Enhanced Endometrial Repair and Fertility with HEO Complex: Insights from In Vivo Mouse Models

Enhanced Endometrial Repair and Fertility with HEO Complex: Insights from In Vivo Mouse Models

To elucidate the mechanisms underlying the beneficial effects of the HEO complex on endometrial repair and fertility, we conducted a series of in vivo experiments using mouse models.

Integration of Human Endometrial Cells into Mouse Endometrium

Following injection of HEO and EO complexes into mice, we observed distinct cellular localization patterns at different time points. At day 3 post-injection, human endometrial epithelial and stromal cells from the HEO complex remained relatively independent within the mouse uterine cavity. Notably, cells in the HEO graft exhibited expression of human-specific markers, including CK7, Vimentin, and CD31, confirming their human origin. In contrast, the EO graft lacked human-specific CD31 expression.

By day 7 post-injection, a remarkable integration of human endometrial epithelial cells from both HEO and EO complexes into the mouse endometrium was evident. Human-specific CK7-positive epithelial cells were detected within the mouse subendometrial tissue, indicating successful engraftment and fusion with the host tissue. These integrated epithelial cells also expressed human-specific estrogen and progesterone receptors, suggesting their potential functionality within the mouse hormonal milieu.

These findings demonstrate the active participation of HEO complex cells in the reconstruction of the damaged mouse endometrium, corroborating the observed improvements in endometrial repair and fertility following HEO complex transplantation.

Formation of Functional Human Blood Vessels within Mouse Grafts

To further investigate the impact of HEO complex on vascularization, we subcutaneously injected the complex into mice. After 14 days, we observed the formation of a rich network of blood vessels within the grafts using stereomicroscopy. To assess the functionality of these vessels, we employed in vivo imaging techniques.

Intravenous injection of human-specific and mouse-specific fluorescent markers revealed a direct connection between the human blood vessel network within the grafts and the mouse vasculature. Furthermore, injection of fluorescently labeled dextran resulted in the visualization of red fluorescent signal within the green-labeled human blood vessels, confirming active perfusion of mouse blood through the human vasculature in the grafts.

In contrast, subcutaneous injection of the EO complex led to graft shrinkage and the formation of inflammatory vesicles, highlighting the superior angiogenic potential of the HEO complex. The formation of functional blood vessels by the HEO complex likely contributes to its ability to promote endometrial repair and enhance fertility, as vascularization is essential for graft survival, integration, and function.

Conclusion

Our findings provide compelling evidence for the multifaceted mechanisms by which HEO complex improves endometrial repair and fertility. The successful integration of human endometrial cells into the mouse endometrium, coupled with the formation of functional human blood vessels, highlights the therapeutic potential of this approach for addressing endometrial dysfunction and infertility.