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Author(s): C. Tayade, Y. Fang and B. A. Croy
Publication Date: June 13, 2007
Reference: Journal of Reproduction and Development, Vol. 53, No. 3, 2007
Country: Canada

Summary:

In sows, the majority of fetal loss occurs in the implantation stage (G11-12), or later in mid-gestation. Angiogenesis must occur to provide nutrients to the growing fetuses, and can be done by increasing the surface area of the endometrial tissue or by increasing the density of blood vessels. VEGF binds to one of its two receptors on the maternal-fetal interface, and is responsible for endothelium cell proliferation, migration, and capillary permeability. Studying receptors for VEGF is complicated by the existence of a human, soluble VEGF-RI, and by PIGF which also binds VEGF-RI. Porcine endometrial cells have 2-3 times as many uterine natural killer cells (uNK), and studies on the purpose of this have mostly been performed for species other than porcine. Endometrial lymphocytes also contribute to angiogenesis, as indicated by VEGF and PIGF. In arresting conceptuses the levels of VEGF were lower, or not present, in lymphocytes; whereas, PIGF became elevated when failure was occurring. Increased PIGF could increase bioavailable VEGF, or help maturation of uNK cells. The level of transcription of either VEGF receptor was unchanged in conceptuse, but levels of VEGF-RI were higher in healthy sites to begin with. Endometrial endothelial cells attach to capillaries and make the blood-tissue interface, as well, they contribute to angiogenesis, provide paracrine signals for stem cell and organ development, and activate proliferation. Endothelial cells migrate by releasing degrading enzymes into the surrounding matrix, and moving into the opened area. Endothelial cells have increased PIGF and VEGF when pregnancy is occuring, and in fetal arrest VEGF transcription declines, but PIGF remains constant. Both receptors are transcribed, although VEGF-RII is done so at a higher level indicating endothelial cells and lymphocytes have different responses to VEGF. Porcine trophoblast research is limited, but in other species contributes to blood vessel development through angiogenesis, anti-angiogenesis, and vasoactive factors. Trophoblasts release the cytokines IFN-γ and IFN-δ, which are likely targeted to endometrial cells and could help activate and recruit lymphocytes. Trophoblasts transcribe higher VEGF than PIGF, but still at a lower level than lymphocytes. VEGF-RII is transcribed more than VEGF-RI, and VEGF-RI varies depending on gestation date, but does not vary during conceptuse failure. VEGF, PIGF, and VEGF-RII all decreased during conceptuse failure. Trophoblasts likely release stress signals to lymphocytes, which then withdraw angiogenesis and result in conceptuse failure. Lymphocytes, endothelial cells, and trophoblasts contribute to angiogenesis through transcription of VEGF, PIGF, VEGF-RI, and VEGF-RII. Angiogenesis is responsible for providing nutrients to conceptuses, and changes in transcription can indicate or contribute to pregnancy failure.

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