Abstract
Environment around conception can influence the developmental programme with lasting effects on gestational and postnatal phenotype and with consequences for adult health and disease risk. Peri-conception exposure comprises a crucial part of the ‘Developmental Origins of Health and Disease’ (DOHaD) concept. In this review, we consider the effects of maternal undernutrition experienced during the peri-conception period in select human models and in a mouse experimental model of protein restriction. Human datasets indicate that macronutrient deprivation around conception affect the epigenome, with enduring effects on cardiometabolic and neurological health. The mouse model, comprising maternal low protein diet exclusively during the peri-conception period, has revealed a stepwise progression in altered developmental programming following induction through maternal metabolite deficiency. This progression includes differential effects in extra-embryonic and embryonic cell lineages and tissues, leading to maladaptation in the growth trajectory and increased chronic disease comorbidities. The timeline embraces an array of mechanisms across nutrient sensing and signalling, cellular, metabolic, epigenetic and physiological processes with a coordinating role for mTORC1 signalling proposed. Early embryos appear active participants in environmental sensing to optimise the developmental programme for survival but with the trade-off of later disease. Similar adverse health outcomes may derive from other peri-conception environmental experiences, including maternal overnutrition, micronutrient availability, pollutant exposure and assisted reproductive treatments (ART) and support the need for preconception health before pregnancy.
Highlights
The period around conception is recognised as the key transition between generations and a vulnerable time in our gestation to adverse environmental influences.These can alter the course of development and impose lasting effects on health through life.By environment, a wide range of external influences are relevant, including the quality ofInt
We consider how nutritional quality may interface with the early embryo and how the embryo may respond in ways that persist beyond the peri-conception period, involving diverse cell lineages and multiple mechanisms, and representing a stepwise progression from altered cellular homeostasis to adult maladaptation and disease risk
We show that of the three branched-chain AAs (BCAAs), isoleucine deficiency is the most potent activator of TE histotrophic nutrition mediated through nuclear translocation of the transcription factor TFEB to drive lysosome biogenesis [65]
Summary
The period around conception is recognised as the key transition between generations and a vulnerable time in our gestation to adverse environmental influences These can alter the course of development and impose lasting effects on health through life. We consider how nutritional quality may interface with the early embryo and how the embryo may respond in ways that persist beyond the peri-conception period, involving diverse cell lineages and multiple mechanisms, and representing a stepwise progression from altered cellular homeostasis to adult maladaptation and disease risk. In this context, we propose a key role for nutritional signalling pathways in coordinating longterm consequences. We evaluate how these biological processes impact on policy for maternal intervention in pregnancy and the case for preconception care to promote offspring health
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