Reproductive impacts of PFAS exposure revealed

A new study has discovered that PFAS exposure can significantly alter male reproductive health — even without visibly damaging sperm — while a separate study has found that PFAS levels in mothers’ blood during pregnancy are associated with their children’s brain structure and function.

PFAS (per- and polyfluoroalkyl substances) are man-made chemicals used in manufacturing products such as cooking utensils, clothes, furniture, food packaging, flooring, dental floss and firefighting foams. Nicknamed ‘forever chemicals’ due to their non-biodegradable nature, they have been found to persist in the environment and accumulate in living organisms — which is causing concern as mounting evidence suggests they may pose risks to human health.

As part of a preclinical study led by The University of Newcastle, animal subjects were exposed to PFAS-contaminated water at concentrations reflecting real-world levels in areas of Williamtown, in the Hunter Region of NSW. Here, the historic use of firefighting foam at the local RAAF base resulted in PFAS leaching into the local surface water, groundwater, and some fish species in nearby waterways.

“We emulated the levels and types of PFAS found in samples from a groundwater monitoring well — not a drinking water source — located in the Williamtown contamination zone,” explained study co-leader Dr Jacinta Martin.

“The subjects in our study were exposed to PFAS via contaminated water consumed over a 12-week period.”

Published in the journal Communications Biology, the findings in mice revealed the following:

• Developing sperm count dropped — day-to-day sperm production decreased during the PFAS exposure period.
• Male hormone levels fell — testosterone and DHT (dihydrotestosterone, a potent androgen hormone derived from testosterone), which are vital for sperm production, were reduced.
• Sperm carried hidden changes — molecules that help regulate gene expression were altered.
• Embryo development was disrupted — early embryos showed abnormal gene expression.
• Sperm still functioned normally — they could move, survive, and fertilise eggs in lab conditions, despite the molecular changes.
   

The study suggests that PFAS may not damage sperm directly, but instead alter the molecular signals sperm carry — signals that are crucial for healthy embryo development.

“This is the first time we’ve shown that PFAS exposure at environmentally relevant levels — equivalent to those detected in Williamtown — can change the molecular makeup of sperm with potential implications for disrupting embryo development,” said study co-leader Professor Brett Nixon.

“What’s striking is that the sperm still looked and functioned normally in lab conditions.

“But beneath the surface, they were carrying molecular changes that could affect the next generation.

“We also found lower levels of testosterone and DHT in male mice exposed to PFAS, and daily sperm production decreased too.”

Martin noted that the researchers also discovered some changes to gene expression which could impact the health of the embryo. “One of the predicted changes we noticed was related to body size — and the potential for offspring fathered by PFAS exposed animals to be born, or grow, significantly larger than normal,” she said.

These findings echo human studies showing lower sperm counts in men with high PFAS exposure and suggest that paternal exposure alone could have consequences for children, even if the children themselves are not directly exposed. But that’s not the only cause for concern, as researchers have previously found associations between PFAS levels in mothers’ blood during pregnancy and their children’s neurodevelopmental outcomes — with a recent study led by the University of Turku and published in The Lancet Planetary Health expanding on these findings.

As explained by lead author Aaron Barron, PFAS are ubiquitous in human blood from exposure through drinking water, food, and in some cases occupation, and our bodies do not break them down. Over the last decade, accumulating research has implicated blood PFAS levels in adverse health outcomes, especially hormone biosynthesis, metabolism and immune system function.

The new study was set within the FinnBrain Birth Cohort Study, a longitudinal birth cohort established at the University of Turku in 2011. Some of the mothers donated a blood sample during pregnancy, and their blood PFAS levels were measured by mass spectrometry at Örebro University in Sweden. Their children came back for a follow-up visit at five years old, and they underwent multimodal magnetic resonance brain imaging at Turku University Hospital. The final analysis included 51 mother–child pairs.

The researchers found that maternal PFAS were linearly associated with many aspects of their children’s brain structure. The three main brain regions involved were the corpus callosum, the brain’s largest white matter tract; the surface area and volume of the posterior grey matter volume, in the occipital lobe; and the hypothalamus, which regulates our body’s homeostasis and endocrine function. None of the associations were any different in boys and girls.

Additionally, some PFAS were associated not only with brain structure, but also brain functional connectivity based on functional MRI scans.

“We were able to measure seven different PFAS in this study, and found that individual compounds had specific associations with offspring brain structure, and in some cases two different PFAS had opposite relationships with the same brain region,” said Professor Tuulia Hyötyläinen from Örebro University.

The PFAS could be divided into two groups based on their chemical structure — whether they contain a carboxylic acid or a sulphonic acid functional group. In most cases, except for in the hypothalamus, the carboxylate-containing PFAS were the ones that were more strongly associated with brain outcomes in children.

“At the moment, it is unclear whether PFAS are directly affecting brain development, although it’s known that they pass the placenta and the blood–brain barrier to accumulate in the brain, and can disturb developing brain cells,” said Professor Hasse Karlsson from the University of Turku. “It’s also unclear whether these associations are harmful, beneficial or neutral, and future studies will be needed to determine the functional implications of our findings.”

Image credit: The University of Newcastle.