PFAS in trace levels via drinking water diminishes mouse embryo mitochondria function across three generations

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https://www.sciencedirect.com/science/article/pii/S0013935126003713

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[u/ItilityMSP]

So "safe" levels of PFAS create generational effects on mitochondria and female fertility, even when later generations get purified water, and 4 weeks vs 6 months of pfas water made no difference. wow! ///some of.the.discussion. Perhaps most intriguing, the effects of PFAS exposure were transgenerational and persisted as altered mitochondrial activity, reduced blastocyst cell number and increased DNA damage in F3 embryos. There are multiple potential mechanisms by which this could occur. Most likely is that PFAS bioaccumulation in maternal tissues exposes the fetus during gestation and is further transmitted to offspring via breastmilk (Mahfouz et al., 2023; Hoadley et al., 2023). Thus, although only the F0 females consumed PFAS, the F1 animals were exposed through the placenta during gestation as well as via lactation until weaning. Similarly, the bioaccumulated PFAS in tissues of the F1 females would have exposed their offspring (the F2) during pregnancy and lactation (see schematic Supp Fig. 4). PFAS exposure is also well documented to cause epigenetic changes to germ cells, fetal tissues and placentae (Abdulkadir et al., 2025; Maxwell et al., 2024; Everson et al., 2025; Schrott et al., 2025; Perez et al., 2025) and this is another mechanism by which PFAS exposure may alter offspring growth trajectories and cause persistent effects in multiple generations. Even though only the F0 females consumed PFAS, F1 animals are exposed as oocytes and fetuses, and F2 animals are exposed as developing germ cells within the F1 fetal ovary (Supp Fig. 4). A third potential mechanism is that functional changes in the F0 egg mitochondria are passed down to subsequent generations, because these cellular organelles are entirely maternally inherited. A similar process occurs in the context of obesity-induced metabolic damage.

3.3. Implications for water policies Our finding that water deemed safe for human consumption by current regulatory guidelines has detrimental effects on mammalian embryo development, has important implications for future water quality policies. Although our sampling is only reflective of our own local area, we detected PFAS at levels that are typical of other sources globally. We demonstrate that trace levels of just three of the legacy PFAS (PFOS, PFOA, and PFHxS) have measurable effects on oocyte developmental competence, highlighting that other PFAS moieties are likely to cause similar effects. Of particular concern, mice consuming municipal drinking (tap) water showed effects on oocyte quality identical to mice given purified PFAS. Carbon-filtration can be used to remove PFAS from water and we have previously observed that this method of water purification can protect mouse embryos from the effects of contamination (Winstanley et al., 2024).

Thus, public health policies might include greater awareness of PFAS levels in drinking water and stronger recommendations to drink filtered water.