Conceptus-mediated endometrial vascular changes during early pregnancy in mares: an anatomic, histomorphometric, and vascular endothelial growth factor receptor system immunolocalization and gene expression study.

The research investigates how a developing embryo or conceptus influences the changes in endometrial tissue and blood vessel growth in mares during early pregnancy, before implantation occurs.

Research Methodology

• Researchers conducted macroscopic examinations of the uterus on day 21 of pregnancy, focusing on the dorsal endometrium that overlies the yolk sac.
• The team observed the stromal area taken up by blood vessels and the increase in the number of endometrial glands during early pregnancy.
• They analyzed the morphology of the endometrial tissue, along with the gene expression and location of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2), and Ki-67 on days 14 and 21 of pregnancy, day 10 of the estrous cycle, and during estrus via immunolocalization and quantitative RT-PCR techniques.

Main Findings

• Results indicated that the areas where endometrial encroachment occurs are restricted to specific regions.
• The research found no meaningful differences in the localization of VEGF and VEGFR1 proteins in pregnant versus non-pregnant mares; however, they discovered changes in the staining patterns of VEGFR2 and Ki-67.
• VEGFR2 was found in the luminal and glandular epithelium of pregnant mares, but was not present in the luminal epithelium of mares in the estrous cycle.
• Ki-67 staining, an indicator of cell proliferation, was weaker during the luteal phase but showed prominent staining in the luminal epithelium during estrus. In pregnant mares, all endometrial layers showed positive Ki-67 staining.
• The researchers discovered higher levels of VEGF mRNA, which drive vasculogenesis, during pregnancy.
• Additionally, on day 21 of pregnancy, there was a significant increase in the abundance of VEGFR2 transcript, which is associated with the growth of new blood vessels.

Conclusion

• The study concludes that the conceptus in mares plays an active role in directing the formation of new blood vessels within the uterus— a process known as vasculogenesis, establishing hemotrophic nutrition, a necessary condition for a successful pregnancy post implantation.