# Heritable epigenetic mechanisms of paternal THC exposure

> **NIH NIH F32** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $15,040

## Abstract

PROJECT SUMMARY
There is a growing appreciation that a father’s preconception stress, diet, or drug use can directly affect the
development of his children via epigenetic mechanisms in the germline. Accordingly, recent findings from our
lab revealed that parental (mother and father) exposure to 9-tetrahydrocannabinol (THC) increased drug-
seeking behavior in male offspring. Suggesting a significant role for the father, I found that THC significantly
alters an epigenetic mechanism in sperm known to play a causal role in heritable neurobehavioral phenotypes.
Given the progressive legalization of recreational cannabis use, it is imperative that the associated
reproductive and intergenerational health risks become better defined. Therefore, I will examine the heritable
epigenetic effects of paternal THC exposure on the sperm, developing embryo, and fetal brain.
In Aim 1, I will examine the effects of THC on sperm small noncoding RNAs across three translationally-
relevant doses. Subsequently, in Aim 2a, I will characterize the effects of paternal THC exposure on gene
expression in the early embryo. Moreover, Aim 2b will follow-up on preliminary experiments showing that a low
dose THC exposure reduces sperm-borne microRNA-34c by examining the effects of microRNA-34c inhibition
on early embryonic gene expression programming. Finally, in Aim 3, I will determine the heritable epigenetic
effects of paternal THC exposure on prenatal neurodevelopment by examining genome-wide chromatin
accessibility in embryonic striatal neurons.
This project represents an important advancement in our understanding of the intergenerational effects of THC
exposure, aiming to identify novel mechanisms of epigenetic inheritance through the male germline. The
findings will help determine potential health risks associated with the cannabis use of fathers-to-be.

## Key facts

- **NIH application ID:** 10129190
- **Project number:** 5F32DA050403-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gregory Ronald Rompala
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $15,040
- **Award type:** 5
- **Project period:** 2020-02-07 → 2021-04-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129190

## Citation

> US National Institutes of Health, RePORTER application 10129190, Heritable epigenetic mechanisms of paternal THC exposure (5F32DA050403-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129190. Licensed CC0.

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