Blood Vessel Growth in the Endometrium

Goodger, Anne M.; Rogers, Peter A. W.

doi:10.3109/10739689509148277

Cited by 33 publications

(15 citation statements)

References 88 publications

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“…Angiogenesis and antiangiogenesis are prevalent during the cyclic events of the female reproductive cycle associated with follicular and luteal growth and apoptosis as well as endometrial proliferation and regression [3][4][5][6]. The molecular regulation of these processes is very poorly understood, and whether any aspects of regulation are unique to specific organs or tissues within the reproductive system is not known.…”

Section: Introductionmentioning

confidence: 99%

2-Methoxyestradiol, an Endogenous Estradiol Metabolite, Differentially Inhibits Granulosa and Endothelial Cell Mitosis: A Potential Follicular Antiangiogenic Regulator1

Shang

Konidari

Schomberg

2001

Biology of Reproduction

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2-Methoxyestradiol (2-ME) is an estradiol metabolite with antiangiogenic and antitumor activity. It is formed by granulosa cell (GC) catechol-O-methyltransferase activity and is present in the normal follicle at high concentrations. In this unique microenvironment, it may regulate selected cell types via autocrine and/or paracrine action. To assess the possibility that 2-ME or estradiol might exert differential mitotic and/or apoptotic effects on endothelial cells and GCs, we compared their actions on primary cultures of hormone- and/or growth factor-stimulated porcine GCs (pGCs) as well as two types of endothelial cells, primary cultures of porcine endothelial cells (pECs), and a spontaneously transformed rabbit endothelial vascular cell (REVC) line. The 2-ME, but not estradiol, dose dependently suppressed tritiated thymidine ((3)H-T) incorporation into epidermal growth factor (EGF)-stimulated REVCs and EGF/insulin (INS)-stimulated pECs. In contrast, 2-ME did not attenuate incorporation in FSH/INS-stimulated pGCs. It reduced incorporation by approximately 50% in EGF/INS-stimulated pGCs, indicating that responsiveness to 2-ME in normal cells can be modulated by hormone and growth factor treatment. Estradiol was not antimitotic to pGCs. As indicated by 4',6-diamido-2-phenylindole hydrochloride nuclear staining, estradiol was nonapoptotic in either cell type, and 2-ME significantly increased apoptosis of REVCs, but not of pGCs. In a cell migration assay, REVC movement was attenuated by 2-ME, but not by estradiol. In summary, the results show that antimitotic as well as proapoptotic responses to 2-ME vary with cell type and, in the case of pGC antimitotic activity, with the regulatory microenvironment. Thus, they provide a rationale for autocrine and/or paracrine action of 2-ME at its site of production in vivo, and they strongly support the concept of 2-ME as a candidate ovarian angiogenesis inhibitor.

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Section: Introductionmentioning

confidence: 99%

2-Methoxyestradiol, an Endogenous Estradiol Metabolite, Differentially Inhibits Granulosa and Endothelial Cell Mitosis: A Potential Follicular Antiangiogenic Regulator1

Shang

Konidari

Schomberg

2001

Biology of Reproduction

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“…However, ovarian steroids do not appear to control the angiogenic restoration of the vasculature of the functional endometrial layer (1,2). Although several angiogenic factors are present in human endometrium (3)(4)(5), most studies have focused on vascular endothelial growth factor (VEGF), which is expressed cyclically by endometrial stromal and glandular epithelial cells (6 -8).…”

mentioning

confidence: 98%

Differential Effects of Thrombin and Hypoxia on Endometrial Stromal and Glandular Epithelial Cell Vascular Endothelial Growth Factor Expression

