Paternal exposures had their moment to shine during the 2024 Symposium Session “It Takes Two! Paternal Exposures and Their Impacts on Offspring Health.” As someone who has studied reproductive and developmental toxicity primarily through the mother, it was great to be reminded that it is not just the maternal exposure that matters when it comes to offspring health—even in the case of environmental exposures! During this session, a diverse array of speakers provided their perspectives on how paternal exposures (like to cannabis or wildfire smoke) can later affect offspring.
Mechanisms for how paternal exposure can affect offspring center on epigenetic mechanisms (e.g., DNA methylation, post-translational modifications of histones, and noncoding RNAs). In sum, altering the sperm epigenome leads to marks that are retained on the sperm, transmitted via fertilization, and persist during subsequent fetal development and embryonic gene expression. The sperm epigenome can thus impact fertility, fetal development, and offspring health.
Sarah Kimmins, PhD, McGill University, opened the session’s talks with an introduction on paternal environmental exposures and their influence on development via the sperm epigenome. Dr. Kimmins gave an early example from a Swedish population, which demonstrated that an overabundance of food for grandfathers was associated with increased diabetes risk later in their grandchildren. She also gave an example from her lab’s extensive work studying the paternal effects of the pesticide DDT. Paternal DDT exposure in two unique human populations led to similar genomic changes in neurodevelopment genes, and these changes were retained in the later embryo, implicating DDT alteration of the sperm epigenome in the paternal origins of adult health and disease.
Next, Luke Montrose, PhD, Colorado State University, spoke on aberrant sperm DNA methylation following wildfire smoke exposure in mice and in humans. Exposure to wildfire smoke in mice led to alterations in the sperm epigenome, specifically changes to DNA methylation. Similarly, in a human study of wildland firefighters, sperm from men before and during a wildfire season showed that sperm DNA methylation was altered following exposure to wildfire smoke. Both mice and humans showed similar methylation changes in paternally imprinted genes.
Ed Levin, PhD, Duke University, followed with a talk on paternal preconception exposure to delta-9-THC or cannabis extract and its impact on sperm DNA methylation and offspring neurobehavioral function. Dr. Levin showed that periconceptional exposure to THC in fathers changes the methylation patterns of sperm DNA and also changes DNA methylation patterns in the offsprings’ brains. Ultimately, paternal exposure to THC in rodents led to deficits in learning and memory for the offspring and even led to neurodevelopment impairment in the F2 generation, with the F2 offspring demonstrating delayed reflex development.
Qi Chen, MD, PhD, University of Utah, spoke on sperm RNA-mediated epigenetic inheritance and the emerging tools to study small RNAs and RNA modifications. Sperm RNA (including tsRNAs, miRNAs, rsRNAs, and lncRNAs) is a broad and functionally diverse group of molecules, and tools like PANDORA-seq are helping us better understand the contribution of fathers to the health of their offspring. Another tool, MLC-Seq, is a mass spectrometry–based approach for directly sequencing tRNA or tsRNAs. As these tools develop further, we’ll likely gather increasing evidence for the importance of sperm RNA modifications for offspring health.
Colette Miller, PhD, US EPA, concluded the Symposium talks by presenting on the impact of biomass smoke exposure during sperm maturation on the health of both the father and their offspring. Her lab has developed a rat model of eucalyptus smoke exposure that can represent wildfire smoke exposures in Southern California and Australia. In the rat model, repeated exposure to smoke during the period of sperm maturation impaired sperm motility and altered non-coding RNA in the caudal sperm.
Toward the end of the Symposium, Dr. Miller alluded to the fact that nearly all the talks focused on smoke exposure, pointing out there are many more avenues open for studying paternal exposure: “We didn’t necessarily mean to focus this all on smoke exposures, but that really, in my mind, just means we need more of you guys in this room to start studying paternal exposure effects.”
Currently, the scarcity of studies means that chemical risk assessment can’t factor in the father—ignoring the contribution of paternal exposures and potentially overrepresenting the causal primacy of maternal effects. With improving tools and increased interest, I’m hopeful that we’ll improve our understanding and appreciation for the role of paternal stressors in developmental toxicology.
This blog reports on the Symposium Session titled “It Takes Two! Paternal Exposures and Their Impacts on Offspring Health” that was held during the 2024 SOT Annual Meeting and ToxExpo. An on-demand recording of this session is available for meeting registrants on the SOT Online Planner and SOT Event App.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email SOT Headquarters.
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