Per- and polyfluoroalkyl substances (PFAS) – a group of nearly 10,000 persistent chemicals – are linked to a range of health risks, including effects on pregnant women and their unborn children. While the placenta normally serves as a protective barrier for the fetus, the extent of fetal PFAS exposure during early pregnancy has remained unclear.
Researchers at the Helmholtz Centre for Environmental Research (UFZ), in collaboration with Dessau Municipal Hospital, have developed an advanced 3D placenta model to better study these risks. Their findings, published in Environmental Research, reveal that PFAS can disrupt placental function, particularly during the first trimester – a critical period for fetal organ development.
The placenta regulates the transfer of nutrients, gases, and metabolic products between mother and fetus, ensuring healthy growth. The first 90 days of pregnancy are especially important, as the baby’s organs begin forming. Although the placenta has mechanisms to block harmful substances, PFAS can accumulate in the body, potentially impairing fetal development and increasing the risk of miscarriage.
“For accurate risk assessment, it is crucial to document PFAS exposure during the first trimester,” said UFZ reproductive scientist Dr. Violeta Stojanovska, the study’s principal investigator. Previous studies have largely relied on PFAS measurements in maternal blood or placentas collected late in pregnancy, or on simplified cell models using individual PFAS compounds rather than realistic mixtures.
In their study, UFZ researchers and Dessau Municipal Hospital scientists analyzed first-trimester placental tissue from 31 women and identified six PFAS compounds – perfluorononanoic acid, perfluorooctanesulfonic acid, perfluorobutanoic acid, perfluorooctanoic acid, perfluorohexanesulfonic acid, and perfluorodecanoic acid. “We focused on these PFAS because they were present in high concentrations and prior studies suggested they might contribute to pregnancy complications,” said Yu Xia, doctoral candidate and lead author. The team then created a placenta-relevant PFAS mixture for testing in a 3D trophoblast model.
Trophoblasts are placental cells that invade maternal tissue early in pregnancy and establish contact with the mother’s bloodstream. Unlike flat 2D cultures, 3D models allow trophoblasts to grow in spherical structures that closely resemble early placental development. This enables researchers to study key placental functions, including hormone production and tissue invasiveness.
Exposure to the PFAS mixture disrupted these functions. Placental cells showed reduced invasiveness, which is essential for nutrient transfer to the fetus. Gene analysis revealed that PFAS also impaired apoptosis (programmed cell death) and proliferation – processes that must remain balanced for proper placental development.
The study further found that PFAS exposure lowered β-hCG production, the first hormone produced by the placenta. β-hCG supports progesterone production, which maintains a healthy uterine lining and prevents fetal rejection. “Although these changes may seem minor individually, collectively they could have a significant impact on pregnancy progression,” Stojanovska said.
The research highlights the need for more precise monitoring of PFAS exposure in early pregnancy and suggests that even low-level exposure may pose risks to fetal development.
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