Pivotal new findings show that PFAS exposure can markedly affect early placental function, raising concerns about fetal health from the very start of pregnancy. PFAS, a broad family of nearly 10,000 persistent chemicals, linger in the environment and have been linked to health issues for both expectant mothers and their babies. While the placenta acts as a critical shield for the developing fetus, prior research often failed to quantify real exposure levels to PFAS during the earliest weeks of gestation. Now, researchers at the Helmholtz Centre for Environmental Research (UFZ), in collaboration with Dessau Municipal Hospital, have refined a three-dimensional placental model to better assess risks associated with PFAS in early pregnancy. Their study, published in Environmental Research, demonstrates that PFAS can disrupt placental function, particularly during the first trimester when fetal development is most vulnerable.
The placenta regulates the exchange of nutrients, oxygen, and metabolic byproducts between mother and fetus, supporting healthy growth. The initial 90 days of gestation are especially crucial as organ systems begin forming. Although placental barriers exist to limit harmful substances reaching the fetus, PFAS can accumulate in the body and interfere with fetal development, with potential miscarriage risks in severe cases. One UFZ reproductive scientist, Dr. Violeta Stojanovska, emphasizes that precise documentation of PFAS exposure—especially in the first trimester—is essential for accurate risk assessment. Historically, knowledge in this area has been limited because many studies rely on PFAS measurements taken later in pregnancy or on simplified cellular models that test single PFAS compounds rather than mixtures.
To address this gap, the UFZ team partnered with Dessau Municipal Hospital, part of Brandenburg Medical School, and selected six PFAS compounds (perfluorononanoic acid, perfluorooctanesulfonic acid, perfluorobutanoic acid, perfluorooctanoic acid, perfluorohexanesulfonic acid, and perfluorodecanoic acid) that appeared in notable concentrations within first-trimester placental tissue from 31 women. Lead author Yu Xia notes these chemicals were particularly relevant because they were detectable at high levels in the placenta and had literature suggesting possible pregnancy complications. These six PFAS were then combined into a placenta-relevant mixture for testing in a 3D trophoblast model to simulate placental exposure.
Trophoblasts, the placental cells that invade maternal tissue to establish a connection with the maternal bloodstream, were studied in three-dimensional form. The 3D model fosters a spherical arrangement that more accurately reflects early placental architecture than flat, two-dimensional cultures. This setup enabled examination of several key placental functions, including hormone production and cellular invasiveness.
Exposure of the 3D trophoblasts to the PFAS mixture impaired placental performance, notably reducing the cells’ invasive capacity, a critical process that facilitates nutrient transfer from mother to fetus and supports proper fetal growth.
Gene expression analyses indicated that two essential processes—apoptosis (programmed cell death) and proliferation (cell growth vital for placental development)—were also disrupted by PFAS. Under normal placental development, these processes maintain a delicate balance; however, high PFAS levels appear to disturb this equilibrium.
Additionally, PFAS exposure lowered the production of β-hCG, the first placental hormone that stimulates progesterone production and helps maintain a healthy uterine lining while reducing the risk of fetal rejection. Even minor decreases in β-hCG could signal broader hormonal regulation issues that cumulatively affect pregnancy progression, according to Stojanovska.
The team, including Prof. Ana Zenclussen, head of UFZ’s Department of Environmental Immunology, concludes that PFAS mixtures can compromise trophoblast function and threaten placental health and pregnancy outcomes. The 3D trophoblast model thus provides a powerful tool for more comprehensive PFAS risk assessment during early pregnancy, highlighting concerns that might be overlooked by traditional 2D models or late-pregnancy sampling.
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