# Placental models to support embryogenesis in vitro

> **NIH NIH DP1** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2024 · $1,165,500

## Abstract

Most human pregnancies fail around the time of embryo implantation. Yet, the developmental mechanisms
of this stage and how they go awry remain a mystery, because the implanted embryo is inaccessible to
analysis within the body of the mother. Uncovering these mechanisms is of critical importance to overcome
existing barriers to fertility and proper development. We have successfully generated systems that enable
development of natural mouse and human embryos from pre- to post-implantation stages in vitro, and built
stem cell-derived synthetic mouse embryos that can mimic some aspects of early post-implantation
development. But approaches to study development continuously through the implantation stage and
beyond gastrulation are lacking. We now propose to create a maternal-like environment that permits the
long-term survival of both natural and synthetic mouse embryos. Our first challenge will be to engineer
synthetic pre-implantation blastocysts with an expanded ability to generate the full range of correctly
functioning extra-embryonic tissues. This breakthrough is expected to enable their implantation and
development in utero, and may eventually transform approaches for engineering genetically modified mice.
We will use these new tools to determine the precise cellular and molecular mechanisms that allow synthetic
blastocysts to interact with the uterus in foster mothers. Our second challenge will be to generate artificial
substrates, comprising hydrogels and proteins of the decidual extra-cellular matrix, to facilitate implantation
events. In parallel, we will engineer synthetic placental-like structures for natural and synthetic embryo
development using organoids derived from trophoblast and endometrial tissue. These systems would allow
investigations and tracking of how insults to pre- and peri-implantation development, such as the exposure
to pathogens, toxins, or teratogens affect subsequent development and life. Our third challenge will be to
utilize these systems to discover the molecular events that accompany implantation. We will take advantage
of our in vitro placental systems to investigate the chemical and physical signalling events that are key for
development and determine how improved extra-embryonic contributions affect embryonic development
until neurulation. These innovations will allow us to finally decipher a stage of development that is currently
out of reach and of which our knowledge is greatly lacking. This will bring insight into a time of development
when most pregnancies fail and thereby lead to advances in assisted reproductive technology; it will offer
new screening routes for drug testing and environmental safety; and it will advance our knowledge of the
use of stem cells in organogenesis and regenerative medicine.

## Key facts

- **NIH application ID:** 10881737
- **Project number:** 5DP1HD104575-05
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Magdalena Zernicka-Goetz
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,165,500
- **Award type:** 5
- **Project period:** 2020-09-30 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881737

## Citation

> US National Institutes of Health, RePORTER application 10881737, Placental models to support embryogenesis in vitro (5DP1HD104575-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10881737. Licensed CC0.

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