SeriesOrigins of lifetime health around the time of conception: causes and consequences
Introduction
The notion that maternal physiology, body composition, diet, and lifestyle during pregnancy have profound and enduring effects on the long-term health of the offspring, and disease risk into adulthood, has received strong evidential support across the epidemiological, medical, and basic science fields.1, 2, 3 Thus, the Developmental Origins of Health and Disease concept has emerged,3 suggesting that poor developmental experience can increase the risk of non-communicable diseases in later life, including cardiovascular and metabolic comorbidities (such as hypertension, obesity, and type 2 diabetes), atopic conditions, cancer, and neurological impairment. Research into the concept has focused on the time during pregnancy when the conceptus is most vulnerable to adverse influences, thereby informing targeted protection and possible intervention. Increasing evidence points to the importance of the time around conception, known as the periconceptional period.
This Series paper focuses on four broad periconceptional environmental exposures shown to adversely affect humans and animal models (figure 1), and discusses mechanistic causes and consequences. We also report a meta-analysis on the relative contributions of maternal and paternal factors on long-term periconceptional influences, in an established low protein diet model of parental undernutrition.
Section snippets
Periconceptional developmental conditioning
The periconceptional period has been variously defined, but for the Developmental Origins of Health and Disease concept the key events broadly cover the completion of meiotic maturation of oocytes, differentiation of spermatozoa, fertilisation, and resumption of mitotic cell cycles in the zygote, marking the transition from the parental to the embryonic genome,4 and the onset of morphogenesis up to implantation.5 This process represents a period of a few weeks, depending on the mammalian
Periconceptional developmental conditioning through maternal overnutrition and obesity
The global rise in maternal obesity is associated with reduced female fertility and heightened risk of obesity in the offspring.2 The adverse effects of high maternal body-mass index (BMI) on the offspring could reflect elevated maternal glucose and insulin concentrations, which drive fetal growth and adiposity (resulting in increased birth and childhood weight), but might also include shared life-style factors within families.8 Impaired metabolism in offspring might also be associated with
Human studies
Poor nutrition in utero and low birthweight remain highly prevalent in low-income and middle-income countries, and are associated with increased risks of chronic diseases in later life across diverse human populations, particularly if followed by accelerated weight gain during infancy.1, 3 Similar human cardiometabolic and neurological consequences arise from maternal exposure to famine, for example, the Dutch Hunger Winter of 1944–45. In human studies it is difficult to pinpoint gestational
Paternal origin of periconceptional developmental programming
Although the connection between a mother's diet and the long-term health of her offspring has been studied in detail, understanding of how a father's diet impacts his offspring remains limited. However, links are emerging between paternal lifestyle, sperm quality, and impaired offspring health.11 Here, both direct (sperm quality, epigenetic status, DNA integrity) and indirect (seminal fluid composition) paternal mechanisms have been identified; in mice these mechanisms have been shown to affect
Defining the parental contribution to periconceptional developmental effects
Shared maternal and paternal dietary and lifestyle influences could potentially combine for greater impact on periconceptional development. However, most research models to date are uniparental in design, and the combined effects of both parents are unknown. Whether the impact of poor paternal diet on offspring development and wellbeing is of equivalent importance to that of poor maternal diet is also unknown. We did a meta-analysis of our mouse maternal and paternal LPD diet models, using
Periconceptional developmental programming and assisted reproductive treatment
Direct evidence for human periconceptional effects comes from assisted reproductive treatments, during which mature gametes, and the preimplantation embryo, are exposed to precisely timed in-vitro manipulations. Several million, apparently healthy, children have now been born worldwide using assisted reproductive treatments, but relatively little is known about the possible impact of the technology-associated exposures during conception and very early development on their health status during
Diversity and commonality in periconceptional effects
The evidence reviewed previously suggests that periconceptional experience can induce lifelong changes in phenotype, affecting disease risk. Beyond these nutritional and assisted reproductive treatment conditions, studies in rodents show broad examples of periconceptional effects, such as from maternal stress.88 Moreover, maternal alcohol consumption exclusively around conception induced metabolic dysfunction in rat adult offspring with evidence of epigenetic disturbance.89 Maternal systemic
Conclusion
We propose that there is sufficient evidence from human and animal research showing that the periconceptional period is a key window during which poor maternal and paternal physiology, body composition, metabolism, and diet can induce increased risk of chronic disease in offspring—a lifetime legacy and major driver of health burden in the 21st century. The evidence that similar consequences can result from assisted reproductive treatment practices sharpens the focus on this window.
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