Abstract

If genetics defines the inheritance of DNA, epigenetics aims to regulate and make it adaptable. Epigenetic alterations include DNA methylation, chromatin remodelling, post-translational modifications of histone proteins and activity of non-coding RNAs. Several studies, especially in animal models, have reported transgenerational inheritance of epigenetic marks. However, evidence of transgenerational inheritance in humans via germline in the absence of any direct exposure to the driving external stimulus remains controversial. Most of the epimutations exist in relation with genetic variants. The present review looks at intergenerational and transgenerational inheritance in humans, (both father and mother) in response to diet, exposure to chemicals, stress, exercise, and disease status. If not transgenerational, at least intergenerational human studies could help to understand early processes of inheritance. In humans, female and male germline development follow separate paths of epigenetic events and both oocyte and sperm possess their own unique epigenomes. While DNA methylation alterations are reset during epigenetic reprogramming, non-coding RNAs via human sperm provide evidence of being reliable carriers for transgenerational inheritance. Human studies reveal that one mechanism of epigenetic inheritance cannot be applied to the complete human genome. Multiple factors including time, type, and tissue of exposure determine if the modified epigenetic mark could be transmissible and till which generation. Population-specific differences should also be taken into consideration while associating inheritance to an environmental exposure. A longitudinal study targeting one environmental factor, but different population groups should be conducted at a specific geographical location to pinpoint heritable epigenetic changes.

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