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

Area of Science:

• Environmental Epigenetics
• Reproductive Biology
• Developmental Origins of Health and Disease

Background:

• Emerging evidence suggests paternal exposures before conception can influence offspring phenotype.
• Prepubertal exposures, specifically in males, are increasingly recognized as potentially impactful.
• Multigenerational studies face challenges due to data complexity and deficiencies.

Purpose of the Study:

• To investigate the impact of paternal prepubertal exposures on offspring health outcomes.
• To explore the role of male prepuberty as a sensitive window for environmental influences.
• To synthesize epidemiological and mechanistic evidence supporting intergenerational effects.

Main Methods:

• Analysis of large human cohorts (RHINESSA, ALSPAC) examining paternal prepubertal exposures (smoking, overweight) and offspring health.
• Review of experimental models demonstrating sperm small RNA involvement in transmitting paternal exposures.
• Statistical analyses accounting for complexities in human multigeneration data.

Main Results:

• Offspring of fathers with prepubertal smoking or overweight showed poorer respiratory health (asthma, lower lung function).
• Prepubertal smoking in fathers was linked to increased offspring fat mass.
• Experimental models confirmed that paternal smoking affects offspring weight and sperm small RNA profiles.

Conclusions:

• Paternal prepubertal exposures, including smoking and overweight, significantly influence offspring phenotype, particularly respiratory health and adiposity.
• Sperm small RNAs are a plausible mechanism for transmitting paternal environmental exposures to offspring.
• Male prepuberty represents a critical developmental window for epigenetic reprogramming, making it susceptible to environmental impacts that affect future generations.