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

Abstract

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.

Concurrent Expression of VEGF-C and Neuropilin-2 Is Correlated with Poor Prognosis in Glioblastoma

“…It is interesting that NRP2 expression was associated with gender difference in our experiment, suggesting that NRP2 expression may be regulated by the sex hormones. Previous studies have demonstrated that NRP2 mRNA was decreased by estrogen in animal models (Walter et al 2010), which was consistent with our observation to some extent and may partially elucidate why male patients had higher NRP2 expression in our experiment. However, the underlying mechanisms of the correlation between NRP2 expression and sex hormone level is still misty.…”

Follistatin is essential for normal postnatal development and function of mouse oviduct and uterus

“…Transgenic mice were slightly older because tghFST315 mice do not demonstrate mating behaviour until ,8 wks of age (Lin et al 2008). Following bilateral ovariectomy, mice were left for a minimum of 7 days to recover and to allow for endometrial regression, before one of two steroid hormone protocols commenced (Heryanto and Rogers 2002;Walter et al 2005Walter et al , 2010Girling et al 2007). Protocol 1 (short-term oestrogen, E): mice were given a single subcutaneous (s.c.) injection of oestradiol-17b (100 ng in 100 mL peanut oil; Sigma-Aldrich, St Louis, MO, USA) or vehicle (100 mL peanut oil) 8 days post-ovariectomy (n ¼ 7-9 per group).…”

Mapping of estradiol binding sites through receptor micro-autoradiography in the endometrial stroma of early pregnant mice

“…Estrogen regulates several angiogenic factors in the mouse uterus, including Angiopoietin-2 and VEGF (Walter et al 2010;Guo et al 2012). Furthermore, similar to human decidual cells (Gibson et al 2013), mouse decidual cells are able to synthesize estrogen during pregnancy, which is critical for endometrial angiogenesis.…”