Lockwood¹,

Krikun²,

Koo³

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

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Ovarian steroids and/or premenstrual endometrial hypoxia are thought to restore the endometrial vasculature shed during menstruation by elevating endometrial vascular endothelial growth factor (VEGF) levels. During the luteal phase, VEGF levels peak, progesterone induces estradiol (E(2))-primed human endometrial stromal cells (HESCs) to decidualize and express tissue factor (TF), and endometrial vascular permeability is enhanced. The latter would present circulating clotting factors to decidual cell-expressed TF to form local thrombin. HESCs were incubated in serum-supplemented medium containing vehicle (control) or 10(-8) M E(2) or 10(-7) M medroxyprogesterone acetate (MPA) or E(2) + MPA for 7 d to induce decidualization, while monolayers of human endometrial glandular epithelial cells (HEGECs) formed during 4-d incubation of glands. The medium was exchanged for a defined medium containing corresponding vehicle or steroids +/- thrombin under normoxia or hypoxia (0-1% O(2)). Hypoxia enhanced secreted immunoreactive VEGF levels by severalfold in HESCs and HEGECs, but the steroids did not affect VEGF output in either cell type under normoxia or hypoxia. In E(2) + MPA-decidualized HESCs, VEGF levels were elevated by 0.1 U/ml of thrombin, and 0.5-2.5 U/ml of thrombin elicited maximum effects. The addition of 0.5 U/ml of thrombin evoked a time-dependent enhancement of VEGF levels and about an 8-fold increase at 48 h (P < 0.02; n = 6). Northern blotting indicated that E(2) + MPA-decidualized HESCs expressed VEGF(121), VEGF(165), and VEGF(189) mRNA, which were enhanced severalfold during 5- to 20-h incubation with thrombin. Moreover, TRAP, a synthetic peptide activator of the constitutively expressed protease activated receptor-1 thrombin receptor in decidualized HESCs, also elevated secreted VEGF levels. By contrast, HEGECs were unresponsive to thrombin added alone or with ovarian steroids. These results suggest that thrombin formed by progestin-augmented TF levels acts as an autocrine enhancer of VEGF expression in decidualized HESCs. Because angiogenesis occurs in a matrix of decidualized HESCs, these in vitro results provide a novel mechanism to account for both the peak in VEGF and angiogenesis in luteal phase human endometrium.

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“…The extracellular matrix is then degraded allowing endothelial cell migration into the surrounding area. Activated endothelial cells also initiate proliferation and form tubes that construct the new blood vessel meshwork [45]. Endothelial cells are major components of uterine stroma.…”

Section: Endometrial Endothelial Cells and Implantation Site Angiogenmentioning

confidence: 99%

A Review of Gene Expression in Porcine Endometrial Lymphocytes, Endothelium and Trophoblast During Pregnancy Success and Failure

Tayade

Yuan

Croy

2007

Journal of Reproduction and Development

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Abstract. Meat pig breeds used commercially in North America lose significant numbers of geneticallynormal fetuses in the peri-implantation (attachment) period and at mid-gestation (day 50 of the114 day gestation interval). Fetal demand that is in excess to the placental blood supply is thought to underlie these waves of fetal loss. In many species, the endometrium of early normal pregnancy is enriched in innate immune cells, particularly uterine natural killer (uNK) cells. In pigs, a species with epitheliochorial placentation, conceptuses mediate about a three-fold enrichment in uNK cells at attachment sites but the functions of these cells are unknown. In species with hemochorial placentation, uNK cells are highly enriched during the process of decidualization and promote endometrial angiogenesis. We have conducted molecular analyses using pure samples of endometrial lymphocytes or endothelium and trophoblast from healthy and arresting conceptus attachment sites in Yorkshire gilts immediately post-attachment [gestation day (GD) 20] and at mid pregnancy (GD50). In healthy sites, angiogenesis was more robustly promoted by lymphocytes than by trophoblasts. An early sign of impending fetal arrest was loss of vascular endothelial growth factor (VEGF) transcription from the lymphocytes and elevation in transcription of the pro-inflammatory gene Interferon (IFN)-γ. We have postulated that newly differentiated endometrial endothelial cells, not fetal trophoblasts, are damaged by the maternal withdrawal of vascular support and onset of inflammation and that this endometrial damage contributes significantly to peri-implantation fetal death.

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Blood Vessel Growth in the Endometrium

Cited by 33 publications

References 88 publications

2-Methoxyestradiol, an Endogenous Estradiol Metabolite, Differentially Inhibits Granulosa and Endothelial Cell Mitosis: A Potential Follicular Antiangiogenic Regulator1

2-Methoxyestradiol, an Endogenous Estradiol Metabolite, Differentially Inhibits Granulosa and Endothelial Cell Mitosis: A Potential Follicular Antiangiogenic Regulator1

Differential Effects of Thrombin and Hypoxia on Endometrial Stromal and Glandular Epithelial Cell Vascular Endothelial Growth Factor Expression

A Review of Gene Expression in Porcine Endometrial Lymphocytes, Endothelium and Trophoblast During Pregnancy Success and Failure

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