Over the last few decades, the prevalence of obesity has risen to epidemic proportions worldwide. Consequently, the number of obesity in pregnancy has risen drastically. Gestational overweight and obesity are associated with impaired outcomes for mother and child. Furthermore, studies show that maternal obesity can lead to long-term consequences in the offspring, increasing the risk for obesity and cardiometabolic disease in later life. In addition to genetic mechanisms, mounting evidence demonstrates the induction of epigenetic alterations by maternal obesity, which can affect the offspring’s phenotype, thereby influencing the later risk of obesity and cardiometabolic disease. Clear evidence in this regard comes from various animal models of maternal obesity. Evidence derived from clinical studies remains limited. The current article gives an overview of pathophysiological changes associated with maternal obesity and their consequences on placental structure and function. Furthermore, a short excurse is given on epigenetic mechanisms and emerging data regarding a putative interaction between metabolism and epigenetics. Finally, a summary of important findings of animal and clinical studies investigating maternal obesity-related epigenetic effects is presented also addressing current limitations of clinical studies.

Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p < 0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p < 0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p = 0.001).

High-salt (HS) diets have recently been linked to oxidative stress in the brain, a fact that may be a precursor to behavioral changes, such as those involving anxiety-like behavior. However, to the best of our knowledge, no study has evaluated the amygdala redox status after consuming a HS diet in the pre- or postweaning periods. This study aimed to evaluate the amygdala redox status and anxiety-like behaviors in adulthood, after inclusion of HS diet in two periods: preconception, gestation, and lactation (preweaning); and only after weaning (postweaning). Initially, 18 females and 9 male Wistar rats received a standard (n = 9 females and 4 males) or a HS diet (n = 9 females and 5 males) for 120 days. After mating, females continued to receive the aforementioned diets during gestation and lactation. Weaning occurred at 21-day-old Wistar rats and the male offspring were subdivided: control-control (C-C)—offspring of standard diet fed dams who received a standard diet after weaning (n = 9–11), control-HS (C-HS)—offspring of standard diet fed dams who received a HS diet after weaning (n = 9–11), HS-C—offspring of HS diet fed dams who received a standard diet after weaning (n = 9–11), and HS-HS—offspring of HS diet fed dams who received a HS diet after weaning (n = 9–11). At adulthood, the male offspring performed the elevated plus maze and open field tests. At 152-day-old Wistar rats, the offspring were euthanized and the amygdala was removed for redox state analysis. The HS-HS group showed higher locomotion and rearing frequency in the open field test. These results indicate that this group developed hyperactivity. The C-HS group had a higher ratio of entries and time spent in the open arms of the elevated plus maze test in addition to a higher head-dipping frequency. These results suggest less anxiety-like behaviors. In the analysis of the redox state, less activity of antioxidant enzymes and higher levels of the thiobarbituric acid reactive substances (TBARS) in the amygdala were shown in the amygdala of animals that received a high-salt diet regardless of the period (pre- or postweaning). In conclusion, the high-salt diet promoted hyperactivity when administered in the pre- and postweaning periods. In animals that received only in the postweaning period, the addition of salt induced a reduction in anxiety-like behaviors. Also, regardless of the period, salt provided amygdala oxidative stress, which may be linked to the observed behaviors.

Das Konzept der fetalen Programmierung besagt, dass Umweltfaktoren, welche in der Embryonal- und Fetalzeit auf einen Organismus einwirken, weitreichende Folgen für den Gesundheitszustand im späteren Leben haben können. Wurde die fetale Programmierung anfangs vor allem mittels epidemiologischer Studien erforscht, gibt es mittlerweile auch viele experimentelle Arbeiten, die sich dem besseren Verständnis dieses biologischen Phänomens widmen. Es konnte gezeigt werden, dass eine Vielzahl an umweltbedingten Faktoren, wie zum Beispiel Ernährung, Stress, Schadstoffbelastung u. v. m., während der Gestation fetal programmierende Effekte entfalten kann. Neuere Studien deuten darauf hin, dass maternale Genvarianten ohne deren Vererbung den Phänotyp der Nachkommen im Sinne des Konzepts der fetalen Programmierung beeinflussen können. Darüber hinaus mehren sich die Hinweise, dass auch dem Vater eine relevante Rolle in der fetalen Programmierung zukommt. In den letzten Jahrzehnten konnten bezüglich der zugrunde liegenden Mechanismen der fetalen Programmierung viele neue Erkenntnisse gewonnen werden. Man geht inzwischen davon aus, dass epigenetische Mechanismen, also meiotisch bzw. mitotisch vererbbare Veränderungen der Genexpression, die nicht in der DNA selbst codiert sind, eine zentrale Rolle spielen. Viele Aspekte dieses noch recht jungen Forschungsgebiets sind jedoch bisher weiterhin wenig aufgeklärt, so zum Beispiel geschlechtsspezifische Unterschiede in der fetalen Programmierung. The fetal programming hypothesis states that environmental factors affecting an organism during embryonic and fetal development can alter its phenotype and susceptibility to disease in later life. First observations regarding fetal programming originated from epidemiological studies. There is now a considerable amount of experimental evidence that substantiated previous epidemiological findings and led to a better understanding of this biological phenomenon. It has been demonstrated that a variety of gestational environmental factors, such as nutrition, stress, pollution levels, etc., can result in fetal programming of phenotypic alterations in the offspring. Recent studies indicate that maternal genetic variants can influence the phenotype of the offspring without their inheritance through mechanisms of fetal programming. Furthermore, there is increasing scientific evidence that the father also plays a significant role in the developmental programming of his offspring. Many new insights into the underlying processes have been gained in recent decades and current evidence highlights that epigenetic mechanisms are vitally important in fetal programming. However, many aspects of this relatively novel scientific field of research remain poorly understood, such as sex-specific differences in fetal programming.