# Sex-dependent effects of prenatal alcohol exposure on developmental programming

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2022 · $334,690

## Abstract

PROJECT SUMMARY
Prenatal alcohol exposure (PAE) is associated with developmental, cognitive, behavioral, and physical
abnormalities termed Fetal Alcohol Spectrum Disorders (FASD). With a prevalence ranging from 2 to 5 in 100
children and an estimated added annual cost of $21,000 for an individual afflicted with FASD, therapies aimed
at treating FASD will be of significant societal benefit. Our goal is to identify molecular mechanisms through
which alcohol alters the developing fetus and to use this information to advance targeted interventions that
reverse or reduce the long-term consequences of PAE.
PAE “programs” development of the organism, producing changes that can persist throughout the lifespan. In
many cases, the effects of PAE are mediated by glucocorticoids (GCs) acting via glucocorticoid receptors
(GRs) and are influenced by the sex of the organism. We hypothesize that PAE modifies the in utero
programming of GRs in a sex- and development-specific manner as the result of differential effects of PAE on
placental and fetal brain levels of 1.) 11β-HSD1 and 11β-HSD2, which catalyze interconversion of active and
inactive GC, and 2.) the long noncoding RNA Growth arrest-specific 5 (Gas5), which binds to the GR DNA-
binding domain, inhibiting GR-dependent gene expression. These studies will identify effects of PAE on
microRNA-mediated mechanisms that regulate GR programming. Additionally, we assess the role of placental
exosomes as mediators of the effects of PAE on fetal brain Gas5. Elucidation of the effects of PAE on
placental 11β-HSDs, Gas5 and exosomes may serve to identify 1.) biomarkers for identification of alcohol
consumption during human pregnancy, 2.) predictors of progeny outcomes, and 3.) novel targets for the
treatment of FASDs.

## Key facts

- **NIH application ID:** 10380609
- **Project number:** 5R01AA026583-04
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Nikolaos Mellios
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $334,690
- **Award type:** 5
- **Project period:** 2019-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380609

## Citation

> US National Institutes of Health, RePORTER application 10380609, Sex-dependent effects of prenatal alcohol exposure on developmental programming (5R01AA026583-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380609. Licensed CC0.

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