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4 October 2017 Porcupine-dependent wnt activity within the uterine epithelium is essential for fertility
Omar Farah, Steffen Biechele, Janet Rossant, Daniel Dufort
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Abstract

The secretion of mammalian Wnt ligands within the cell is dependent on the activity of Porcupine, a gene located on the X-chromosome that encodes for a membrane-bound O-acyl transferase. Here, we report that postnatal ablation of Porcupine in the uterine luminal epithelium alone results in the decrease in endometrial gland number. Despite having uterine glands, mutant females are completely infertile. Epithelial ablation of Porcupine causes defects in timely apposition of the lumen, along with failure to respond to artificial decidual induction. Interestingly, progesterone supplementation was able to rescue the initiation of decidualization, but the decidua was not maintained and subsequently resorbed. Transcriptome analysis demonstrated that deletion of Porcupine in the epithelium resulted in the stromal dysregulation of members of the Wnt signaling pathway (Lef1, Wnt4, and Wnt16), dysregulation of receptors and ligands in the Notch signaling pathway (Notch1, Notch4, and Dll4) as well as Hoxa10. Our results demonstrate the crucial requirement of Wnt signaling in the epithelium for fertility and demonstrate that epithelial Wnts regulate stromal Wnt gene expression as well as regulating the expression of essential signaling factors and effectors required for successful embryo implantation.

Summary Sentence

Epithelial Porcupine is important for pregnancy.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Omar Farah, Steffen Biechele, Janet Rossant, and Daniel Dufort "Porcupine-dependent wnt activity within the uterine epithelium is essential for fertility," Biology of Reproduction 97(5), 688-697, (4 October 2017). https://doi.org/10.1093/biolre/iox119
Received: 29 April 2017; Accepted: 27 September 2017; Published: 4 October 2017
JOURNAL ARTICLE
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KEYWORDS
decidualization
glands
luminal closure
porcupine
uterus
WNT
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