# Investigating the Developmental Mechanisms of TCDD-Induced Reproductive Dysregulation

> **NIH NIH F31** · WAYNE STATE UNIVERSITY · 2021 · $43,636

## Abstract

PROJECT SUMMARY:
Environmental exposure to endocrine-disrupting chemicals is heavily implicated in the increasing incidence of
infertility and adverse reproductive outcomes across industrialized countries. As early critical periods are highly
susceptible to endocrine system disruption, even very low-doses of these chemicals can shift developmental
trajectories, leading to lifelong and/or multigenerational disease consequences. Therefore, the long-term goal
of our work is to investigate both the specific genetic and epigenetic mechanisms through which toxicant
exposures induce later-life reproductive effects and the windows during which this disruption occurs, in order to
inform the development of clinical and therapeutic interventions.
To address this goal, our lab has previously used zebrafish (Danio rerio), an NIH-validated model organism
allowing easy developmental access to toxicological endpoints, to study the effects of early toxicant exposures
on adult disease outcomes. Findings of skewed sex ratios and male-mediated transgenerational infertility
guided us to further discover specific histologic and transcriptomic changes in the testes of adult male fish, all
of which were heavily implicated in infertility. These outcomes told a compelling story of genetic and epigenetic
changes in reproductive tissues persisting across the lifespan and inherited to the unexposed F2 generation.
However, as everything to this point was assessed in adults, the developmental mechanisms behind these
outcomes remain to be determined. The aims of this project propose, initially, the creation of a sex-specific
transgenic fish line using well-established methods, in order to gain early developmental access to
reproductive tissues and track their development over time. Creation of this line will not only be invaluable to
this project, but will also provide a beneficial tool widely applicable to the field of developmental and
reproductive toxicology. Using this line, the remaining aims propose to use a variety of physiological,
behavioral, genetic, and epigenetic techniques to longitudinally investigate the developmental mechanisms of
toxicant-induced infertility. This work promises to provide novel insights into pathways of reproductive
development, closely linking adult and multigenerational disease with corresponding developmental origins.

## Key facts

- **NIH application ID:** 10063524
- **Project number:** 5F31ES030278-03
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Danielle Meyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $43,636
- **Award type:** 5
- **Project period:** 2018-12-15 → 2021-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063524

## Citation

> US National Institutes of Health, RePORTER application 10063524, Investigating the Developmental Mechanisms of TCDD-Induced Reproductive Dysregulation (5F31ES030278-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10063524. Licensed CC0.

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