H2020Individual fellowship2022–2024

IMPLANTATION · A stem cell-based approach for modelling implantation in vitro

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2022-09-01 → 2024-08-31
EU contribution
€174,167
Participants
1
Scheme
MSCA-IF

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Results in brief

A stem cell-based approach for modelling implantation in vitro

This research investigates the early stages of human embryo development and implantation, focusing on developing realistic stem cell-based models of human blastocyst. Human embryo implantation remains challenging to study due to the embryo's small size and the inaccessibility of implantation processes within the womb. By developing “human blastoids” from stem cells, we can now replicate key early stages of embryo development and implantation in a dish, enabling detailed exploration of this complex biological process. Understanding implantation is essential for improving reproductive health. This knowledge can directly enhance infertility treatments, particularly in optimizing in vitro fertilization (IVF) procedures, giving greater hope to couples facing fertility challenges. Moreover, these insights can guide the development of new contraceptive options and may even contribute to reducing the risk of chronic conditions linked to reproductive health. The main objectives of this project were to establish a reliable, scalable model for studying human embryo implantation and to identify molecular mechanisms, like the mTOR signaling pathway, that influence embryo development timing and attachment. This work has led to the discovery that inhibiting mTOR activity can put human cells in a dormant state, slowing their development—a feature seen in some animals but now observed in human cells. The blastoid model enables new ways to study implantation and supports further investigation into reproductive biology. Ultimately, these findings have broad implications for fertility treatments, contraceptive development, and the future of reproductive health.

Data: CORDIS, © European Union

Project objective

The first physical contact between the embryo and the uterus is a complex and timely coordinated process, which is crucial for positive pregnancy outcome. During that process of implantation, the embryo attaches and invades to nest into the uterus. Managing embryo implantation has wide implications for public health, including treating infertility (e.g., improving IVF outcomes) and for family planning (improving contraception). However, the tiny size of the embryo and inaccessibility into the womb make implantation a true black box in developmental biology. Three technological breakthroughs, i.e., single cell sequencing, endometrial organoids and blastoid technologies, now made it possible to deeply and finely investigate implantation. Here, I aim at leveraging these technologies to create a stem cell-based platform to model the blastocyst-uterus interaction and to reveal molecular mechanisms mediating implantation. This platform will be amenable to high-throughput screening, gene editing, and live imaging, to identify the molecular regulators of implantation. If successful, this study will provide a biologically relevant, easily accessible and experimentally amenable system to perform in-depth studies with scientific and clinical impacts to understand and potentially treat conditions such as infertility, reproductive decline, develop novel contraceptive and in the long term, to develop drugs to improve reproductive health and prevent several chronic diseases.

Original text from CORDIS.

Participants

  • INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH · WienCoordinatorAustria

Links

Data: CORDIS, © European Union