# Post-Transcriptional Regulation of Embryo Implantation

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $406,587

## Abstract

PROJECT SUMMARY
Successful establishment of pregnancy requires the uterus to undergo several well-timed cellular changes to
allow the embryo to implant. Thus, even when the blastocyst develops normally, impaired uterine function can
lead to implantation failure or early embryo miscarriage. The uterine endometrium prepares for implantation in
two steps. First, the endometrial epithelium proliferates, loses polarity, and differentiates, allowing the embryo
to attach. Second, the underlying stromal cells proliferate and differentiate into decidual cells, allowing the
embryo to implant. These two processes are coordinated by cell-type specific responses to the steroid
hormones estrogen and progesterone. However, we lack a complete picture of the downstream responses to
these hormones, hampering our ability to develop new strategies to prevent early pregnancy loss. To address
this knowledge gap, this proposal focuses on a new area in endometrial physiology, alternative mRNA splicing.
Specifically, this proposal will test the central hypothesis that the splicing factor SF3B1 mediates progesterone-
driven alternative splicing that is essential for uterine receptivity and decidualization. This idea is founded on
the following pieces of preliminary data. First, a high-throughput siRNA screen revealed that SF3B1 was
required for human endometrial stromal cell decidualization. Second, knock down of SF3B1 impaired in vitro
decidualization more than knock down of eight other splicing factors. Third, treatment with the SF3B1-specific
inhibitor Pladienolide B inhibited human endometrial stromal cell decidualization in vitro and murine
endometrial decidualization in vivo. Fourth, treatment with Pladienolide B impaired embryo implantation and
decidualization in mice. Fifth, SF3B1 protein is elevated in endometrial stromal cells during peri-implantation in
mice. Finally, SF3B1 protein but not mRNA in stromal cells was elevated during artificial decidualization in
mice, and progesterone stabilized SF3B1 protein but not mRNA in primary human endometrial stromal cells.
The work proposed here will build on these strong preliminary data and test the hypothesis by pursuing the
following specific aims: (Aim 1) Define the functions of SF3B1 in uterine receptivity and decidualization; (Aim 2)
Identify progesterone-induced, SF3B1-dependent alternative splice variants in the endometrium; (Aim 3)
Determine the mechanism by which progesterone regulates SF3B1. At the level of basic science, this project
will identify the mechanisms that underlie SF3B1-driven mRNA splicing, which is crucial for progesterone-
driven endometrial decidualization. Of translational significance, this work will identify novel transcript variants
that may contribute to recurrent pregnancy loss. In the long term, such knowledge can be used to develop new
strategies to diagnose or prevent early pregnancy loss. Together, this work will help advance Theme 2 of the
NICHD 2020 Strategic Plan, which aims to "...

## Key facts

- **NIH application ID:** 10367681
- **Project number:** 1R01HD104813-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ramakrishna Kommagani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $406,587
- **Award type:** 1
- **Project period:** 2022-08-11 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367681

## Citation

> US National Institutes of Health, RePORTER application 10367681, Post-Transcriptional Regulation of Embryo Implantation (1R01HD104813-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10367681. Licensed CC0.

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