# Immunologic Contributions to the Endometriosis Phenotype

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $21,461

## Abstract

PROJECT SUMMARY
Endometriosis, the presence of endometrial tissue at an extra-uterine site, is a common yet enigmatic
gynecologic disease that dampens the quality of life for approximately 10-15% of reproductive-aged women.
Although endometriosis is regarded as a benign condition, many women with this disease experience chronic
episodes of debilitating pain, dyspareunia, dysmenorrhea, and/or infertility. Numerous theories have attempted
to explain disease pathogenesis including retrograde menstruation, a genetic predisposition, and altered
differentiation of non-uterine cells. Unfortunately, theories to date have failed to explain all incidences of disease
occurrence. Thus, I am exploring the possibility that endometriosis is an adult-onset disease that emerges due
to an early life disruption of endocrine-immune cross-communication. I hypothesize that an in utero toxicant
exposure trains bone marrow-derived immune progenitor cells (BMDCs) and subsequently promotes the
development of endometriosis in adulthood. Immune cell training refers to the development of memory of a
previous infection, but it is unknown whether immune cells similarly “remember” a past toxicant exposure.
Nevertheless, our laboratory has shown that in utero TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure in
mice results in a loss of uterine progesterone (P4) sensitivity and hyperinflammation as seen in women with
endometriosis. Herein, I will utilize our established mouse model of toxicant exposure to determine if in
utero TCDD exposure induces immune cell training prompting the development of the endometriosis-like uterine
phenotype in adult mice. In Specific Aim 1, I will examine the relationship between toxicant-mediated peritoneal
inflammation and reproductive dysfunction by characterizing the intraperitoneal immune phenotype and uterine
phenotype of TCDD-exposed mice compared to wild-type C57/BL6 (WT) mice. Furthermore, I will determine if
TCDD-mediated alterations of immune cells directly contribute to uterine dysfunction by adoptively
transferring BMDCs from TCDD-exposed mice to control recipient mice. In Specific Aim 2, I will elucidate the
molecular mechanisms underlying the TCDD-generated phenotype by examining the epigenetic, metabolic, and
functional status of TCDD-exposed immune cells in comparison to unexposed immune cells. Overall,
determining the specific contribution of immune cells to reduced P4 sensitivity within the uterus and identifying
targetable pathways will determine the potential utility of immune cells as a diagnostic and/or therapeutic
target. This proposal builds upon preliminary data that I have obtained and will provide me with the training I
seek in reproductive toxicology, reproductive immunology, immunotoxicology, and immunometabolism. Aside
from gaining this knowledge and technical skills, I will also gain necessary experience in data analysis,
generation of manuscripts, communication of my results to scientific and lay audiences, and th...

## Key facts

- **NIH application ID:** 10913967
- **Project number:** 5F31ES034957-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Victoria Renee Stephens
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $21,461
- **Award type:** 5
- **Project period:** 2023-02-01 → 2024-08-18

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913967

## Citation

> US National Institutes of Health, RePORTER application 10913967, Immunologic Contributions to the Endometriosis Phenotype (5F31ES034957-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10913967. Licensed CC0.

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