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

Tom P Fleming1, Congshan Sun2,3, Oleg Denisenko4

  • 1Biological Sciences, Southampton General Hospital, University of Southampton, Southampton SO16 6YD, UK.

International Journal of Environmental Research and Public Health
|September 10, 2021
PubMed
Summary
This summary is machine-generated.

Maternal nutrition around conception impacts offspring health via epigenetics. Early embryo development is programmed for survival, but this can increase chronic disease risk later in life.

Keywords:
DOHaDblastocystlow protein dietmTORC1maternal undernutritionperi-conceptionprimitive endodermribosome biogenesistrophectodermuterine fluid

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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.