title: Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling.
abstract: 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.
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Jeeyeon
authors.initials: J
authors.lastname: Cha
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bartos
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Park
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Yingju
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Cha
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA; Division of Mammalian Development, National Institute of Genetics, Yata 1111, Mishima 411-8540, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Davis, CA 95616, USA.
authors.forename: Hsin-Yi Henry
authors.initials: HY
authors.lastname: Ho
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: sk.dey@cchmc.org.
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
mesh_terms: D000818:Animals; D003656:Decidua / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010064:Embryo Implantation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D051379:Mice; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477011:Ror1 protein, mouse; C477010:Ror2 protein, mouse