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. We proposed that uterine and ovarian remodeling during pregnancy is modulated by the conceptus. Color-Doppler ultrasonography, in situ macroscopy, histology, immunohistochemistry, and real time PCR were the techniques used throughout this work. Special attention was paid to conceptus modulation of the uterine vascular and architectural changes prior to implantation in equids and bovids. In mares, transient changes in endometrial vascularity accompanied conceptus location changes during the mobility phase. Continued presence of the conceptus in the same horn (7-min average) stimulated an increase in vascularity. After fixation, endometrial vascularity was higher in the endometrium surrounding the fixed conceptus, than in other areas of the ipsilateral horn, or in the opposite horn. Differential dorsal thickening of the endometrium preceded embryonic orientation. An early vascular indicator of the future position of the embryo proper was discovered. Orientation of the embryonic vesicle occurred immediately after fixation. Embryonic dysorientation was associated with a flaccid uterus and defective encroachment of the dorsal endometrium. Asymmetric enlargement of the allantoic sac spontaneously corrected dysorientation. The dorsal endometrium at the fixed conceptus site was edematous and richly vascularized, exhibiting a high density of blood vessels and endometrial glands. Adherence points were found between the yolk sac surface and the dorsal endometrium. Location of VEGF and VEGFR-1 did not differ between endometrium of pregnant and cyclic mares, and VEGFR-2 was absent or weak at the luminal epithelium of cyclic mares, but exhibited greater presence on Days 14 and 21 of pregnancy. Proliferation was intense at the luminal epithelium during estrus and practically absent during the luteal phase. During pregnancy, all endometrium presented proliferative cells. VEGF and VEGFR-2 mRNA expression was higher in pregnant mares than in cyclic. Uterine vascularity during early pregnancy in mares was mediated by conceptus presence. In heifers, uterine vascularity increased in nonpregnant animals temporally associated with the preovulatory rise in estradiol. In pregnant heifers, uterine vascularity increased in the horn ipsilateral to the conceptus from Days 19 to 40. Vascularity of the contralateral horn remained low until Day 32, when it began to rise, reaching vascularity approximately similar to the ipsilateral horn around Day 40. The increase in vascularity temporally paralleled allantoic sac development inside of each uterine horn. In mares, greater blood flow to the preovulatory follicle was associated with higher pregnancy rate. In cows, corpus luteum blood flow increased and decreased with individual PGFM pulses during spontaneous luteolysis. Induction of increased CL blood flow by prostaglandin did not assure the occurrence of luteolysis. In summary, these data provided insight into the architectural and molecular changes in the reproductive tract of equids and bovids. 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.
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