# In vitro molecular interrogation of SSRI antidepressants for teratogenic potential

> **NIH NIH R03** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $77,750

## Abstract

Proposal Abstract
 Depression affects many women of reproductive age, and it needs to be treated adequately during as
well as before pregnancy to maintain maternal and fetal health. However, teratogenic potentials of common
antidepressants, such as selective serotonin reuptake inhibitors (SSRI), are still unclear and controversial.
Teratogenicity of drugs is strongly influenced by their concentrations that are exposed to developing embryos.
However, how much of medications were actually taken during the critical stages of pregnancy is largely
unclear in epidemiologic studies. Hence, it is difficult to evaluate dose-effect relationship, which may be
contributing to the conflicting data on SSRI teratogenicity. Another unresolved issue is regarding the
mechanism by which SSRI exert teratogenic potential. The therapeutic action of SSRI is to inhibit the
serotonin transporter to elevate the neurotransmitter serotonin. However, it is still unclear whether the
serotonin transporter plays crucial roles in embryo development. These issues need to be resolved to better
understand the teratogenic potential of SSRI. The goal of the proposed project is to elucidate the molecular
properties of common SSRI antidepressants, specifically on the concentration-adverse effect relationship and
molecular targets that are pertinent to teratogenicity, using the novel assay platform of human embryonic stem
(ES) cells that my lab established. Specifically, we will (1) determine exposure levels of SSRI that impact
human stem cell development, (2) test the hypothesis that teratogenic effects of SSRI are due to inhibition of
WNT signaling, and (3) test whether the therapeutic target molecule of SSRI is dispensable for teratogenicity.
These studies should yield valuable information on teratogenic potential of SSRI, which will help in the design
of more focused studies in human and in interpreting epidemiologic data.

## Key facts

- **NIH application ID:** 10137290
- **Project number:** 5R03HD101735-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** YUSUKE MARIKAWA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $77,750
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137290

## Citation

> US National Institutes of Health, RePORTER application 10137290, In vitro molecular interrogation of SSRI antidepressants for teratogenic potential (5R03HD101735-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10137290. Licensed CC0.

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