Perinatal origin of adult diseases

Abstract

Three relevant, interrelated scientific advances are described: the concept of critical periods (CPs), the Barker Hypothesis (BH), and the underlying epigentic mechanisms involved. Critical periods are genetically programmed, highly sensitive time intervals during which the interaction between environment and individuals generates the development of physiological processes related to physical growth and development, survival (breastfeeding), social behavior, and learning. Barker hypothesis is based on the finding that prenatal malnutrition (for example, lowbirthweight) is closely related to mortality due to cardiovascular disease CVD) in the adult, and to the risk conditions leading to it: insuline resistence, metabolic syndrome, obesity, and high blood pressure. This association is no due to genetical causes, but secondary to nutritional deficits which in turn generate epigenetic mechanisms of methylation of DNA basis and cromatine proteines (histones), which do not modify the genetic code but modulate its expresion, reinforcing some genes, inhibiting others, regulating when and where they are expressed. These genes participate in the process called programming, consisting of permanent changes in the response to stimulation of metabolic and hormone regulators, such as, for example, increasing insuline resistence. Epigenetic changes persist even when original conditions (fetal or perinatal malnutrition) are no longer present. This, in turn, affects health of the offspring later in adult life, creating thus the same environmental prenatal conditions to the next generation. This transgenerational effects of early nutritional experiences are more frequent in population groups of por socioeconomic level, and consequently have serious implications in the future health of Latin American populations.

Transgenerational Effect of Early Childhood Famine Exposure in the Cohort of Leningrad Siege Survivors’ Offspring

“…It is known that most human organs have a critical development period at the prenatal stage. In the case of serious nutritional deficiency, the number of functioning glomeruli decreases, leading to increased filtration load, increased GFR throughout postnatal life, and subsequent damage to functioning glomeruli (18). Reports on the Northern China famine cohort study also presented significantly lower calculated GFR in prenatally exposed participants to starvation and their children compared to controls.…”

“…This may be due to transgenerational changes in the epigenome through the programming of nephron deficiency in germ cells (4). In the long term, renal filtration capacity can cause glomerulosclerosis, and finally hypertension in adulthood (18).…”

Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders

“…Moreover, the fetal basis of adult disease hypothesis introduced the concept that adult health and behavior are programmed in utero and shaped throughout life by exposure to new and previously experienced stressors via epigenetic mechanisms ( Barker et al, 1993 ; Calkins and Devaskar, 2011 ; Argyraki et al, 2019 ). Epigenetic mechanisms are changes in DNA methylation and histone modification, which do not modify the genetic code but modulate transcription and translation, reinforcing or inhibiting some genes, and regulate when and where corresponding proteins are expressed ( Lejarraga, 2019 ). These genes alter programming, thereby modifying responses following stimulation of metabolic and hormone regulators.…”

“…For example, prenatal exposure may contribute to health problems that arise later in life such as obesity, diabetes, cardiovascular disease, cancer, and PD. Epigenetic changes persist even when the original triggering conditions are no longer present ( Ho and Tang, 2007 ; Lejarraga, 2019 ). In line with this, juvenile and early life stresses have been linked to long term meta-plasticity-like effects on inflammatory responses in adulthood, and this memory may increase susceptibility to neurodegenerative diseases in adult life ( Shtoots et al, 2018 ).…”

Comparison of dipsogenic responses of adult offspring as a function of different perinatal programming models

“…Gestational characteristics modify the intrauterine environment and differentially program the developing organism. Studies carried out in the last decades of the 20th century have provided evidence of the important role of the environment when it acts during critical periods of the intrauterine and/or early postnatal life (Lejarraga, 2019). Hence, a widely recognized hypothesis that considers the environmental influence on the new individual and its long-term effects is the "fetal origin hypothesis", postulated by Barker in the 1990s (Barker, 2002;Barker et al, 2002;de Boo & Harding, 2006).…”