Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct.

Pedro Pinto-Bravo,Rosário P Roberto Da Costa,Graça Ferreira-Dias,António Galvão,Graça Alexandre-Pires,Carina Fernandes,Maria Rosa Rebordão,Dariusz J Skarzynski,Elisabete Silva,Pedro Pessa-Santos,Ana Amaral

doi:10.3390/ani11041099

Abstract

Simple SummaryThe oviduct provides the ideal conditions for fertilization and early embryonic development. Adequate vascularization is essential for proper oviduct physiological function. In this work on the mare oviduct, differences in the oviductal artery and arterioles and their ramifications in the infundibulum, ampulla and isthmus were examined. Locally, vascularization is modulated by the action of angiogenic factors, mediated by their specific receptors. In the present study, the isthmus presented the largest vascular area and the highest number of vascular structures in the follicular phase. We have also shown that the relative abundance of angiogenic transcripts and proteins, such as fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all portions of the oviduct throughout the estrous cycle. There was an increase in the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus, and of FGF2 and KDR in the isthmus. This was also observed in the isthmus, where the relative abundance of proteins FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (FGF1, FGF2, VEGF) and their receptors—FGFR1, FGFR2, KDR, respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares’ oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest number of vascular structures in the follicular phase. Transcripts (qPCR) and relative protein abundance (Western blot) of angiogenic factors fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all oviduct portions throughout the estrous cycle. Upregulation of the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus and of FGF2 and KDR in the isthmus were noted. Furthermore, in the isthmus, the relative protein abundance of FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its three portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.

Highlights

In the mammalian female, the oviduct bridges the ovary to the uterus
To the best of our knowledge, the present work shows for the first time that the area and number of microvascular structures may show changes in specific regions of the mare oviduct, according to estrous cycle phases
In an attempt to understand the observed changes in microvascular density in equine oviduct, and due to the importance of angiogenesis in reproductive organs, the expression of the most important angiogenic factors and receptors were evaluated in the mare oviduct

Summary

Introduction

The oviduct bridges the ovary to the uterus. In addition to the physical transport of the gametes and embryo, the oviduct provides paracrine signaling and biophysical support for sperm selection, capacitation and hyperactivation, fertilization, early preimplantation development and remodeling the epigenetic landscape of the embryo [1,2,3,4,5]. In addition to providing adequate vascularization to the female reproductive tract, angiogenesis is crucial for the regulation of physiological processes related to reproductive function [7,8]. Angiogenesis consists on the growth of blood vessels from the existing vasculature, which occurs throughout the lifetime in both healthy conditions and in disease [7,9]. It is worth noting that in the fallopian tubes of women, during early pregnancy recognition, anti-angiogenic genes are upregulated [29]

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