# Molecular signaling in uterine receptivity to implantation

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $381,333

## Abstract

Summary
Human reproduction is complex and fairly inefficient. More than 30% of conceptions
result in spontaneous abortion with most losses occurring around the time of
implantation. These unwanted pregnancy losses contribute to major psychological,
economical, and clinical conflicts. Inadequate uterine milieu is one cause for this
failure—to explore deeper into the mechanics of successful pregnancy, we recognize
that effective two-way interactions between a competent blastocyst and the receptive
uterus are a prerequisite for implantation in placental mammals including humans. The
blastocyst will implant only when this molecular dialogue is established. Normally,
implantation in mice occurs within a specialized implantation chamber (crypt) formed by
luminal epithelial (LE) evaginations towards the antimesometrial (AM) side of the uterus.
The underlying mechanism by which evenly spaced crypts are formed towards the AM
pole remains elusive. Our recent work in mice shows that regulated Wnt5a-ROR
signaling is critical to implantation and pregnancy establishment. We propose that this
signaling is mediated by planar cell polarity (PCP) by engaging PCP components
Vangl2, Scribble, Celsr1 and Dvl2. We will test the hypothesis that PCP activity in
collaboration with non-canonical Wnt5a-ROR signaling directs crypt formation and
implantation. Aim 1 will test if major PCP signaling constituents are active in the uterus
around the time of implantation. Aim 2 will investigate whether uterine PCP activity is
critical for crypt formation for implantation through the use of genetic mouse models. Our
preliminary results in mice with uterine deletion of Vangl2 (a core component in PCP
signaling) show defective implantation and compromised pregnancy outcomes. These
results have created a unique window of opportunity to generate molecular and genetic
information on a potential mechanism by which the uterine environment becomes
conducive to blastocyst homing in the crypt for implantation and pregnancy
establishment. The genetic mouse models provide mechanistic information relevant to
female fertility which is not feasible to perform in humans. There is a strong possibility
that PCP signaling plays a major role in human implantation, since the human proteome
atlas has documented the expression of Vangl2, Vangl1 and Wnt5a in the human uterus.
Thus, it is prudent to gather mechanistic and genetic evidence regarding PCP’s
requirement in implantation in mouse models to better understand human implantation.

## Key facts

- **NIH application ID:** 9975008
- **Project number:** 5R01HD068524-10
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Sudhansu K Dey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,333
- **Award type:** 5
- **Project period:** 2011-09-26 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975008

## Citation

> US National Institutes of Health, RePORTER application 9975008, Molecular signaling in uterine receptivity to implantation (5R01HD068524-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9975008. Licensed CC0.

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