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Open AccessArticle

Vascular Endothelial Growth Factor A and VEGFR-1 Change during Preimplantation in Heifers

ETH Zurich, Animal Physiology, Institute of Agricultural Sciences, 8092 Zurich, Switzerland
Physiology Weihenstephan, Technical University of Munich, 85354 Freising, Germany
Bavarian State Research Center for Agriculture, Institute of Animal Breeding, 85586 Poing, Grub, Germany
ETH Zurich, Animal Nutrition, Institute of Agricultural Sciences, 8092 Zurich, Switzerland
Chair for Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians University, 81377 Munich, Germany
Vetsuisse Faculty Zurich, University of Zurich, Eschikon 27, AgroVet-Strickhof, 8315 Lindau (ZH), Switzerland
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(2), 544;
Received: 11 November 2019 / Revised: 8 January 2020 / Accepted: 9 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Embryo-Maternal Interactions Underlying Reproduction in Mammals)
Vascular endothelial growth factor A (VEGFA) plays a critical angiogenic role in the endometrium of placentalia during preimplantation. The role of VEGFA and its receptors is not fully characterised in bovine reproduction. We analysed the mRNA expression of VEGFA isoforms 121, 165 and 189, and VEGF receptors 1 and 2 in three experimental settings (A, B and C). We compared intercaruncular endometrium of cyclic to pregnant heifers at Days 12, 15 and 18 post insemination (Day 0), and between Day 15 and Day 18 conceptuses (A). We further compared caruncular versus intercaruncular endometrium at Day 15 (B), and endometrium of heifers carrying embryos originating from somatic cell nuclear transfer (SCNT) versus in vitro fertilisation (IVF) at Day 18 (C). Endometrial VEGFA protein was localised and quantified. Pregnant heifers displayed lower intercaruncular endometrial mRNA expression of VEGFA-121 (p = 0.045) and VEGFA-189 (p = 0.009) as well as lower VEGFA protein abundance (p < 0.001) at Day 15. The VEGFA protein was localised in intercaruncular luminal, glandular epithelium and in tunica muscularis of blood vessels. At Day 15, caruncular endometrium displayed higher VEGFA mRNA expression than intercaruncular endometrium (p < 0.05). Intercaruncular endometrial VEGFA protein at Day 18 was higher in abundance in SCNT than in IVF (p = 0.038). Therefore, during preimplantation in cattle, there may be a need for timely physiological reduction in intercaruncular endometrial VEGFA expression in favour of the caruncular area to facilitate a gradient towards the implantation sites. A higher expression of VEGFA in SCNT may predispose for later placentation abnormalities frequently observed following SCNT. View Full-Text
Keywords: angiogenesis; bovine; conceptus; endometrium; IVF; SCNT angiogenesis; bovine; conceptus; endometrium; IVF; SCNT
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Chiumia, D.; Hankele, A.-K.; Groebner, A.E.; Schulke, K.; Reichenbach, H.-D.; Giller, K.; Zakhartchenko, V.; Bauersachs, S.; Ulbrich, S.E. Vascular Endothelial Growth Factor A and VEGFR-1 Change during Preimplantation in Heifers. Int. J. Mol. Sci. 2020, 21, 544.

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