Emerging evidence suggests that exposures in pre-puberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father's exposed to tobacco smoking or overweight that started in pre-puberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of pre-puberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during pre-puberty play a role for grand-offspring health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multi-generation data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male pre-puberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research and biological plausibility, all support the notion that exposures in the pre-puberty of males may influence the phenotype of future offspring.

Exposures during the prepuberty period and future offspring's health: evidence from human cohort studies

Accordini, Simone;
2021

Abstract

Emerging evidence suggests that exposures in pre-puberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father's exposed to tobacco smoking or overweight that started in pre-puberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of pre-puberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during pre-puberty play a role for grand-offspring health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multi-generation data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male pre-puberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research and biological plausibility, all support the notion that exposures in the pre-puberty of males may influence the phenotype of future offspring.
Adolescence; Allergies; Anthropometry; Asthma; Father’s overweight; Father’s smoking; Nongenetic heredity; Obesity; Prepuberty; Puberty; RHINESSA; Sex-specific
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/1047744
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