Sex-specific cellular and molecular mechanisms of PFAS-induced reproductive toxicity.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing in vitro, in vivo, and epidemiological mechanistic literature.
PubMed 42379283 · doi:10.1016/j.tox.2026.154535
What was done
Narrative review synthesizing in vitro, in vivo, and epidemiological evidence examining the cellular and molecular mechanisms of reproductive toxicity associated with exposure to legacy and replacement per- and polyfluoroalkyl substances (PFAS) across sexes.
What was found
The abstract reports no quantitative data or effect sizes. It identifies shared toxicity pathways across sexes—including oxidative stress, mitochondrial dysfunction, endocrine perturbation, inflammation, epigenetic modifications, and dysregulated cell survival. It also details sex-specific pathways: disruption of the blood-testis barrier, steroidogenesis, germ cell apoptosis, and spermatogenesis in males; impairment of folliculogenesis, oocyte maturation, hormone biosynthesis, and granulosa/cumulus cell function in females; and placental dysfunction with developmental programming risks during pregnancy.
Why it matters
Synthesizing sex-specific cellular pathways clarifies distinct biological vulnerabilities to persistent environmental toxicants, informing reproductive health risk assessments for both legacy and newer replacement PFAS.
Limits
As a narrative review, it lacks systematic search methodology, quality assessment of included papers, or quantitative meta-analytic pooling. Specific exposure thresholds, effect magnitudes, human-to-animal translation discrepancies, and the number of underlying studies are not detailed in the abstract.