Role of miRNA in the Transmission of Metabolic Diseases Associated With Paternal Diet-Induced Obesity

The concept of Developmental Origins of Health and Diseases (DOHaD) recognizes that an unfavorable maternal environment alters the developmental trajectory of the fetus and can lead to long-term risk of developing chronic noncommunicable diseases. More recently, the concept of a paternal transmission [Paternal Origins of Health and Diseases (POHaD)] has emerged stressing the impact of paternal overweight or obesity on offspring's health and development. While very few examples of paternal epigenetic inheritance of metabolic disorders have been evidenced in human, many experimental mouse models based on high-fat diet (HFD)-induced paternal obesity have been developed to breakdown molecular mechanisms involved in the process. Besides DNA methylation and chromatin structure, sperm short noncoding RNAs have been considered as the main epigenetic vector of inheritance of paternally environmentally induced changes. Among them, sperm miRNAs are one particular subspecies sensitive to environmental changes and obesity can modify the sperm miRNA profile. Once delivered into the zygote, these molecules might induce epigenetic modifications in the embryo, thereby leading to consequences for fetus development and offspring physical and metabolic health later on in life. Furthermore, some data also suggest that metabolic pathologies may be intergenerationally or transgenerationally transmitted.