Forever chemical disturbs early development in stem cell model
· Medical Xpressby Jelaine Legaspi, Karolinska Institutet
edited by Lisa Lock, reviewed by Andrew Zinin
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Research using stem cell-derived models of early human development suggests that PFOS, a persistent substance belonging to the PFAS group, can interfere with processes critical for early germ cell and embryonic development. The study, from Karolinska Institutet, is published in the journal Human Reproduction Open.
PFAS are a large group of synthetic chemicals used in products such as water-repellent materials, food packaging, cosmetics and many other consumer goods. Because these substances break down extremely slowly, they can persist in the environment for decades, which has earned them the nickname "forever chemicals." PFAS can also accumulate in the human body over time.
In this study, researchers investigated three already regulated but highly persistent PFAS compounds: PFOS, PFOA and PFHxS. Using human pluripotent stem cells, they generated a three-dimensional cellular model recapitulating several aspects of early human development occurring shortly after embryo implantation in the uterus, including the formation of primordial germ cells, the precursors of sperm and eggs.
"Our study highlights the potential of stem cell–based models to investigate how environmental chemicals affect the earliest stages of human development, a period that is otherwise difficult to study," says João Pedro Alves-Lopes, assistant professor at the Department of Women's and Children's Health, Karolinska Institutet, and lead author of the study.
The disrupting effects occur at levels found in the blood of pregnant women
Of the three substances studied, PFOS had the most pronounced effect. During the four-day experiments, the embryo-like structures grew more slowly and remained smaller than untreated controls, an effect observed even at the lowest concentration tested: 7 nanomoles per liter. This baseline concentration was selected because it corresponds to PFOS levels measured in the blood serum of pregnant women participating in the Swedish SELMA study.
Although early germ cells still formed following PFOS exposure, their gene expression patterns were substantially altered. At the baseline concentration tested, the activity of 746 genes differed from that of the control group, leading to the repression of biological processes involved in development and cell signaling.
"Our results suggest that even at low concentrations, PFOS can perturb fundamental processes of early human embryonic and germ cell development, highlighting the potential impact of everyday environmental exposures on reproductive health," says Alves-Lopes.
It is important to note that, although this model captures key aspects of early post-implantation development, it does not fully recapitulate a human embryo or the complex environment of the womb. Consequently, complementary studies, including animal models and human epidemiological data, will be needed to validate the long-term consequences of early prenatal exposure to PFAS, including the many family-related compounds that remain largely uncharacterized and could be efficiently screened using this stem cell–based platform.
More information
Silvia Pérez Casasús et al., PFOS disrupts the development of early germline and surrounding embryonic soma at environmentally relevant exposure levels, Human Reproduction Open (2026). DOI: 10.1093/hropen/hoag099
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