# Effects of acetaminophen on prenatal brain development: an organoid model

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $197,500

## Abstract

SUMMARY
Acetaminophen (N-acetyl-p-aminophenol (APAP), also known as paracetamol) is widely used in pregnancy for
pain and fever reduction. However, an increasing number of studies suggest that APAP could negatively
influence fetal and early postnatal development, including multiple organs systems. Regarding
neurodevelopment, epidemiological studies of large cohorts have reported a significantly increased risk of
attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children prenatally
exposed to APAP. In particular, fetal brain development during the second and third trimesters of pregnancy
appears especially vulnerable to APAP based on the epidemiological and animal model studies. Despite strong
evidence for potential adverse consequences to the fetus, the mechanism by which APAP impacts human fetal
brain remains unexplored. Here, we are proposing to use human functional brain organoid models to address
this question. Brain organoids are a perfect fit for this project because they recapitulate human fetal brain
development at the transcriptional and network activity levels, as demonstrated by us and others. We
hypothesize that APAP impacts fetal brain development by dysregulating transcriptional programs
involved in early neurogenesis and synaptic signaling. We will test this hypothesis through the following
Specific Aims: (1) Identify cellular and molecular pathways, cell populations, and co-expression modules
dysregulated by APAP exposure during fetal brain development; (2) Investigate synaptic and long-term
oscillatory network activity phenotypes in response to APAP exposure to evaluate its impact on brain function.
Our study will fill in the knowledge gap regarding the safety of APAP exposure in pregnancy using relevant
human-derived brain organoid models. In addition, it will provide molecular mechanisms by which APAP could
disrupt fetal brain development and lead to neurodevelopmental diseases.

## Key facts

- **NIH application ID:** 10684055
- **Project number:** 5R21HD109616-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** LILIA M IAKOUCHEVA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2022-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10684055

## Citation

> US National Institutes of Health, RePORTER application 10684055, Effects of acetaminophen on prenatal brain development: an organoid model (5R21HD109616-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10684055. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*