# Examining the role of immune activation in transposon-triggered sterility.

> **NIH NIH F31** · DUKE UNIVERSITY · 2024 · $41,910

## Abstract

ABSTRACT.
Infertility is a problem that affects one out of five couples, yet the cause of sterility is unknown in 30% of cases.
One threat to viable gamete development is activity of a subset of transposons known as endogenous
retroviruses (ERVs). ERVs have the ability to self-replicate and sometimes mobilize, creating new genomic
insertions within the same cell or even neighboring cells. Previous studies have demonstrated that, in
Drosophila, ERV activation within the follicle cells of developing eggs causes sterility. The current explanation
for ERV-triggered sterility postulates that ERVs migrate from the follicle cells into the oocyte and insert
themselves into new genomic loci, damaging DNA integrity. However, our lab has found no evidence of novel
ERV insertions being made into the oocyte genome, suggesting sterility may arise from uncharacterized
mechanism(s). Here, we propose an alternative explanation for transposon-triggered sterility: we hypothesize
that ERV derepression induces sterility through activation of an aberrant immune response. We found that
depletion of key immune pathway components rescued fertility despite ERV hyperactivity. These data provide
evidence that transposon-triggered sterility may be due to immune activation rather than DNA damage within
the oocyte. This proposal seeks to investigate how the immune system recognizes ERVs and whether that
immune response can cause sterility. Ultimately, these findings may provide an alternative explanation for
ERV-triggered sterility as well as advance our understanding of how ERVs impact human health.

## Key facts

- **NIH application ID:** 10917116
- **Project number:** 5F31HD113207-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Kara Michelle Stark
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,910
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917116

## Citation

> US National Institutes of Health, RePORTER application 10917116, Examining the role of immune activation in transposon-triggered sterility. (5F31HD113207-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10917116. Licensed CC0.

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