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DOHaD, nutrition and basic research
Full text linkDOHaD, 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
Is it time for clinical use of LMWH in women with adverse pregnancy outcome or do we need large-scale prospective studies?
No full textPlacental transport of amino acids in normal and growth-restricted pregnancies
No full textIn human pregnancies placental amino acid transport has been studied at the time of delivery and also by in utero fetal blood sampling (FBS). A significant reduction in amino acid fetal-maternal gradients and in umbilical veno-arterial differences has been demonstrated in intrauterine growth-restricted (IUGR) pregnancies. Fetal-maternal transfer rates have been further investigated in vivo by stable isotope methodologies. Following a maternal bolus infusion of [1-13C]-glycine and [1-13C]-leucine performed at fetal blood sampling, the transfer rate of the non-essential amino acid glycine is significantly lower than that for the essential amino acid leucine, suggesting that glycine can be newly synthesized in the feto-placental unit. Moreover, in growth-restricted pregnancies the fetal/maternal ratio of [1-13C]-leucine is significantly lower, and proportional to the degree of severity. In vitro studies have described a variety of transport systems for amino acids within the microvillous membrane (MVM) and the basal membrane (BM) of the placenta and significant differences have been reported in growth-restricted pregnancies for system A, system L, and taurine transporters. These changes are significantly associated to both biophysical and biochemical parameters of severity. Moreover, significant relationships can be found in arginine transport system and uterine oxygenation, suggesting a role in nitric oxide (NO) synthesis
Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo
No full textFetal growth and development are dependent upon the adequate provision of oxygen and substrates from the maternal circulation. The need for amino acids is related to protein synthesis, interconversion to other substrates, and oxidation. Amino acids cross the placenta by active transport systems, and their concentrations in the fetus are higher than in the mother. In addition, most amino acids are extensively metabolized within the placenta, and, for some nonessential amino acids, placental synthesis has been demonstrated in chronically catheterized fetal lambs. Interorgan cycling between the fetal liver and placenta has been hypothesized for nonessential amino acids like glycine and serine. Amino acids are oxidized within the fetal tissues, particularly in liver and muscle, with differences between amino acids and in relation to metabolic state. In human pregnancies, maternal-fetal transfer rates have been investigated in vivo by stable isotope methodologies performed at fetal blood sampling. The transfer rate of nonessential amino acids like glycine is significantly lower than for essential amino acids like leucine, confirming glycine synthesis in the fetoplacental unit also in human pregnancies. Moreover, when a steady state model is applied, the fetal-maternal ratio for [1-(13)C]leucine is significantly reduced in pregnancies associated with intrauterine growth restriction, reflecting a decrease in leucine placental transfer and/or an increase in protein catabolism in the fetoplacental unit. This reduction is proportional to the degree of severity of intrauterine growth restriction but is significant also in those intrauterine growth-restricted fetuses with normal oxygenation and acid-base status
Procedimento per la predizione del rischio associato a patologie placentari attraverso quantificazione del DNA mitocondriale
No full textProcedimento per la predizione del rischio associato a patologie placentari attraverso quantificazione del DNA mitocondrial
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