# Glucocorticoid Signaling and Stress in the Developing Mammalian Germline

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $27,280

## Abstract

PROJECT SUMMARY / ABSTRACT
The consequences of stress on organs such as the heart and immune system are well established, but it is only
recently shown in mice that stress experienced during pregnancy can cause molecular and behavioral changes
in the exposed fetus and even their offspring. The transmission of such phenotypes across generations implies
that germ cells sense and maintain epigenetic memories of stress experienced in the womb; how the primordial
germ cells (PGCs) within the developing embryo detect and respond to these stress signals is unknown. The
major circulating hormone released in response to stress is cortisol, which is the ligand for glucocorticoid receptor
(GR). GR induces highly cell type-specific transcriptional changes in many cell types, however its function in
PGCs has yet to be explored. My preliminary studies show robust expression and dynamic localization of GR in
fetal germ cells that suggests its activity. PGCs naturally undergo genome-wide epigenetic reprogramming to
remove somatic and parental imprints, which leads to the de-repression of transposable elements (TE) that are
normally silenced by methylation at their promoters. If not properly re-silenced, TEs will generate large numbers
of DNA double strand breaks during transposition, posing a serious risk to germline integrity. Across many
organisms, stress can induce low level expression of TEs and transposition, which can transport gene regulatory
elements to new genomic loci, altering neighboring gene expression to aid in cellular stress adaptation and
survival. While this beneficial role for stress-induced TE expression has been shown in other eukaryotic systems,
it is unclear whether this also occurs in mammalian germ cells. We hypothesize that stress-mediated changes
in TE expression could have profound effects on proper PGC development and subsequent fertility. This
proposal aims to characterize the GR-mediated stress response within developing PGCs, as well as its impact
on TE expression and subsequent influence on germline integrity. We will use a combination of genetic mouse
models, high throughput sequencing-based genomic approaches, as well as various ex vivo models of stress.
The results from this proposal will provide insight into the relationship between stress and the mammalian
germline, and will therefore help us to better understand and prevent stress-induced disorders in future
generations.

## Key facts

- **NIH application ID:** 10231082
- **Project number:** 5F31HD101234-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Steven Anthony Cincotta
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $27,280
- **Award type:** 5
- **Project period:** 2020-08-01 → 2022-06-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10231082

## Citation

> US National Institutes of Health, RePORTER application 10231082, Glucocorticoid Signaling and Stress in the Developing Mammalian Germline (5F31HD101234-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10231082. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*