Appropriate Crypt Formation in the Uterus for Embryo Homing and Implantation Requires Wnt5a-ROR Signaling
Jeeyeon Cha,
Amanda Bartos,
Craig Park,
Xiaofei Sun,
Yingju Li,
Sang-Wook Cha,
Rieko Ajima,
Hsin-Yi Henry Ho,
Terry P. Yamaguchi,
Sudhansu K. Dey
Affiliations
Jeeyeon Cha
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Amanda Bartos
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Craig Park
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Xiaofei Sun
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Yingju Li
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Sang-Wook Cha
Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Rieko Ajima
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA
Hsin-Yi Henry Ho
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Terry P. Yamaguchi
Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA
Sudhansu K. Dey
Division of Reproductive Sciences, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
Embryo homing and implantation occur within a crypt (implantation chamber) at the antimesometrial (AM) pole along the uterus. The mechanism by which this is achieved is not known. Here, we show that villi-like epithelial projections from the main uterine lumen toward the AM pole at regularly spaced intervals that form crypts for embryo implantation were disrupted in mice with uterine loss or gain of function of Wnt5a, or loss of function of both Ror1 and Ror2. This disruption of Wnt5a-ROR signaling resulted in disorderly epithelial projections, crypt formation, embryo spacing, and impaired implantation. These early disturbances under abnormal Wnt5a-ROR signaling were reflected in adverse late pregnancy events, including defective decidualization and placentation, ultimately leading to compromised pregnancy outcomes. This study presents deeper insight regarding the formation of organized epithelial projections for crypt formation and embryo implantation for pregnancy success.
