# Determining the role of sperm microRNAs in early development and non-genetic inheritance

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2024 · $48,974

## Abstract

ABSTRACT
Historically, sperm were largely disregarded as contributors of non-genetic information due to their significantly
reduced cytoplasmic contribution to the zygote relative to eggs. However, recent studies have demonstrated
that sperm can transmit non-genetic information to offspring, thereby modulating inherited phenotypes.
Specifically, the microRNA (miRNA) content of sperm is altered by changes to paternal diet and exposure to
stress and various toxins. While several studies have causally demonstrated that the microinjection of specific
sperm miRNAs can induce changes in offspring phenotypes, the molecular mechanism of action of sperm
miRNAs in early development remains unknown. The primary functions of miRNAs are to downregulate
messenger RNA (mRNA) transcripts via destabilization, decay, and translational repression. My preliminary
data shows that a single miRNA has the ability to downregulate dozens of mRNA transcripts during early
embryonic development. I hypothesize that sperm miRNAs play an important role in modulating early
development by altering embryonic gene expression via the contribution of double-stranded miRNAs to the
zygote during fertilization. To test this hypothesis, I will determine the effects of sperm miRNAs on early
development by injecting miRNAs into mouse eggs chemically induced to develop in the absence of sperm
(parthenotes). This system will allow me to study how a single component of sperm, miRNAs, mechanistically
function during early embryonic development in the absence of all other contents of sperm. I will microinject
parthenotes with individual sperm miRNAs upregulated upon stress exposure (Aim 1a) and important for
embryonic development (Aim 1a) and quantitate the transcriptome throughout early development using single-
embryo RNA-sequencing (RNA-seq) to determine how miRNAs regulate embryonic gene expression. In Aim
2a, I will selectively digest either single- or double-stranded sperm miRNAs to systematically analyze which
sperm miRNAs are delivered to zygotes as duplexes using small RNA-seq. In Aim 2b, I will use small RNA-
seq to probe whether sperm acquire precursor miRNAs during maturation. Duplex molecules will have
increased stability and enhanced functionality to regulate embryonic gene expression due to their increased
efficiency of loading into AGO. Together, my project will provide novel insight into the functions of sperm
miRNAs by providing a comprehensive and mechanistic understanding of how they regulate early embryonic
development.

## Key facts

- **NIH application ID:** 10996310
- **Project number:** 1F31HD114433-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Grace Suneuy Lee
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996310

## Citation

> US National Institutes of Health, RePORTER application 10996310, Determining the role of sperm microRNAs in early development and non-genetic inheritance (1F31HD114433-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10996310. Licensed CC0.

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