Mechanisms behind the decrease in uterine receptivity after fresh IVF transfers compared to frozen transfers are unknown. A 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 morphologically and biochemical changes in the apical and basolateral plasma membranes of 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 long, branched microvilli protruding from the apical surface in distinct contrast to the flattening of the apical surface at this time during normal pregnancy. Laterally, the AJ is retained and the TJs do not deepen at the time of implantation in OH rats as in normal pregnancy. The molecular composition of the TJs also change with a loss of claudin-4 at the time of implantation 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. This is in contrast to the tortuous basal plasma membrane with numerous caveolae seen at the time of receptivity during normal pregnancy.
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.