Project description
Investigating the potential male reproductive toxicity of DBP
Does paternal epigenetic inheritance affect offspring through epigenetic inheritance? Do male life experiences, such as adult exposure to the anti-androgenic model substance and environmental pollutant di-n-butyl phthalate (DBP), affect offspring? The answers to such questions may have important public health implications. Some studies have shown that DBP has potential testicular toxicity. The EU-funded PATER project will explore this subject by researching paternal epigenetic inheritance and how this occurs in mammals. By linking animal experimental data about paternal transmission to human studies, PATER will determine a causal connection between environmentally induced biomolecular alterations in sperm and offspring phenotype. To date, the effects of adult anti-androgen exposure on the sperm epigenome and offspring phenotype have been scarcely studied.
Objective
Epigenetic inheritance may not only occur in plants and fungi but also in mammals. While the effect of maternal lifestyle and in utero exposures is well studied, paternal epigenetic inheritance is a novel research field, especially in regard to chemical exposures. Many environmental pollutants exhibit anti-androgenic function. Despite the vital role of androgens in spermatogenesis, the effects of adult anti-androgen exposure on the sperm epigenome and offspring phenotype have been scarcely studied.
The overall aim of this novel project is to increase the understanding of if, and how, male life experiences such as adult exposure to the anti-androgenic model substance and pollutant DBP (di-n-butyl phthalate) may affect offspring through paternal epigenetic inheritance. I accomplish this by integrating animal and human studies, using RNA-sequencing and mass spectrometry-based peptidomics to identify DBP-induced alterations in the sperm transcriptome and peptidome, examine noncoding RNAs and peptides role in embryogenesis, development and long-term health of the offspring in two generations. To validate the mechanistic importance of the sperm molecular alterations microinjections of selected biomolecules into zygotes will be conducted. This is the first project to investigate multigenerational effects of adult male exposure to anti-androgens in detail, and investigate the role of the sperm peptidome in paternal epigenetic inheritance. Directly linking animal experimental data about paternal transmission to human studies is unique and necessary to determine causal connection between environmentally-induced biomolecular alterations in sperm and offspring phenotype. The project can contribute to ground-breaking mechanistic understanding of how male life experiences may affect offspring through epigenetic inheritance. The findings may also have important public health implications via new regulations of anti-androgenic chemicals and male preconceptional interventions.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2018-STG
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10691 Stockholm
Sweden
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