# Preconceptual paternal environmental allergen exposure, sperm epigenetics and offspring asthma development

> **NIH NIH R21** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $238,500

## Abstract

The “Developmental Origin of Health and Disease” (DOHaD) hypothesis posits that early life exposures
(nutritional, environmental, inflammatory) influence offspring susceptibility to a number of non-communicable
diseases. Allergic asthma, a disease that affects over 300 million people worldwide, is continuing to increase in
prevalence. Consistent with the DoHAD hypothesis, there is growing evidence that maternal, and paternal
exposures can influence both risk and severity of disease in offspring. Mechanisms involved have been
described for maternal exposure-driven modulation of asthma development, where immune or environmental-
derived factors can influence the epigenome of the oocyte or developing fetus. In contrast, while influences of
specific paternal exposures (tobacco smoke, specific occupations) have been described in humans, mechanisms
involved are unclear. Our novel preliminary data demonstrate that paternal HDM exposure to the environmental
allergen house dust mite (HDM) is associated with a reduced asthma severity, and increased recruitment of
unique pulmonary T cell populations in offspring. While paternal exposures have been demonstrated to influence
offspring behavior, and/or development of metabolic dysfunction, these innovative preliminary data are the first
to demonstrate that paternal environmental exposures to environmental stimulants can influence development
of chronic inflammatory diseases in offspring. As epigenetic modifications or alterations in the small RNA species
present in sperm were found to be causative factors in models of inheritance of acquired behavioral or metabolic
dysfunction, we hypothesize that environmental antigen exposure induces epigenetic modifications in DNA
methylation or types of small RNA species present in sperm, and that these changes reduce offspring asthma
severity in a germ cell-dependent manner. This innovative hypothesis will be tested in two independent, yet
related specific aims. Specific Aim 1: To identify sperm epigenetic differences associated with paternal
environmental allergen exposure. Using sperm from control, or environmental antigen-exposed male mice we
will quantify differences in small RNA species and DNA methylation patterns (DMRs) present in sperm of
environmental-allergen exposed males utilizing well established pipelines. Specific Aim 2: To test the
hypothesis that paternal environmental allergen exposure influences offspring asthma via germ-cell
intrinsic mechanisms. In vitro fertilization (IVF)-derived embryos derived from control, or environmental
allergen-exposed fathers, will be implanted into pseudopregnant females mated with vasectomized control,
and/or environmental allergen-exposed males. The asthma phenotype will be assessed in all offspring. A better
comprehension of the mechanisms through which paternal exposures can influence offspring immunity will have
broad reaching implications for public health and increase our understanding of factors that can influence t...

## Key facts

- **NIH application ID:** 10122903
- **Project number:** 5R21AI152100-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Ian Paul Lewkowich
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $238,500
- **Award type:** 5
- **Project period:** 2020-03-06 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122903

## Citation

> US National Institutes of Health, RePORTER application 10122903, Preconceptual paternal environmental allergen exposure, sperm epigenetics and offspring asthma development (5R21AI152100-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10122903. Licensed CC0.

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