# Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic health

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $461,253

## Abstract

Abstract
Global challenges to human health include a well-documented decline in human fertility and a dramatic increase
in the prevalence of obesity related metabolic disorders. There is now compelling evidence that these health
challenges are associated with environmental chemicals that can influence endocrine activity. However, this
premise has evolved from studies with acute single chemical exposures in altricial, genetically restricted, animal
models. The proposed study will address the central hypothesis that exposure to a real-life mixture of
environmental chemicals, prior to and throughout pregnancy, results in transgenerational epigenetic effects in
offspring that affect metabolism and reproduction. The proposal will use a unique, real-life chemical exposure
and a translationally relevant animal model whereby sheep are exposed to biosolids. Humans are exposed to a
wide mixture of environmental chemicals, at typically low concentrations, throughout their lifespan. Grazing
pregnant sheep on pastures treated with biosolids generated from human sewage provides a precocial model
with a developmental trajectory similar to humans. This provides a novel approach to examine the effects of
environmental chemical mixtures to which we are all exposed. The specific aims are: (1) to characterise lifetime
changes in metabolic function of male and female offspring spanning three generations (i.e. F1, F2 and F3)
following F0 exposure to biosolids treated pasture; (2) to assess changes in reproductive potential of male and
female offspring across three generations (i.e. F1, F2 and F3) following F0 exposure to biosolids pasture; (3) to
determine epigenetic changes, and their functional relationships, to transcriptional networks governing
transgenerational effects of maternal biosolids exposure on offspring metabolism and fertility. This
comprehensive analysis will provide proof-of-concept data on the effects of real-life chemical exposure in a
relevant experimental paradigm. This will significantly enhance our ability to predict and inform policy
development with the aim of ameliorating detrimental effects of environmental-chemical exposure and to improve
metabolic and reproductive health.

## Key facts

- **NIH application ID:** 10102250
- **Project number:** 5R01ES030374-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Neil Price Evans
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $461,253
- **Award type:** 5
- **Project period:** 2020-02-10 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102250

## Citation

> US National Institutes of Health, RePORTER application 10102250, Transgenerational consequences of pre-conceptional and in utero exposure to real-life chemical mixtures on fertility and metabolic health (5R01ES030374-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102250. Licensed CC0.

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