Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk

Area of Science:

• Developmental biology
• Epigenetics
• Reproductive health

Background:

• The environment around conception significantly influences developmental programming.
• This programming has lasting effects on health and disease risk throughout life.
• The Developmental Origins of Health and Disease (DOHaD) concept highlights the importance of peri-conception exposures.

Purpose of the Study:

• To review the effects of maternal undernutrition during the peri-conception period.
• To examine human data and a mouse model of protein restriction.
• To explore the mechanisms linking peri-conception nutrition to long-term health outcomes.

Main Methods:

• Analysis of human datasets on peri-conception macronutrient deprivation.
• Utilizing a mouse model with maternal low protein diet during the peri-conception period.
• Investigating molecular and physiological changes in extra-embryonic and embryonic tissues.

Main Results:

• Maternal undernutrition around conception alters the epigenome, affecting cardiometabolic and neurological health.
• The mouse model shows a stepwise progression of altered developmental programming due to maternal metabolite deficiency.
• This leads to growth trajectory maladaptation and increased chronic disease comorbidities.

Conclusions:

• Early embryos actively sense their environment to optimize development for survival, potentially at the cost of later disease.
• Peri-conception nutrition influences a complex interplay of nutrient sensing, signaling, epigenetic, and metabolic pathways.
• Adverse peri-conception exposures, including overnutrition and ART, underscore the need for preconception health interventions.