Effect of Estrogen on Vascular Endothelial Growth/Permeability Factor Expression by Glandular Epithelial and Stromal Cells in the Baboon Endometrium1

Niklaus, Andrea L.; Aberdeen, Graham W.; Babischkin, Jeffery S.; Pepe, Gerald J.; Albrecht, Eugene D.

doi:10.1095/biolreprod.102.011288

Cited by 46 publications

(34 citation statements)

References 31 publications

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“…In addition, Nayak and Brenner also showed that estrogen stimulated endometrial VEGF expression in vivo in ovariectomized rhesus monkeys [43]. Therefore, combined with the present study, evidence supports that estrogen has a significant role in stimulating VEGF system expression by glandular, luminal epithelial and stromal cells of the endometrium to promote its angiogenesis and growth [44].…”

Section: Discussionsupporting

confidence: 85%

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Weng

Sheng

et al. 2012

Journal of Reproduction and Development

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Abstract. In this study, we investigated the immunoreactivity of vascular endothelial growth factor (VEGF) and its receptors flt-1 (VEGFR1) and the kinase domain receptor (KDR/Flk-1, VEGFR2) in the uteri of the wild ground squirrels during the estrous period, early pregnancy and nonbreeding period. Cellular localizations of VEGF, VEGFR1 and VEGFR2 were detected by immunohistochemistry, and total proteins were extracted from uterine tissue in the estrous period, early pregnancy and nonbreeding period for Western blotting analysis. In addition, plasma estradiol-17β and progesterone concentrations were measured by radioimmunoassay. Stronger positive staining of VEGF was found in luminal epithelial cells and glandular cells, and its receptors (VEGFR1 and VEGFR2) were observed in stromal cells in the estrous period and early pregnancy compared with the nonbreeding period. The protein levels of VEGF, VEGFR1 and VEGFR2 were significantly higher in the estrous period and early pregnancy as compared with the nonbreeding period. Besides, plasma estradiol-17β and progesterone concentrations were higher in the estrous period and early pregnancy than in the nonbreeding period, suggesting that the immunoreactivities of VEGF, VEGFR1 and VEGFR2 were correlated with changes in plasma estradiol-17β and progesterone concentrations. These results suggested that VEGF and its receptors may be involved in the regulation of seasonal changes in the uterine functions of wild female ground squirrels. Key words: Uterus, VEGF, VEGFR1, VEGFR2, Wild ground squirrel (J. Reprod. Dev. 58: [537][538][539][540][541][542][543] 2012) D uring the reproductive cycle, the uterine endometrium undergoes a precisely timed complex sequence of physiological and morphological changes in preparation for implantation. These changes are controlled primarily by the ovarian steroid hormones 17β-estradiol (E 2 ) and progesterone [1]. During pregnancy, blood flow to the uterus is increased dramatically to meet the rising demands of the growing fetus. Endocrine control of this phenomenon is complex but includes in part the action of many growth factors [2,3]. Vascular endothelial growth factor (VEGF) is a protein with angiogenic activity and a potent stimulator of microvascular permeability [4,5]. It plays an important role in physiological and pathological neovascularization via its receptors Flt1/VEGFR1 and kinase insert domain containing region (KDR)/VEGFR2, both of which have tyrosine kinase activity [6]. In reproductive organs, VEGF is required for normal ovarian angiogenesis and endometrial growth throughout the ovulatory cycle in humans [7,8] and rodents [9,10]. The expression of VEGF and its receptors has been demonstrated in the endometrium in humans and in experimental and domestic animals throughout the menstrual cycle, with an upregulation in the late proliferative and luteal phases [11][12][13][14][15], periods that correspond to angiogenesis and an increase in vascular permeability [16]. However, the expression of VEGF and its receptors VEGFR1 and V...

