# Biological mechanisms that eliminate aneuploid cells from a mosaic conceptus in the mouse model system

> **NIH NIH R01** · CALIFORNIA INSTITUTE OF TECHNOLOGY · 2024 · $513,655

## Abstract

Project Summary
 Many women struggle with infertility with only around 30% of pregnancies progressing to live birth and
the remainder failing through spontaneous abortions, the majority of which are associated with
aneuploidy. Here we use a mouse model for mosaic aneuploidy to study the effects of chromosome
mosaicism on development of the conceptus through the pre-, peri-and early post-implantation stages.
We have previously shown that aneuploidy results in two different responses in different adjacent tissues
of the pre-implantation embryo: cell cycle delay in the extra-embryonic trophectoderm that will establish
the placenta and apoptosis in the inner cell mass that will establish the foetus. We will now determine
the fate of the majority of aneuploid cells that persist into implantation stages and how, in many cases,
these can be eliminated without compromising implantation morphogenesis and the associated
transition in the state of pluripotency. We will determine the extent to which the embryo can compensate
for lost aneuploid cells to ensure development and determine the mechanisms employed by different
post-implantation tissues to cope with aneuploidy and protect the pluripotent lineage that generates all
germ layers and germline. As studies in diverse organisms indicate that global gene expression and
translation levels correlate with the degree of aneuploidy, we will determine whether aneuploidy in the
embryo results in proteomic imbalance leading to a common set of proteotoxic stress responses that
induce autophagy. We will elucidate the role of autophagy in the elimination of aneuploid cells from the
embryo and determine the roles of p53 and mTOR in this process. Our study will shed light onto
competition between aneuploid and diploid cells in development and will uncover new pathways that
regulate embryo growth and plasticity. It will inform IVF strategies in the clinic by building a working
knowledge of circumstances in which human embryos diagnosed as mosaic should or should not be
discarded. It will enable a more accurate assessment of the developmental potential of mosaic
aneuploid embryos and permit the development of better methods to assess the probability of successful
pregnancy.

## Key facts

- **NIH application ID:** 10778193
- **Project number:** 5R01HD101489-04
- **Recipient organization:** CALIFORNIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Magdalena Zernicka-Goetz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $513,655
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10778193

## Citation

> US National Institutes of Health, RePORTER application 10778193, Biological mechanisms that eliminate aneuploid cells from a mosaic conceptus in the mouse model system (5R01HD101489-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10778193. Licensed CC0.

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