# Long-term effects of developmental exposure to a mixture of thyroid disruptors associated with hydrofracking on T cell development and antimicrobial immunity

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $231,000

## Abstract

This exploratory research proposal addresses growing concerns about the threats of endocrine disruptor
(EDC) water pollutants released during unconventional oil and gas extraction (UOG) to human health.
Specifically, these studies focus on how a mixture of 4 UOG chemicals with thyroid hormone (TH) disrupting
activity affect the immune system, for which there is no systematic assessment to date. We have developed a
reliable, sensitive and cost-effective model system in the amphibian Xenopus that is uniquely suited to
investigate the effects of early life exposure to waterborne mixtures of UOG toxicants on immunity later in life.
 We propose a comparative biology approach in Xenopus to define how postembryonic exposure to
a representative mixture of UOG water contaminants with TH activity impacts T cell development and
weaken antimicrobial immune response later in life. Our rationale is that (1) a mixture of several EDCs
acting toward one hormone axis will allow us to address cellular mechanism leading to acute and persistent
effects of this mixture of chemicals on T cell development and function; (2) Although TH axis affects the
immune system, little is still known about the long-term biological impacts of TH disruptors on immunity; and
(3) Xenopus is a reliable, extensively characterized and widely recognized model of human perinatal
endocrinology and biomedical research on the TH axis, including dependence of TH signaling for the
differentiation of adult-type T cell immunity during metamorphosis. Other features advantageous for achieving
our goal are the external development of tadpoles, which are free of maternal influence and easily accessible
to exposure during postembryonic development, and the cost effectiveness of exposing tadpoles in large
numbers to EDCs. To test the hypothesis that developmental exposure to a mixture of TH-disruptors
associated with UOG alters T cell development, resulting in long-term perturbation of immune
homeostasis and poorer antimicrobial immunity, we will determine: (1)
acute effects of UOG-EDCs on
tadpole T cell differentiation and immune homeostasis
, by defining the impact of tadpole exposure on
homeostatic lymphocyte populations using flow cytometry, histology and transcriptomics; (2)
long-term effects
on immune homeostasis and anti-microbial immunity of developmental exposure to a mixture of TH-disruptors
persisting after metamorphosis
, by measuring changes at steady state and in response to the ranavirus FV3
(similar to poxviruses such as vaccinia, a strong CD8 T cell inducer) and Mycobacterium marinum (a pathogen
of frogs and humans, a strong CD4 T cell inducer); and (3)
TH-disruptor activity of each of the 4 UOG-EDC
alone and their potential additive and synergistic actions.
Innovative convergent findings from infection with two
different types of pathogens (pox-like FV3 and Mycobacteria) in Xenopus whose TH axis and immune system
are remarkably conserved with those of mammals will provide novel and comp...

## Key facts

- **NIH application ID:** 9977347
- **Project number:** 1R21ES030690-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JACQUES Robert
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2020-07-13 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977347

## Citation

> US National Institutes of Health, RePORTER application 9977347, Long-term effects of developmental exposure to a mixture of thyroid disruptors associated with hydrofracking on T cell development and antimicrobial immunity (1R21ES030690-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9977347. Licensed CC0.

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