# Chemical disruption of placental thyroid hormone signalling: a systematic review that highlights sex-specific effects

## TL;DR

This review shows that chemicals can disrupt thyroid hormone signaling in the placenta, with effects varying based on the sex of the fetus.

## Contribution

The paper systematically reviews sex-specific effects of chemical exposure on placental thyroid hormone signaling.

## Key findings

- Chemicals like pollutants and pharmaceuticals disrupt placental thyroid hormone signaling through transporters and enzymes.
- Sex-specific effects were observed, with male and female fetuses responding differently to chemical exposure.
- Choriocarcinoma cell lines may not accurately represent human placental processes.

## Abstract

Thyroid hormones are crucial for growth, brain development, metabolism, and organ maturation in developing foetuses. Until 12–14 weeks of gestation, the foetus depends on maternal thyroid hormones before its own thyroid gland begins functioning. Environmental chemical and medication exposure during pregnancy may affect the thyroid hormone supply to the foetus by interfering with placental transport carriers and metabolism. This systematic review evaluated chemical effects on thyroid hormone passage from maternal to foetal circulation, modulated by transporters and enzymes. A search of PubMed, Scopus, and Web of Science identified 24 relevant studies published between 1900 and 2024, including 4 epidemiological studies, 8 in vivo animal studies, and 15 in vitro studies. The review found evidence that persistent organic pollutants, flame retardants, endocrine disrupting chemicals, pharmaceuticals, and other substances can disrupt placental thyroid hormone signalling through various mechanisms. These include alterations in transporter expression and enzyme activity in the placenta. Several studies observed sex-specific effects, with male and female foetuses showing different responses to chemical exposure. In some cases, sex differences were in the degree of change, while in others, the same chemical had opposite effects based on foetal sex. However, many studies used choriocarcinoma cell lines, which may not fully replicate human placental processes. This review highlights the need for further research to elucidate chemical exposure's impact on foetal thyroid hormone status and the role of foetal sex using human physiologically relevant models.

The online version contains supplementary material available at 10.1007/s00204-025-04203-z.