Origins of Lifetime Health Around the Time of Conception: Causes and Consequences

Abstract

Parental environmental factors including diet, body composition, metabolism and stress affect the health and chronic disease risk of people throughout their lives, as captured in the 'Developmental Origins of Health and Disease' (DOHaD) concept. Research across epidemiological, clinical and basic science fields has identified the period around conception as being critical in the processes mediating parental influences on the next generation's health. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune and neurological morbidities, often termed 'developmental programming'. We review 'periconceptional' induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and from the use of assisted reproductive treatment. Human studies and animal models demonstrate the underlying biological mechanisms, including epigenetic, cellular, physiological and metabolic processes. A novel meta-analysis of mouse paternal and maternal protein undernutrition indicate distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model

“…Despite the hyperinsulinemia and hypertriglyceridemia exhibited by fetuses of R021 group, that may increase the susceptibility to fatty liver, type 2 diabetes, and obesity during adulthood [22], in the present work the studied offspring did not exhibit any remarkable alteration in growth and food consumption during juvenile phase until puberty. These results agree with those of Symmeon et al [74], who reported similar body weight and feed intake during fattening in rabbit offspring of undernourished dams and, with Hyatt et al [10] in juvenile sheep undernourished during early to mid-gestation.…”

“…Compromised growth of a fetus in the uterus can induce a plethora of dysfunction of organs (kidney, liver, mammary gland, muscle, pancreas, and placenta) and/or organ systems (cardiovascular, adipose, nervous, endocrine, gastrointestinal, immune, and reproductive system). This situation is associated with a high prevalence of chronic diseases in later life [22], such as type 2 diabetes, obesity, cardiovascular disease, etc. [23,24], which has been considered as a global epidemic [25].…”

The influence of seminal plasma on offspring development and health

“…Similar changes in uterine phenotype and offspring development have been observed in response to maternal low protein diet fed exclusively during preimplantation development [40][41][42][43]. Interestingly, comparisons between maternal and paternal periconceptional low protein diet on the magnitude of offspring programming revealed similar size effects between parents [2].…”

“…In 1989, David Barker published a study linking impaired growth in utero with blood pressure at the age of 10 and increased adult mortality risk for cardiovascular disease in humans [1]. In the decades that have followed, a wealth of human epidemiological data and animal model studies have established that the quality and quantity of a mothers diet during pregnancy can influence the development, growth and long-term cardiovascular and metabolic health of her offspring [2]. Out of this large body of multidisciplinary data, the Developmental Origins of Health and Disease (DOHaD) concept [3] has been developed to understand how environmental conditions experienced during gamete maturation, embryo development and fetal growth can affect offspring long-term health.…”

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

“…However, it is now clear that exposure to different environments before birth plays a significant role in the origin of these diseases. Scientists are now increasingly focusing on the understanding of the hypothesis known as the Developmental Origins of Health and Disease (DOHaD) [1,2]. The DOHaD hypothesis has significant implications for understanding the epidemiology of non-communicable diseases (NCDs), especially those including the onset of cardiovascular, metabolic and neurological disorders [3,4].…”