The Mechanism of FOXO1 Nuclear Translocation during Embryo Implantation

On average one in every four couples worldwide struggle with infertility. Dysregulation of the progesterone receptor (PGR) signal is associated with fertility defects. We found that overexpression of PGR isoforms, PGR-A or PGR-B in the uterine epithelium resulted in severe subfertility due to failed embryo implantation in Wnt7acre/+ PGRALsL/+ (Wnt7aPRA) and Wnt7acre/+ PGRBLsL/+ (Wnt7aPRB) mice. Further studies indicated that decreased FOXO1 nuclear expression in the uterine epithelium during embryo implantation could be one of the major causes of failed embryo implantation in these mice. The major purpose of this study is to explore the mechanism of FOXO1 nuclear translocation in uterine luminal epithelium during embryo implantation. In the animal models it was observed that nuclear FOXO1 is strongly expressed in the luminal and granular epithelium in the Wnt7acre mouse uterus at pseudopregnant (D4.5). However, a much weaker and mainly cytoplasmic staining of FOXO1 can be observed in the uterine epithelium of the Wnt7aPRA and Wnt7aPRB mice. In the HEC1A cell line when treated with certain kinase inhibitors, a time dependent FOXO1 nuclear translocation can be observed at each inhibitor’s highest concentration. Future directions include testing kinase inhibitors and ROR2 activity in vivo.