“Forever chemicals” may be linked to reproductive health risks and pregnancy complications, review suggests

Exposure to per- and polyfluoroalkyl substances (PFAS) may impact female fertility, pregnancy and birth outcomes, according to the results of a recent review published in F&S Reviews, the journal of the American Society for Reproductive Medicine.

PFAS refer to a group of more than 9,000 synthetic chemicals that have been used and manufactured since the 1940s, appearing in products such as nonstick cookware, food packaging and water-resistant coatings. PFAS are called “forever chemicals” because they don’t break down easily in the environment or the body.

The review was conducted by a team of researchers, including corresponding author Fang Wang, M.D., from the department of reproductive medicine at Lanzhou University in China. Wang and her team reviewed evidence published in both the United States and China between 2023 and 2026. The evidence suggests that PFAS can cross critical physiological barriers and accumulate in reproductive tissues, raising concerns about potential risks before, during and after pregnancy.

“The weight of evidence links prenatal exposure with major obstetric outcomes, including hyperintensive disorders of pregnancy (particularly preeclampsia), fetal growth restriction (reflected by low birth weight) and preterm birth, while preconception exposure has been associated with indicators relevant to ovarian function and ART performance,” Fang and her team write in the review.

As a result of widespread use and exposure, nearly all people living in the United States have detectable levels of PFAS in their blood, according to the Centers for Disease Control and Prevention, which has been measuring PFAS blood levels in the United States since 1999 through the National Health and Nutrition Examination Survey.

PFAS in reproductive tissues

PFAS are widely regarded as endocrine disrupters, the review states.

This may lead to premature ovarian insufficiency, which is when the ovaries stop working correctly before the age of 40. The potential cause of this is PFAS entering the ovaries and attacking the granulosa cells, which are the support cells that keep eggs alive.

PFAS can also change the levels of follicle-stimulating hormone, which drive egg development and maturation in females.

During pregnancy

One area that was studied was the effect of PFAS on preeclampsia risk, which is a potentially deadly pregnancy complication for both mother and child caused by the abnormal development of blood vessels in the placenta.

“Experimental evidence indicates that PFAS can inhibit endothelial tube formation and thereby compromise placental vascular development,” Fang and her team said. “Inadequate placental perfusion and endothelial dysfunction provide a coherent pathway linking placental vascular impairment with maternal vasoconstriction and hypertension, with downstream multi-organ involvement characteristic of severe HDP.”

Mood may also be affected, with proposed causes including PFAS, which causes low-grade systematic inflammation and changes the brain's response to stress.

“Therefore, incorporating psychological outcomes into PFAS risk assessment improves outcome coverage beyond somatic endpoints and better reflects the full maternal health burden.”

Looking to the future

To improve reproductive outcomes in a world where PFAS are present, the authors suggest a combination of policy changes and adjustments to the way these toxicity studies are designed.

Specifically, they suggest future studies on PFAS should incorporate exposures to other environmental factors such as microplastics to mimic “real-world exposure” because people are often exposed to many sources at once.

They also suggest studying the results of PFAS exposure on male reproduction as well as family-based designs to evaluate potential intergenerational susceptibility.

As for policies, the authors say there is a need for greater transparency about what potential PFAS products may contain, confirmed by premarket testing. This is particularly important for PFAS alternatives like hexafluoropropylene oxide dimer acid and its ammonium salt, referred to as “GenX chemicals," introduced around 2010 and advertised as a “safer” choice for manufacturers, compared with PFAS. However, these GenX chemicals have been found to have similar persistence to PFAS in terms of environmental contamination.