Polyoxyethylene tallow amine and glyphosate exert different developmental toxicities on human pluripotent stem cells-derived heart organoid model

Hao Sun ¹, Zhazheng He ², Yao Gao ²

⁰State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, China.

The Science of the Total Environment +

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February 5, 2024

View abstract on PubMed

Summary

Human heart organoids (hHOs) effectively model Glyphosate-based herbicide (GBH) toxicity, revealing polyoxyethylene tallow amine (POEA) as the primary cardiac developmental toxicant. This method aids in identifying environmental risks and understanding toxic mechanisms.

Area Of Science

Developmental Biology
Toxicology
Biotechnology

Background

Early heart development is sensitive to environmental factors.
Animal models have limitations in assessing human cardiac developmental risks.
Human heart organoids (hHOs) offer a promising alternative due to their biological consistency.

Purpose Of The Study

To evaluate the reliability of hHOs for assessing cardiac developmental toxicity of Glyphosate-based herbicides (GBHs).
To investigate the specific role of GBH components in cardiogenesis toxicity.
To elucidate the toxic mechanism of GBHs on heart development.

Main Methods

Utilized human heart organoids (hHOs) to assess cardiac developmental effects.
Exposed hHOs to Glyphosate-based herbicides (GBHs), polyoxyethylene tallow amine (POEA), and Glyphosate.
Analyzed disruption of heart contraction, cardiomyocyte isoform commitment, and epicardial hyperplasia.

Main Results

Polyoxyethylene tallow amine (POEA) was identified as the dominant contributor to GBH cardiotoxicity.
Exposure to POEA (alone or with Glyphosate) disrupted heart contraction and cardiomyocyte differentiation in hHOs.
Glyphosate alone induced only mild epicardial hyperplasia, while POEA demonstrated significant cardiotoxicity.

Conclusions

Human heart organoids (hHOs) are effective for evaluating environmental risk factors and predicting cardiogenesis toxicity.
POEA is the primary toxic component in GBHs responsible for cardiac developmental effects.
This study provides a methodological framework for assessing environmental toxicants and understanding their mechanisms.

Keywords:

Assessment model Glyphosate-based herbicides (GBHs) Human heart organoids (hHOs) Polyoxyethylene tallow amine (POEA) Single and combined exposure