Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice

Area of Science:

• Reproductive biology
• Epigenetics
• Developmental biology

Background:

• The Developmental Origins of Health and Disease (DOHaD) hypothesis explores links between early-life conditions and adult health.
• Mechanisms connecting paternal diet to offspring health are not well understood.

Purpose of the Study:

• To investigate the impact of a paternal low-protein diet (LPD) on male mouse reproductive health and offspring development.
• To elucidate the specific roles of sperm epigenetics and seminal plasma in mediating paternal dietary effects.

Main Methods:

• Developed a mouse model with paternal low-protein diet (LPD) versus normal protein diet (NPD).
• Analyzed sperm epigenetics (global hypomethylation) and testicular gene expression.
• Assessed maternal uterine responses and offspring health outcomes (metabolic, hepatic, gut microbiota).
• Utilized artificial insemination and vasectomized male mating to separate sperm and seminal plasma effects.

Main Results:

• Paternal LPD induced global sperm hypomethylation and altered testicular gene expression.
• Females mated with LPD males showed impaired uterine responses.
• Offspring conceived from LPD sperm and/or seminal plasma exhibited increased adiposity, glucose intolerance, nonalcoholic fatty liver disease markers, and altered gut bacteria.

Conclusions:

• Paternal diet influences offspring health through both sperm epigenetic modifications and seminal plasma-mediated effects on the maternal environment.
• These findings provide insights into the programming mechanisms linking paternal nutrition to long-term offspring health outcomes.