# Prenatal immune programming of sex differences in depression and CVD risk. Supplement to Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation.

> **NIH NIH U54** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $13,661

## Abstract

This application is a request for diversity supplemental funding for Ms. Monique Martinez to initiate her
graduate studies in the laboratory of Dr. Taben Hale at the University of Arizona. This project examines the
fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, an important system for regulating and
coordinating adrenal glucocorticoid (GC) secretion to allow for proper adaptation to stressors and maintain
physiological homeostasis. As part of the U54 program that oversees this project, Ms. Martinez will be a
member of the training program and be exposed to the educational mission that the SCORE program is
developing. Ms. Martinez will also work closely with the other PIs in the SCORE program. This includes Dr. Jill
Goldstein who is mPI of the Program and the Lead of Project 1 and Dr. Stuart Tobet who is mPI of the program
and PI of project 3. During development, increased exposure to GCs through prenatal stress or inflammation
can disrupt fetal brain programming and increase risk for long-term health consequences. The foundation for
this hypothesis is that the in-utero environment programs the brain and increases the risk developing long-term
complex diseases in adulthood. Diseases with fetal origins include depression and anxiety-like disorders,
social impairments, and cardiometabolic disorders. Common to each of these, is a dysregulation of the
autonomic nervous system. The overarching goal of Ms. Martinez’ project is to examine the effects of in utero
overexposure to GCs and inflammation on hypothalamic and cardiac development resulting in autonomic
dysregulation. Preliminary data has shown that rodents display cardiovascular and behavioral changes after in
utero exposure to the synthetic GC, dexamethasone (DEX). Specifically, late gestation exposure to DEX
results in female-biased autonomic dysregulation that is characterized by an increase in sympathetic and a
withdrawal of parasympathetic input to regulation of heart rate and blood pressure under basal and stress
conditions. Healthy females have been shown to show a greater reliance on parasympathetic input, as
compared to males. Preliminary findings suggest that prenatal DEX disrupts this normal development. Puberty
is known to be a critical developmental period for programming of the autonomic nervous system. Therefore,
studies outlined in this proposal test the hypothesis that puberty is a critical period for programing autonomic
nervous system, and that late gestation perturbations negatively impact these responses. Autonomic function
will be assessed in rats exposed to excess glucocorticoids (DEX) or inflammation (TLR7 agonist, resiquimod)
in utero pre- (3-4 weeks of age) and post-puberty (8-10 weeks of age). To determine the degree to which these
effects are peripherally mediated, cardiac responses to sympathetic and parasympathetic nervous system
agonists will be evaluated ex vivo to remove any neural influences and reflex responses. These studies will
have impli...

## Key facts

- **NIH application ID:** 10846952
- **Project number:** 3U54MH118919-04S3
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** JILL M GOLDSTEIN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $13,661
- **Award type:** 3
- **Project period:** 2020-02-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846952

## Citation

> US National Institutes of Health, RePORTER application 10846952, Prenatal immune programming of sex differences in depression and CVD risk. Supplement to Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation. (3U54MH118919-04S3). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10846952. Licensed CC0.

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