# Center for Male Reproductive Epigenomics

> **NIH NIH P50** · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · 2022 · $1,452,333

## Abstract

Project Summary
We propose to establish a “Center for Male Reproductive Epigenomics” (herein called the “Center”) in
response to the NICHD RFA-HD-19-017. The Center aims to study three key aspects of intergenerational
epigenetic inheritance of environmentally-induced epimutations: 1) the impact of lifestyle (diet/activity) on
the integrity of the sperm epigenome, 2) the molecular mechanisms underlying transmission of lifestyle-
induced sperm epimutations to offspring, and 3) the mechanisms by which inherited epimutations can
predispose disease states in offspring. By studying the sperm epigenome of male mice maintained on
either a high fat diet without exercise or a normal diet + exercise, or transitioned from the former to the
latter, in parallel with that of obese, inactive men maintaining an unhealthy lifestyle or transitioned to a
healthy diet + exercise lifestyle, we will test our central hypothesis, i.e., paternal epigenetic inheritance of
lifestyle-induced metabolic disorders is achieved through a combinatorial molecular mechanism involving
sncRNAs, DNA methylation and histone modifications, which relay epimutations from somatic cells to
sperm and from a father’s sperm to his offspring where they predispose development of disease-related
traits. Our studies in men (Project 1) will establish the extent of the deleterious effects of an unhealthy
lifestyle (high fat/caloric diet and physical inactivity) on the human sperm epigenome and will determine
whether the incidence of these epimutations can be reduced if an obese/inactive man adopts a healthy
lifestyle (low fat/caloric diet + exercise). Our studies in mice (Projects 2 and 3) will reveal the mechanisms
by which an unhealthy lifestyle leads to formation of epimutations in spermatozoa that are subsequently
transmitted to, propagated within, and deleterious to male offspring – based on mechanistic studies that
cannot be done in men. In the short term, our studies will elucidate the underlying mechanisms by which
an unhealthy lifestyle in men can predispose development of unhealthy phenotypes or disease in their
offspring and the extent to which transition from an obese/inactive lifestyle to a healthy diet + exercise
lifestyle can mitigate these effects. In the long term, a thorough understanding of how lifestyle-induced
epimutations initially occur and are transmitted from a father to his sons (= intergenerational epigenetic
inheritance) will form the basis for future investigations into mechanisms underlying the subsequent
transmission of lifestyle-induced epimutations to multiple subsequent generations (= transgenerational
epigenetic inheritance).

## Key facts

- **NIH application ID:** 10260432
- **Project number:** 5P50HD098593-03
- **Recipient organization:** LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
- **Principal Investigator:** Wei Yan
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,452,333
- **Award type:** 5
- **Project period:** 2019-09-13 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10260432

## Citation

> US National Institutes of Health, RePORTER application 10260432, Center for Male Reproductive Epigenomics (5P50HD098593-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10260432. Licensed CC0.

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