Bisphenol A causes sex-specific changes in metabolism and the immune system

Close-up of a can of crushed tomatoes being opened.

Bisphenol A can, for example, be found in the coating on the inside of tin cans. The new study shows that exposure to the chemical led to altered gene expression. Photo: Getty Images

Even small amounts of bisphenol A can lead to long-term health effects. When researchers studied adult rats exposed in the foetal stage, they found that females had developed a more masculine and males a more feminine gene expression pattern. This led to females progressing towards a cancer-like state, while males progressed towards metabolic syndrome, which can increase the risk of diabetes and heart disease.

Bisphenol A is a synthetic chemical with oestrogen-like properties that is commonly used in food packaging materials. The substance is banned in many products, but is still present in some packaging. Levels of bisphenol A in people’s bodies are often above levels considered safe, with previous research showing that the substance can cause adverse health effects.

Females masculinised and males feminised

In the current study, researchers investigated how bisphenol A affects the body during the foetal stage. Pregnant rats were given drinking water containing bisphenol A. Two doses of bisphenol A were studied, one corresponding to the daily human exposure (0.5 micrograms per kilogram of body weight per day) and a higher dose considered safe in 2015 (50 micrograms per kilogram of body weight per day). The researchers then analysed gene expression in the bone marrow and biological markers in the blood of the adult offspring.

“We saw lasting effects in the adult rat,” says Thomas Lind, the study’s first author. “Even very low doses changed how the genes were expressed. Females were masculinised and males were feminised. Both sexes experienced metabolic changes − females progressed towards a cancer-like state while males showed signs of progression towards metabolic syndrome, which can increase the risk of diabetes and heart disease.”

Strengthens the link between bisphenol A and PCOS

The researchers also saw an impact on the immune system. The activity of some immune cells, the T cells, increased in males but decreased in females. This finding confirms what previous studies have shown, namely that these immune cells are involved in changes caused by bisphenol A exposure.

The analysis of the blood markers showed several sex-specific changes. In males, a disturbed lipid profile was observed, with signs of increased metabolism and thyroid-related hyperactivity. In females, there were reduced glucose levels, elevated insulin levels and signs of increased testosterone activity, a pattern reminiscent of polycystic ovary syndrome (PCOS).

“The results also corroborate previous human studies, where women with the hormone disorder PCOS have exhibited higher levels of bisphenol A in the blood, which correlates with an increased influence of male sex hormones. This reinforces the findings of other studies linking bisphenol A exposure to declining fertility in women,” says Lind.

Study confirms need for stricter regulation

The results suggest that reducing the use of bisphenol A in food packaging could help prevent health risks.

“The study shows that even very small amounts of bisphenol A can affect health later in life. Although the results are based on experimental data, they support the European Food Safety Authority’s decision to significantly lower the tolerable daily intake of the substance by 20,000 times to 0.2 nanograms per kilogram of body weight per day.”

Sandra Gunnarsson

Black and white portrait of Thomas Lind.

Thomas Lind, researcher at the Department of Medical Sciences. Photo: Linn Areskoug

Publication

Lind T, Dunder L, Lejonklou MH, Lind PM, Melhus H, Lind L. Developmental low-dose bisphenol A exposure leads to extensive transcriptome female masculinization and male feminization later in life. Commun Med (Lond). 2025 Oct 1;5(1):410. doi: 10.1038/s43856-025-01119-8. PMID: 41034487; PMCID: PMC12488919.

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