor, Endocrine Gland-derived VEGF (EG-VEGF), also known as prokineticin 1 (PK1), has been identified, and its expression was shown to be restricted to Endocrine Glands, including the placenta. In this study we investigated the pattern of expression of EG-VEGF, its related factor Bv8/PK2, and their common receptors, PKR1 and PKR2, in human placenta during the first trimester of pregnancy. We also examined EG-VEGF and PKR1 regulation by oxygen tension in isolated trophoblast cells (TCs). Our results show that EG-VEGF, but not Bv8/PK2, is expressed in human placenta. EG-VEGF is mainly localized to the syncytiotrophoblast layer with the highest expression detected between the 8th and 10th wk of gestation. EG-VEGF expression within placental villi is different from that of VEGF, which is mainly localized in the cytotrophoblast and extravillous trophoblast cells. In TCs, PKR1 mRNA is about 80 times more abundant than PKR2 mRNA. Both EG-VEGF and PKR1 mRNAs appear to be regulated by hypoxia. These findings suggest that EG-VEGF has a direct effect on TCs via its receptor PKR1 and is likely to play an important role in human placentation. The expression pattern of EG-VEGF, its regulation by oxygen tension, and its complementary localization to that of VEGF suggest that this new factor might also be deregulated in preeclampsia.