# The Impact of Oral Contraceptives on Neuron-derived Exosomal miRNA Expression in the Developing Brain

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2024 · $212,345

## Abstract

Project Summary
Oral contraceptives (OCs) contain synthetic estrogen and progesterone and are prescribed to millions of women
in the United States for some period during their reproductive years. OCs also are approved for use after onset
of menarche, which is well before brain maturation is complete. Among adult women, imaging studies suggest
that use of OCs is associated with changes in brain structure and function. It is likely that cellular level changes
also occur in the brain with OC use, particularly during the neurobiologically dynamic adolescent/young adult
years. Surprisingly, there are no studies investigating the potential impact of OCs on the developing female brain,
establishing a critical need to determine the potential effects of synthetic hormones on early life brain biology. In
this application, we propose to investigate neuron-derived exosome (NDE) microRNA (miRNA) as a
neurobiological index. Exosomes are membrane-bound sacs that transport biologically active materials
throughout the body to promote homeostasis and facilitate intercellular signaling. Exosomes are released by
most tissues, including neurons, as routine physiology, easily crossing the blood brain barrier. Exosomes are
also present in many different biofluids. Alterations to exosome characteristics have been associated with the
pathophysiology of several cancers and neurodegenerative disorders (e.g., Alzheimer’s). It is hypothesized that
differential expression of NDE miRNAs may aid identification of aberrations in biological pathway regulation as
a function of OC exposure. To investigate the effect of OCs on early life neurobiology, NDE miRNA expression
in young women prescribed OCs will be compared to natural cycling, OC naïve females. We will recruit 60 young
women (15-22 years), including N=30 young women using OCs > 6 months and 30 natural cycling, OC naïve
young women. This study will take advantage of the comprehensive Affymetrix GeneChip array to inventory
miRNAs to index brain-based cellular perturbations. The OC use group will participate in two study visits, for a
total of 60 person-time points while the natural cycling, OC naïve group will complete four study visits during the
early follicular, late follicular, ovulation, and luteal phases for a total of 120 person-time points. As a first step, it
will be necessary to understand whether NDE miRNA expression fluctuates as a function of hormonal milieu.
Thus, Aim 1 will characterize NDE miRNA expression across the menstrual cycle while Aim 2 will determine
whether NDE miRNA differs across the active and inactive pill phases. Finally, Aim 3 will characterize the NDE
miRNA landscape in OC users. NDE miRNAs identified in Aim 3 also will be probed with complementary network-
based analyses to identify involved neurophysiological pathways. Insights from this study will clarify whether
there is scientific merit to proceed to in vivo studies as well as causally informative, longitudinal studies of OCs
to elucida...

## Key facts

- **NIH application ID:** 10989061
- **Project number:** 1R21HD113953-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Roxann Roberson-Nay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $212,345
- **Award type:** 1
- **Project period:** 2024-08-06 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10989061

## Citation

> US National Institutes of Health, RePORTER application 10989061, The Impact of Oral Contraceptives on Neuron-derived Exosomal miRNA Expression in the Developing Brain (1R21HD113953-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10989061. Licensed CC0.

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