The Weismann barrier has long been regarded as a basic tenet of biology. However, upon close examination of its historical origins and August Weismann’s own writings, questions arise as to whether such a status is warranted. As scientific research has advanced, the persistence of the concept of the barrier has left us with the same dichotomies Weismann contended with over 100 years ago: germ or soma, gene or environment, hard or soft inheritance. These dichotomies distract from the more important questions we need to address going forward. In this review, we will examine the theories that have shaped Weismann’s thinking, how the concept of the Weismann barrier emerged, and the limitations that it carries. We will contrast the principles underlying the barrier with recent and less recent findings in developmental biology and transgenerational epigenetic inheritance that have profoundly eroded the oppositional view of germline vs. soma. Discarding the barrier allows us to examine the interactive processes and their response to environmental context that generate germ cells in the first place, determine the entirety of what is inherited through them, and set the trajectory for the health status of the progeny they bear.

Multiple lines of evidence suggest that exposure to per- and polyfluoroalkyl substances (PFAS) may alter glucose homeostasis, particularly during pregnancy, and may affect risk for developing gestational diabetes mellitus (GDM). While previous systematic reviews have been conducted on this topic, they did not assess internal validity of the included studies and their search strategies were narrowly focused. The objective of this study is to assess the effect of higher PFAS exposure (defined by individual compounds or mixtures measured before or during pregnancy) on GDM and subclinical measures of impaired glucose homeostasis (measured during pregnancy) compared to lower PFAS exposure in pregnant. We developed our systematic review protocol in accordance with the Navigation Guide. Peer-reviewed journal and grey literature searches were piloted in to identify relevant studies and refine our search terms and strategy. We also piloted the study screening criteria and data extraction form in DistillerSR, and refined our protocol accordingly. The risk of bias assessment protocol was adapted from Navigation Guide guidance and will be piloted and performed in DistillerSR. Pending the identification of comparable studies, quantitative meta-analyses will be performed where possible. Study results that cannot be quantitatively synthesized will be included in a narrative synthesis. The quality and strength of the body of evidence will be evaluated using Navigation Guide methodology, which is informed by guidance from the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation (GRADE). We also made refinements to the quality of evidence considerations based on guidance from the National Institute of Environmental Health Sciences (NIEHS) Office of Health Assessment and Translation (OHAT). This work was supported by the Systematizing Data on Per- and Polyfluoroalkyl Substances and Health Northeastern University TIER 1 Award.

All the cells in our bodies are derived from the germ cells of our parents, just as our own germ cells become the bodies of our children. The integrity of the genetic information inherited from these germ cells is of paramount importance in establishing the health of each generation and perpetuating our species into the future. There is a large and growing body of evidence strongly suggesting the existence of substances that may threaten this integrity by acting as human germ cell mutagens. However, there generally are no absolute regulatory requirements to test agents for germ cell effects. In addition, the current regulatory testing paradigms do not evaluate the impacts of epigenetically mediated intergenerational effects, and there is no regulatory framework to apply new and emerging tests in regulatory decision making. At the 50th annual meeting of the Environmental Mutagenesis and Genomics Society held in Washington, DC, in September 2019, a workshop took place that examined the heritable effects of hazardous exposures to germ cells, using tobacco smoke as the example hazard. This synopsis provides a summary of areas of concern regarding heritable hazards from tobacco smoke exposures identified at the workshop and the value of the Clean Sheet framework in organizing information to address knowledge and testing gaps.

Drinking water is a major source of per- and polyfluoroalkyl substance (PFAS) exposure in contaminated communities. Even after mitigation, residents may still have elevated serum PFAS levels; however, duration of elevated body burdens and influence of drinking water type (unfiltered tap, filtered tap, bottled) are poorly characterized. Evaluate associations of residential history and drinking water type with serum PFAS among individuals living in communities with historical drinking water contamination. The Massachusetts (MA) PFAS & Your Health Study is part of the PFAS Multi-site Study, a cross-sectional epidemiological study in eight U.S. states. In 2021-2023, we collected blood and questionnaire data from 673 adults in Hyannis and Ayer, MA, where public water systems were historically contaminated by PFAS mainly from aqueous film-forming foam (AFFF). We analyzed residential histories for 399 participants and calculated time lived in these communities between 2000 and major PFAS mitigation by public water supplies in 2016 (Hyannis) and 2018 (Ayer). We used multivariable linear regression to examine associations of time lived in study area and drinking water type with serum perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA), controlling for age and sex. Median serum PFOS and PFHxS concentrations were 2.1-2.8 times higher in Hyannis than Ayer, consistent with higher historical PFAS concentrations in Hyannis water. In both communities, time lived in study area was associated with higher serum PFOS and PFHxS. In Hyannis, long-term residents ( > 16 years) had 2.3 times higher PFHxS and 1.4 times higher PFOS than short-term residents ( < 5 years). Filtered tap or bottled water was associated with lower serum PFAS compared to unfiltered tap water in Hyannis but not in Ayer. Actions to reduce exposures from drinking water in contaminated communities can lead to lower serum PFAS levels years later. PFAS exposure from drinking water affects millions of U.S. residents. In this cross-sectional study, we found that residents of communities with contaminated drinking water had elevated serum PFAS levels, particularly long-term residents, even when mitigation of PFAS in public water supplies occurred years prior. Additionally, we found that exposure reductions from drinking filtered tap or bottled water, compared to unfiltered tap water, were reflected in serum PFAS levels. Our findings suggest that addressing PFAS exposures from drinking water, both at the municipal and household level, may reduce cumulative PFAS body burden and thus reduce risk of related health effects.