Researchers have shown that nanoparticles found in the placenta disrupt essential tissue functions and the release of signaling factors necessary for a baby’s healthy development.
Exposure to nanoparticles during pregnancy is increasingly being linked to harmful effects on embryo-fetal development, but their direct impact has been difficult to pinpoint. This motivated a team of scientists at the Swiss Federal Laboratories for Materials Science and Technology (Empa) to uncover the truth.
“Pregnant women and the developing fetus are highly vulnerable populations, and there is increasing evidence that adverse in utero exposures to certain nanomaterials is associated with pregnancy complications and the development of diseases in later life,” said Tina Buerki-Thurnherr, lead scientist on the study published in Advanced Science, in an email. “However, the mechanisms […] are largely unknown.”
Buerki-Thurnherr and her colleagues therefore set out to examine the effects of nanoparticles on the human placental secretome — a regulated collection of signaling molecules, including proteins, lipids, nucleic acids, and extracellular vesicles, released from the placenta.
‘The secretome is essential and tightly orchestrated, it’s required for proper embryo-fetal development and a successful pregnancy,” said Buerki-Thurnherr.
Common nanoparticles build up in the placenta
Metal oxide nanoparticles found in numerous consumer products and pollution are raising concerns regarding their potential impact on pregnancy. The team specifically looked at silicone dioxide (SiO2), titanium dioxide (TiO2), and diesel exhaust nanoparticles as numerous animal studies have already shown that TiO2 and SiO2 nanoparticles can induce placental dysfunction, reduce fetal weight, or lead to higher fetal resorption.
“Furthermore, epidemiological studies associated air pollution particles with intrauterine growth restriction, autism spectrum disorder, as well as prenatal complications and postnatal diseases related to the respiratory system,” wrote the team in their paper.
Importantly, these particles have been found to but build up in the placenta, with limited transfer to the fetus, suggesting they might harm the fetus indirectly through effects on the placenta. For this reason, Buerki-Thurnherr and her team sought to identify potential fetal toxicity resulting indirectly from nanoparticles affecting placenta viability, signaling factor release, and changes to the placental secretome, which could negatively impact blood vessel formation and early brain development.
“Disturbances of proper blood vessel formation in the placenta or embryo-fetal tissues may lead to adverse pregnancy outcomes since it is well-established that aberrant vascular physiology is involved in the pathogenesis of many pregnancy disorders,” explained Buerki-Thurnherr.
Rather than conducting animal studies, the team used placental tissue samples from early and late stages of pregnancy to create a realistic human model. “We aimed to apply concentrations that could reflect a realistic human exposure by extrapolating from concentration values that were previously measured in human placenta tissue,” added Buerki-Thurnherr.
Indirect toxicity and what’s next
The team’s findings aligned with previous research but provided new insights. They aim to inform policy and advocate for comprehensive toxicity studies that consider indirect placenta-mediated effects, not just direct impacts on fetuses exposed to products containing these nanoparticles.
“We uncovered that the investigated nanoparticles induced […] stage-specific perturbations of the placental secretome, which impaired [blood vessel development] but did not affect early neurodevelopmental processes,” said Buerki-Thurnherr. “We found that media from nanoparticle-exposed placental explants reduced blood vessel density, length and branching as well as impaired the formation of new blood vessels.”
They also found that the nanoparticles disrupted the secretion of various substances that control blood vessels, hormones, and immune responses. This disruption was more significant in early placental tissue, a crucial time when healthy development relies heavily on external signals.
The negative effects were induced from a single, short-term exposure, and interestingly, the outcomes were also material specific. “For instance, the metal oxide nanoparticles (silicon dioxide and titanium dioxide) dysregulated several pregnancy hormones, inflammatory/immune factors and lysosomal proteins with known functions in immune responses and blood vessel remodeling, while diesel exhaust particles affected a distinct set of inflammatory and vascular factors,” said Buerki-Thurnherr.
Further investigation is needed to verify these results in an intact organism as the placenta models used in the current study do not fully reproduce human pregnancy. Future studies will also investigate whether a dysregulated placental secretome could affect the development of other fetal organs besides blood-vessels.
“We are currently developing a placenta-embryo-chip model to gain further insights into developmental toxicity mechanisms of nanomaterials on early embryonic development,” added Buerki-Thurnherr.
“We believe that our findings will raise the awareness on the importance of the placenta for maternal-fetal health and advocate that this organ should be represented in future developmental toxicity assessment of nanomaterials in order not to miss indirect placenta-mediated effects, which may result in adverse pregnancy outcomes,” she concluded.
Reference: Tina Buerki-Thurnherr, et al., Nanoparticles Dysregulate the Human Placental Secretome with Consequences on Angiogenesis and Vascularization, Advanced Science (2024). DOI: 10.1002/advs.202401060
