DOHaD, nutrition and basic research

DOHaD, NUTRITION AND BASIC RESEARCH C. Mandò, I. Cetin; Department of Biomedical and Clinical Sciences Luigi Sacco University of Milan, Milan, Italy The “DOHaD” (Developmental Origin of Health and Disease) theory describes how in utero exposure to environmental factors may have long-term effects on the structural and functional development of the fetus. Extensive retrospective studies, such as those on the Dutch famine of 1944, have reported correlations between maternal diet or nutritional status and the risk of pregnancy pathologies or to develop adverse conditions in the future adult. Indeed, macro- and micronutrients taken with the maternal diet can regulate the stability and expression of fetal/placental DNA and phenotype adaptations through epigenetic modifications, reversible mechanisms that occur without changes in the DNA sequence (DNA methylation, histone acetylation, microRNA) [1]. Recently, a large prospective longitudinal cohort study in humans (MANOE study) reported that maternal intake of methyl donors, especially during the periconceptional period, can affect the epigenoma of the offspring in genes related to obesity and diabetes. However, many observations on this issue are born from basic research studies performed on the placenta: placental epigenetic modifications are one of the main mechanisms through which nutritional and environmental factors affect fetal growth. Epigenetic regulation of placental phenotype and function has been extensively studied in the mouse. For example, “imprinted” placental genes (IGF2, H19) act as “nutritional sensors” by varying their methylation status based on environmental conditions. In our lab, we have recently reported lower functionality in the placenta of overweight/obese women with high gestational weight gain, with an important role in fetal sex [2]. Those placentas also exhibit alterations in mitochondrial content suggesting a bioenergetic placental imbalance resulting from an altered nutritional intake. Methylation of mitochondrial DNA may also be involved in these mechanisms [3]. Future research will allow to fully understand the underlying mechanisms of pregnancy pathologies in relation to maternal-fetal nutrition. REFERENCES [1] Vaiman D. Genes, epigenetics and miRNA regulation in the placenta. Placenta. 2017;52:127-33. [2] Mandò C, Calabrese S, Mazzocco MI, Novielli C, Anelli GM, Antonazzo P, Cetin I. Sex specific adaptations in placental biometry of overweight and obese women. Placenta. 2016;38:1-7. [3] Novielli C, Mandò C, Tabano S, Anelli GM, Fontana L, Antonazzo P, Miozzo M, Cetin I. Mitochondrial DNA content and methylation in fetal cord blood of pregnancies with placental insufficiency. Placenta. 2017;55:63-70.