A decrease in uterine receptivity after fresh IVF transfers compared to frozen transfers has been documented, however the underlying mechanisms are unknown. A recently developed rat ovarian hyperstimulation (OH) model provides a novel mechanism to study endometrial changes caused by IVF drugs.
Distinct morphological and biochemical changes in luminal uterine epithelial cells (UECs) allow blastocyst implantation. These include a loss of microvilli, deepening of tight junctions (TJs), loss of adherens junctions (AJs), disappearance of focal adhesions (FAs) and increased tortuosity of the basal plasma membrane. This study investigated these changes in UECs at the time of implantation after OH to determine how this contributes to the decrease in uterine receptivity.
Ultrastructural studies of UECs at the time of implantation in OH rats show microvilli protruding from the apical surface, similar to day 1 of normal pregnancy. While there is no glycocalyx, we also note a lack of apical ADAM17, a sheddase required for cleavage of large molecules (eg HB-EGF) in preparation for blastocyst implantation.
Laterally, the AJ is retained and the TJs do not deepen at the time of implantation in OH rats as in normal pregnancy. While there is no change in occludin at this time between normal and OH pregnancy, there is a loss of claudin-4 after OH, suggesting a change in the permeability of the paracellular pathway.
At the time of implantation during OH pregnancy, the basal plasma membrane is flattened and contains numerous FAs with fewer morphological caveolae. There is a corresponding increase in paxillin, a focal adhesion protein, and a decrease in caveolin-1, a protein of morphological caveolae.
Collectively, these morphological and biochemical differences between ‘receptive’ UECs after OH compared to normal pregnancy provides a mechanism for the decrease in uterine receptivity immediately following fresh stimulated IVF cycles.