The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair
| العنوان: | The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair |
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| المؤلفون: | Jacqueline A. Maybin, Nikhil Hirani, Pamela Brown, Henry N. Jabbour, Hilary O. D. Critchley |
| المصدر: | The Journal of Clinical Endocrinology and Metabolism |
| بيانات النشر: | Endocrine Society, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Endocrinology, Diabetes and Metabolism, Biopsy, Clinical Biochemistry, Indomethacin, Endometrium, Dinoprost, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Hypoxia, Cells, Cultured, Progesterone, 0303 health sciences, 030219 obstetrics & reproductive medicine, Estradiol, Mifepristone, Middle Aged, Vascular endothelial growth factor, Vascular endothelial growth factor A, medicine.anatomical_structure, Female, medicine.symptom, medicine.drug, Adult, medicine.medical_specialty, Stromal cell, Prostaglandin, Biology, 03 medical and health sciences, Young Adult, Hormone Antagonists, Arteriole, Internal medicine, medicine.artery, medicine, Endocrine Research, Humans, Regeneration, Cyclooxygenase Inhibitors, RNA, Messenger, Menstrual Cycle, 030304 developmental biology, Biochemistry (medical), Hypoxia (medical), Hypoxia-Inducible Factor 1, alpha Subunit, chemistry |
| الوصف: | Context: The human endometrium has an exceptional capacity for repeated repair after menses, but its regulation remains undefined. Premenstrually, progesterone levels fall and prostaglandin (PG) F2α synthesis increases, causing spiral arteriole constriction. We hypothesized that progesterone withdrawal, PGF2α, and hypoxia increase vascular endothelial growth factor (VEGF), an endometrial repair factor. Design and Results: Endometrial biopsies were collected (n = 47) with ethical approval and consent. VEGF mRNA, quantified by quantitative RT-PCR, was increased during menstruation (P < 0.01).VEGF protein was maximally secreted from proliferative endometrial explants. Treatment of an endometrial epithelial cell line and primary human endometrial stromal cells with 100 nm PGF2α or hypoxia (0.5% O2) resulted in significant increases in VEGF mRNA and protein. VEGF was maximal when cells were cotreated with PGF2α and hypoxia simultaneously (P < 0.05–0.001). Secretory-phase endometrial explants also showed an increase in VEGF with cotreatment (P < 0.05). However, proliferative-phase explants showed no increase in VEGF on treatment with PGF2α and/or hypoxia. Proliferative tissue was induced to increase VEGF mRNA expression when exposed to progesterone and its withdrawal in vitro but only in the presence of hypoxia and PG. Hypoxia-inducible factor-1α (HIF-1α) silencing with RNA interference suppressed hypoxia-induced VEGF expression in endometrial cells but did not alter PGF2α-induced VEGF expression. Conclusions: Endometrial VEGF is increased at the time of endometrial repair. Progesterone withdrawal, PGF2α, and hypoxia are necessary for this perimenstrual VEGF expression. Hypoxia acts via HIF-1α to increase VEGF, whereas PGF2α acts in a HIF-1α-independent manner. Hence, two pathways regulate the expression of VEGF during endometrial repair. |
| اللغة: | English |
| تدمد: | 1945-7197 0021-972X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ca487acf55490cd9321367b20b260d94Test http://europepmc.org/articles/PMC3380090Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ca487acf55490cd9321367b20b260d94 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19457197 0021972X |
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