Local Effect of the Conceptus on Uterine Vascular Perfusion and Remodeling during Early Pregnancy in Mares - New Findings by Doppler Ultrasonography

Background: The mammalian reproductive tract is the only organ system in the body where entire tissue layers and structures are in physiologically dynamic and cyclic changes. Angiogenesis is well known to be critical to assure blood supply for tissue growth and remodeling. Ovarian-produced steroids control reproductive tract remodeling, and cyclic rhythmicity of the hypothalamic-ovarian axis. Review: We have proposed that uterine remodeling during pregnancy is modulated by the conceptus. Special attention was paid to conceptus modulation of the uterine vascular and architectural changes prior to implantation in equids. Our studies using Doppler ultrasonography have described vascular and morphological endometrial changes during early pregnancy in mares. The most important vascular changes observed were: 1) Transient changes in endometrial vascular perfusion accompany the embryonic vesicle as the vesicle changes location during embryo mobility. 2) The continued presence of the vesicle in the same horn for an average of 7 min stimulated an increase in vascularity of the endometrium of the middle segment of the horn during mobile phase. 3) After fixation, endometrial vascularity was progressively higher in the following sequence: horn without the vesicle, horn with the vesicle, and area of endometrium surrounding the fixed vesicle. 4) After fixation, an early vascular indicator of the future position of the embryo proper was discovered by color-Doppler imaging and consisted of a colored spot in the image of the endometrium close to the wall of the embryonic pole. In addition to the observed vascular changes, morphological changes also were observed. They are related to asymmetrical encroachment of the uterine wall, resulting from differential thickening of the upper turgid uterine wall at the mesometrial attachment, in which is normally observed in mares after embryonic vesicle fixation. The thickening of the endometrium was studied during mobile phase and after fixation, and the thickness of the endometrium at the mesometrial aspect of the vesicle divided by the thickness at the antimesometrial aspect was termed the encroachment ratio. The most important morphological changes observed were: 1) Differential dorsal thickening of the endometrium that surrounds the embryonic vesicle began during the later days of the mobility phase. 2) After fixation, the differential dorsal thickening or endometrial encroachment upon the vesicle increased rapidly and was more than four times thicker than ventrally by 3 days after fixation. 3) The increase in vascularity began before the increase in the encroachment ratio in the endometrium at the site of future fixation. 4) The increase in the encroachment ratio between 1 and 3 days after fixation was more rapid than during -4 to 0 days before fixation. 5) Embryonic vesicle dysorientation was associated with a flaccid uterus and defective encroachment of the dorsal endometrium. 6) Asymmetric enlargement of the allantoic sac spontaneously corrected the disorientation of the embryo proper in mares with apparently normal uterine tone and endometrial encroachment, so that orientation of the umbilical cord attachment was at a normal position near 12 o’clock. Conclusion: Our data provided insight into the architectural and vascular changes in the reproductive tract of equids. These results set the stage for future experiments to understand more completely the role of the conceptus in regulating the uterine environment in favor of its development.