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Section: Discussionsupporting

confidence: 85%

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Weng

Sheng

et al. 2012

Journal of Reproduction and Development

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“…Vegfa expression increased in endometrial stromal cells within 2 h. By 24 h post-administration, there was no stromal Vegfa and expression was restricted to the epithelium. In the baboon and rhesus monkey, endometrial stromal and epithelial VEGFA expression was restored by E 2 treatment following a reduction after ovariectomy (Nayak & Brenner 2002, Niklaus et al 2003. In baboon endometrium, VEGFA mRNA levels were increased in both stromal and glandular epithlelium (measured in samples collected by laser capture microscopy) within 2 h of E 2 administration and remained elevated during the 6 h experiment (Aberdeen et al 2008).…”

Section: Vascular Endothelial Growth Factor-amentioning

confidence: 97%

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

Girling¹,

Rogers²

2009

Reproduction

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Angiogenesis, lymphangiogenesis and vascular maturation occur on a regular, physiological basis in human endometrium. These processes form part of a continuum of vascular remodelling involving numerous regulatory factors. Key factors include vascular endothelial growth factor (VEGF)A, VEGFC and VEGFD, and their associated receptors VEGFR1, VEGFR2 and VEGFR3. A second group of vascular regulatory proteins belongs to the angiopoietin (ANG)-TIE system. Although members of the VEGF family and the ANG-TIE system are represented in the endometrium, our understanding of how these different molecules interact to regulate remodelling of the blood and lymphatic vasculature present in the endometrium is still limited. A review of the current information is provided.

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“…In vivo research with various animal models has produced more variable results. In studies using baboons and rhesus monkeys, endometrial stromal and epithelial VEGFA mRNA levels were restored by E 2 following a reduction after ovariectomy (Nayak & Brenner 2002, Niklaus et al 2003. In contrast, another study found that there was a significantly higher amount of VEGFA mRNA in endometria of hypogonadal monkeys compared with E 2 -treated monkeys (Greb et al 1997).…”

Section: Introductionmentioning

confidence: 96%

Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus

Walter¹,

Rogers²,

Girling³

2010

Reproduction

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The angiogenic effects of 17b-oestradiol (E 2 ) in the mouse endometrium are mediated by vascular endothelial growth factor-A (VEGFA). We analysed the temporal and spatial changes in VEGFA isoform and (co)receptor expression in ovariectomised mouse uteri following E 2 treatment. VEGFA isoform and receptor mRNA were quantified in whole uterine tissue collected 2, 6, 12 and 24 h after E 2 or vehicle treatment. Laser capture microdissection was used to investigate mRNA expression in epithelial, stromal and myometrial tissues separately. Endothelial cell proliferation, VEGFA and VEGF receptor-2 (VEGFR2) protein were visualised using immunohistochemistry. Endometrial endothelial cell proliferation was only observed 24 h after E 2 treatment. In whole uterine tissue, total Vegfa, Vegfa 164 and Vegfa 120 mRNA expression increased 2 h post E 2 treatment, and then decreased by 24 h. Vegfa 188 expression was lower in E 2 -treated animals at all time points relative to control animals. Vegfr2 and neuropilin-1 (Nrp1) mRNA expression did not change following E 2 treatment; Nrp2 expression decreased by 24 h. When uterine compartments were considered separately at 24 h post E 2 or vehicle, stromal Vegfa 120 , Vegfa 188 and Vegfr2 mRNA expression and myometrial Vegfa 120 and Vegfa 188 mRNA expression were reduced in E 2 -treated mice relative to controls, whereas epithelial Vegfa 188 mRNA expression increased. The highest VEGFA immunoexpression was observed in luminal epithelium; expression increased at 24 h relative to other time points. No changes were noted in VEGFR2 immunoexpression among treatment groups. We have provided the first evidence that VEGFA isoform and receptor mRNA expression are differentially regulated by E 2 in different uterine cell compartments.

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Effect of Estrogen on Vascular Endothelial Growth/Permeability Factor Expression by Glandular Epithelial and Stromal Cells in the Baboon Endometrium1

Cited by 46 publications

References 31 publications

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Regulation of endometrial vascular remodelling: role of the vascular endothelial growth factor family and the angiopoietin–TIE signalling system

Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus

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