Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation

Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo–uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudi...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 113; no. 50; pp. E8079 - E8088
Main Authors Yuan, Jia, Cha, Jeeyeon, Deng, Wenbo, Bartos, Amanda, Sun, Xiaofei, Ho, Hsin-Yi Henry, Borg, Jean-Paul, Yamaguchi, Terry P., Yang, Yingzi, Dey, Sudhansu K.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 13.12.2016
SeriesPNAS Plus
Subjects
Biological Sciences
Blood vessels
Embryos
Morphology
PNAS Plus
Pregnancy
Proteins
Reproductive system
Transplants & implants
Vangl2
uterus
PCP
crypt
embryo implantation
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Summary:Blastocyst implantation is a complex process requiring coordination of a dynamic sequence of embryo–uterine interactions. Blood vessels enter the uterus from the mesometrium, demarcating the uterus into mesometrial (M) and antimesometrial (AM) domains. Implantation occurs along the uterine longitudinal axis within specialized implantation chambers (crypts) that originate within the evaginations directed from the primary lumen toward the AM domain. The morphological orientation of crypts in rodent uteri was recognized more than a century ago, but the mechanism remained unknown. Here we provide evidence that planar cell polarity (PCP) signaling orchestrates directed epithelial evaginations to form crypts for implantation in mice. Uterine deletion of Vang-like protein 2, but not Vang-like protein 1, conferred aberrant PCP signaling, misdirected epithelial evaginations, defective crypt formation, and blastocyst attachment, leading to severely compromised pregnancy outcomes. The study reveals a previously unrecognized role for PCP in executing spatial cues for crypt formation and implantation. Because PCP is an evolutionarily conserved phenomenon, our study is likely to inspire implantation studies of this signaling pathway in humans and other species.
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Edited by R. Michael Roberts, University of Missouri-Columbia, Columbia, MO, and approved November 4, 2016 (received for review September 7, 2016)
2Present address: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
1J.Y. and J.C. contributed equally to this work.
Author contributions: J.Y., J.C., W.D., H.-Y.H.H., J.-P.B., and S.K.D. designed research; J.Y., J.C., W.D., A.B., X.S., and S.K.D. performed research; J.-P.B., T.P.Y., Y.Y., and S.K.D. contributed new reagents/analytic tools; J.Y., J.C., W.D., A.B., X.S., H.-Y.H.H., J.-P.B., T.P.Y., Y.Y., and S.K.D. analyzed data; and J.Y., J.C., H.-Y.H.H., and S.K.D. wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1614946113