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Cell Rep. 2014 Jul 24;8(2):382-92. doi: 10.1016/j.celrep.2014.06.027. Epub 2014 Jul 17.

Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling.

Author information

  • 1Division 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.
  • 2Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • 3Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
  • 4Cancer 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.
  • 5Department 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.
  • 6Cancer and Developmental Biology Laboratory, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD 21702, USA.
  • 7Division 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.

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.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PMID:
25043182
[PubMed - indexed for MEDLINE]
PMCID:
PMC4120233
Free PMC Article
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