Abstract
Numerous studies in humans and in animal models have demonstrated that exposure to adverse environmental conditions in early life results in long-term structural and functional changes in an organism, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life. Such effects are not limited to the first generation offspring but may be transmitted to a second or a number of subsequent generations, through non-genomic mechanisms. While the transmission of ‘programmed’ effects through the maternal line could occur as a consequence of multiple influences, for example, altered maternal physiology, the inheritance of effects through the male line is more difficult to explain and there is much interest in a potential role for transgenerational epigenetic inheritance. In this review, we will discuss the mechanisms by which induced effects may be transmitted through the paternal lineage, with a particular focus on the role of epigenetic inheritance.This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.
Highlights
Numerous studies in humans and in animal models have demonstrated that development is highly regulated, embryos remain sensitive to environmental cues, and exposure to adverse environmental conditions may result in long-term structural and functional changes, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life [1]
Epigenetic reprogramming occurs during two distinct developmental phases [32]: first, DNA methylation in primordial germ cells (PGCs) is erased during early development in both males and females following the migration of PGCs into the genital ridge [33]
Cytosine methylation (5-methylcytosine, 5mC) at CpG dinucleotides occurs through the actions of the DNA methyltransferases (Dnmts). 5mC is important in the regulation of gene expression, in the maintenance of transcriptional silencing, and it is found at heterochromatic regions of the genome and over repetitive elements. 5mC is important in the silencing of retrotransposons and endogenous retroviral sequences, in the phenomenon of genomic imprinting and in the inactivation of the X-chromosome
Summary
Numerous studies in humans and in animal models have demonstrated that development is highly regulated, embryos remain sensitive to environmental cues, and exposure to adverse environmental conditions may result in long-term structural and functional changes, increasing the risk of cardiometabolic, neurobehavioural and reproductive disorders in later life [1]. These ideas have led to the rapid growth of the Developmental Origins of Health and Disease (DOHaD) field. We will discuss potential mechanisms by which induced effects may be transmitted through the paternal lineage, with a particular focus on the role of epigenetic inheritance
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