Embryonic and foetal development are critical periods of development in which several environmental cues determine health and disease in adulthood. Maternal conditions and an unfavourable intrauterine environment impact foetal development and may programme the offspring for increased predisposition to metabolic diseases and other chronic pathologic conditions throughout adult life. Previously, non-communicable chronic diseases were only associated with genetics and lifestyle. Now the origins of non-communicable chronic diseases are associated with earlylife adaptations that produce long-term dysfunction. Early-life environment sets the long-term health and disease risk and can span through multiple generations. Recent research in developmental programming aims at identifying the molecular mechanisms responsible for developmental programming outcomes that impact cellular physiology and trigger adulthood disease. The identification of new therapeutic targets can improve offspring's health management and prevent or overcome adverse consequences of foetal programming. This review summarizes recent biomedical discoveries in the Developmental Origins of Health and Disease (DOHaD) hypothesis and highlight possible developmental programming mechanisms, including prenatal structural defects, metabolic (mitochondrial dysfunction, oxidative stress, protein modification), epigenetic and glucocorticoid signalling-related mechanisms suggesting molecular clues for the causes and consequences of programming of increased susceptibility of offspring to metabolic disease after birth. Identifying mechanisms involved in DOHaD can contribute to early interventions in pregnancy or 2 of 21 | GRILO et aL.

Cardiovascular disease (CVD) is the biggest killer worldwide, composing a major economic burden for health care systems. Obesity and diabetes are dual epidemics on the rise and major risk factors predisposing for CVD. Increased obesity‐ and diabetes‐related incidence is now observed among children, adolescents, and young adults. Gestational diabetes mellitus (GDM) is the most common metabolic pregnancy disorder, and its prevalence is rapidly increasing. During pregnancies complicated by GDM, the offspring are exposed to a compromised intrauterine environment characterized by hyperglycemic periods. Unfavorable in utero conditions at critical periods of fetal cardiac development can produce developmental adaptations that remodel the cardiovascular system in a way that can contribute to adult‐onset of heart disease due to the programming during fetal life. Epidemiological studies have reported increased cardiovascular complications among GDM‐descendants, highlighting the urgent need to investigate and understand the mechanisms modulated during fetal development of in utero GDM‐exposed offspring that predispose an individual to increased CVD during life. In this manuscript, we overview previous studies in this area and gather evidence linking GDM and CVD development in the offspring, providing new insights on novel mechanisms contributing to offspring CVD programming by GDM, from the role of maternal–fetal interactions to their impact on fetal cardiovascular development, how the perpetuation of cardiac programming is maintained in postnatal life, and advance the intergenerational implications contributing to increased CVD premature origin. Understanding the perpetuation of CVD can be the first step to manage and reverse this leading cause of morbidity and mortality. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Cardiovascular Diseases > Molecular and Cellular Physiology Metabolic Diseases > Genetics/Genomics/Epigenetics

Type 2 diabetes (T2D) has increased worldwide at an alarming rate. Metabolic syndrome (MetS) is a major risk factor for T2D development. One of the main reasons for the abrupt rise in MetS incidence, besides a sedentary lifestyle, is the westernized diet consumption, with high content of industrialized foods, rich in added dietary sugars (DS), mainly sucrose and fructose. It has been suggested that a higher intake of DS could impair metabolic function, inducing MetS, and predisposing to T2D. However, it remains poorly explored how excessive DS intake modulates mitochondrial function, a key player in metabolism. This review explores the relationship between increased consumption of DS and mitochondrial dysfunction associated with T2D development, pointing to a contribution of the diet-induced accumulation of advanced glycation end-products (AGEs), with brief insights on the impact of maternal high-sugar diet and AGEs consumption during gestation on offspring increased risk of developing T2D later in life, contributing to perpetuate T2D propagation.

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