Researchers at the Helmholtz Centre for Environmental Research (UFZ), in collaboration with Dessau Municipal Hospital, have advanced a 3D placenta model to study the effects of per- and polyfluoroalkyl substances (PFAS) on early pregnancy. PFAS are a group of nearly 10,000 chemical compounds known for their persistence in the environment and potential health risks, including those affecting pregnant women and fetuses.
The placenta is responsible for regulating nutrient, gas, and metabolic exchange between mother and fetus. The first trimester is particularly critical as organ development begins during this period. While the placenta acts as a barrier against harmful substances, PFAS can accumulate in the body and disrupt fetal development. Severe cases may increase miscarriage risk.
"For an accurate risk assessment, it is important to document PFAS exposure more precisely, especially during the first trimester of pregnancy," said Dr Violeta Stojanovska, UFZ reproductive scientist and principal investigator. She noted that most studies so far have focused on later stages of pregnancy or used simplified models that do not reflect real-world PFAS mixtures.
In their study with Dessau Municipal Hospital, researchers extracted six types of PFAS from placental tissue samples taken from 31 women in their first trimester. "These PFAS were relevant for our investigations because we detected them in high concentrations in placenta and there was literature indication that they might trigger pregnancy complications," said Yu Xia, doctoral candidate and lead author. The team then created a mixture reflecting these compounds to test its impact using a 3D trophoblast model designed to simulate placental exposure.
Trophoblasts are cells essential for establishing contact between maternal tissue and bloodstream early in pregnancy. "The main advantage of the 3D models is that trophoblast cells grow in a spherical structure, which closely mimics the cell organisation seen in early placental development, unlike the flat arrangement in 2D cultures," said Stojanovska.
When exposed to the PFAS mixture, these models showed impaired function: reduced ability of placental cells to invade maternal tissue—a process vital for proper fetal growth due to its role in nutrient transfer—was observed.
Gene expression analysis indicated that key processes such as apoptosis (programmed cell death) and proliferation (cell growth needed for placental development) were disrupted by PFAS exposure. "The two processes are kept in natural balance during the development of the placenta. However, this balance is disturbed when the placenta is exposed to high PFAS concentrations," Stojanovska explained.
Additionally, researchers found lower production levels of β-hCG—the hormone produced first by the placenta that regulates progesterone production necessary for maintaining healthy uterine lining and preventing fetus rejection—after exposure to PFAS mixtures. "These minor changes haven't received much attention so far, but taken collectively might cause significant impact on pregnancy progression," added Stojanovska.
"The study emphasizes the harmful effects of the PFAS mixture on trophoblast function and thus the potential risks to placental health and the outcome of the pregnancy," said Prof Ana Zenclussen, Head of UFZ’s Department of Environmental Immunology. She noted that 3D trophoblast models provide valuable insights into assessing risks associated with environmental contaminants like PFAS.
