# Dietary effects on the sperm epigenome

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2021 · $655,518

## Abstract

Project Summary/Abstract
Although inheritance of DNA sequence underpins the majority of heritability in
biology, it is increasingly clear that information beyond the genome – known as
epigenetic information – is also transmitted to the next generation, with vast
implications for health and development. Over the past decade, we have
developed several paternal-effect paradigms in mice to address how epigenetic
information in gametes affects the phenotype of offspring, and whether an
animal's environmental conditions can affect heritable epigenetic information,
thereby “reprogramming” the offspring's phenotype. We discovered that paternal
environmental exposures can reproducibly alter offspring physiology, and we are
uncovering molecular mechanisms underlying this information transfer, focusing
on the largely unexplored role for sperm RNAs in control of early mammalian
development.
 Small RNAs play central roles in well-characterized transgenerational
epigenetic inheritance paradigms such as paramutation in maize and RNA
interference in C. elegans, and it is increasingly clear that small RNAs in
mammalian sperm play key functional roles in the early embryo. Not only is the
overall sperm small RNA payload essential for early development, but the levels
of many specific small RNAs in sperm have been shown to change in response
to paternal environmental conditions. These early and exciting studies motivate a
more thorough characterization of the role of small RNAs in mammalian
development.
 Here, we propose to take a three part approach to the regulation and
function of sperm small RNAs in preimplantation embryos. In the first part, we
propose to systematically characterize the functions of sperm RNAs in the early
embryo, manipulating small RNA levels in zygotes and measuring resulting
regulatory consequences by single-embryo RNA-Seq. Next, we plan to survey
the landscape of environmental effects on sperm RNAs, establishing most of the
credible paternal effect paradigms under the same conditions and measuring
sperm RNA levels and resulting early embryonic regulatory consequences in
response to these environmental perturbations. Finally, we seek to uncover the
mechanisms underlying the functions of 5' tRNA fragments, an understudied
class of regulatory molecules which comprise the dominant small RNA species
carried by mature mammalian sperm.
 Together, these studies will provide unprecedented insights into the
regulation of small RNA levels in mammalian sperm, and their functions in the
preimplantation embryo. These systematic analyses of epigenetic signals in
sperm will not only reveal new principles of biological inheritance, but will also
enable us to predict and potentially manipulate offspring phenotypes in ways that
promote health.

## Key facts

- **NIH application ID:** 10141277
- **Project number:** 5R01HD080224-08
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** OLIVER J RANDO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $655,518
- **Award type:** 5
- **Project period:** 2014-04-14 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141277

## Citation

> US National Institutes of Health, RePORTER application 10141277, Dietary effects on the sperm epigenome (5R01HD080224-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10141277. Licensed CC0.

---

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