During early pregnancy the luminal uterine epithelial cells (UECs) undergo extensive remodelling to permit blastocyst implantation. An essential component of this Plasma Membrane Transformation is the loss of microvilli from the apical surface of UECs and a disorganisation of the associated actin-based terminal web.
Previous studies have indicated that uterine receptivity is impeded by the ovarian hyperstimulation (OH) procedure used during IVF. This study examined whether the microvilli and associated actin cytoskeleton are impacted by OH. In other cell types, overexpression of EPI64 protein disrupts apical microvilli and actin organisation. Therefore, this study examined changes in EPI64 during normal and OH pregnancy.
This study utilised rat models of normal and OH pregnancy to examine changes in UEC ultrastructural morphology and EPI64 abundance using transmission electron microscopy, correlative light and electron microscopy and western blotting.
At the time of fertilisation in both normal and OH pregnancy, UECs possess regular microvilli which are supported by an actin terminal web. However, at the time of implantation during OH pregnancy the UECs possess unusually large, branching microvilli that are not supported by a terminal web; in stark contrast to the flattened apical plasma membrane seen during normal pregnancy. Western blotting indicated a significantly greater abundance of EPI64 at the time of implantation during normal pregnancy compared to all other groups.
These results demonstrate a highly unusual uterine luminal surface in OH pregnancy at the time when a blastocyst would usually attach and implant. The presence of these unusual microvilli is expected to impede blastocyst attachment and implantation. The change in EPI64 abundance during normal pregnancy presents a potential mechanism for the loss of microvilli, which is also disrupted by the OH procedure. Together, these results provide a potential explanation for the reduction in uterine receptivity observed after OH.