Metabolic imprinting

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Metabolic imprinting refers to the long-term physiological and metabolic effects that an offspring's prenatal and postnatal environments have on them. [1] Perinatal nutrition has been identified as a significant factor in determining an offspring's likelihood of it being predisposed to developing cardiovascular disease, obesity, and type 2 diabetes amongst other conditions. [2]

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During pregnancy, maternal glucose can cross the blood-placental barrier [3] meaning maternal hyperglycaemia is associated with foetal hyperglycaemia. [4] Despite maternal glucose being able to cross the blood-placental barrier, maternal insulin is not able and the foetus has to make its own. [5] [6] As a result, if a mother is hyperglycaemic the foetus is likely to be hyperinsulinaemic which leads to it having increased levels of growth and adiposity. [4]

Maternal undernutrition

Affects of maternal nutrition.gif

Maternal undernutrition has been linked with low birth weight and also a number of diseases, including Cardiovascular disease, stroke, hypertension and diabetes. [7] When a foetus is in the womb and is not receiving sufficient nutrition, it can adapt to prioritize organ growth and increased metabolic efficiency to prepare itself for life in an energy deficient environment. Postnatally, when given the correct nutrition, babies exhibit ‘catch up growth’, potentially leading to obesity and other related complications. Studies based around restricting animals food intake throughout gestation have discovered that a reduction of just 30% of normal intake can cause low birth weight and increase sensitivity to high-fat-diet induced obesity. [8]

In animal models, intrauterine undernutrition has been shown to be associated with hypertension later in life. This is because the formation of the kidneys is inhibited, which decreases filtration and flow rate through the nephrons, leading to increased blood pressure. [9]

More extreme prenatal conditions such as famine have been shown to have effects on the neurodevelopment of a foetus. [7] After the Dutch Famine of the winter of 1944–1945, it was found that the risk of schizophrenia was significantly higher in those conceived at the height of the famine, as was the prevalence of schizoid personality. [10]

Maternal over-nutrition

Maternal overnutrition can have detrimental effects on the health of the offspring later in life. This area is less well studied and understood but some progress has been made in identifying specific genes that are affected. [7] Studies have investigated hypermethylation of DNA and found it to be higher in obese mothers to those of a healthy BMI. [11] More specific studies have investigated Leptin (LEP) as a possible gene which is altered via metabolic imprinting in response to overnutrition in utero, and found hypermethylation of LEP in the placenta of those born to overly nourished mothers. [12] This hypermethylation has been found to cause changes in the levels of circulating Leptin, as well as to leptin sensitivity and the development of neural circuits involved in the control of homeostasis which causes the higher risk of metabolic disease.

Upon investigation it was found that a mother who was obese before conception was likely to have a higher level of placental LEP than the placenta of a mother of a healthy weight. [12] One strategy for overcoming obesity is the use of gastric bypass and other such surgeries, while this does not entirely alleviate the risk of altered metabolic imprinting it has been found that siblings born post maternal surgery are less likely to have as high body fat percentages than over nutrition as siblings born before the surgery. [13]

Paternal overnutrition can also have a detrimental effect and new-borns have shown changes in methylation of DNA generally, with substantial hypomethylation at the gene Insulin-like Growth factor 2 (IGF2). However, this topic is much less studied than maternal nutrition. [13]

Maternal/gestational diabetes

An increase in certain hormones such as oestrogen, progesterone, human placental lactogen, human placental growth hormone and cortisol during the second and third trimester of pregnancy cause an increase in insulin resistance. This increase in insulin resistance and following increase in insulin secretion ensures that the foetus develops a normal glucose tolerance. [14] Gestational Diabetes Mellitus (GDM) arises when beta cells do not secrete enough insulin to adopt to the insulin resistance triggered by pregnancy, which leads to mild hyperglycaemia. [15]

Although the mechanisms are still largely unknown, foetus exposure to GDM and maternal diabetes has been shown to lead to lifelong metabolic complications because of metabolic imprinting. The risk of Type II diabetes developing in offspring is significantly higher in offspring where the mother was diagnosed with Type II diabetes before pregnancy rather than after. In addition, the age at which offspring are diagnosed with Type 2 diabetes is significantly younger in offspring exposed to maternal diabetes/GDM than those who are not. It is suggested that this is a result of DNA methylation during foetal development. [14]

Related Research Articles

<span class="mw-page-title-main">Intrauterine growth restriction</span> Medical condition

Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.

A maternal effect is a situation where the phenotype of an organism is determined not only by the environment it experiences and its genotype, but also by the environment and genotype of its mother. In genetics, maternal effects occur when an organism shows the phenotype expected from the genotype of the mother, irrespective of its own genotype, often due to the mother supplying messenger RNA or proteins to the egg. Maternal effects can also be caused by the maternal environment independent of genotype, sometimes controlling the size, sex, or behaviour of the offspring. These adaptive maternal effects lead to phenotypes of offspring that increase their fitness. Further, it introduces the concept of phenotypic plasticity, an important evolutionary concept. It has been proposed that maternal effects are important for the evolution of adaptive responses to environmental heterogeneity.

<span class="mw-page-title-main">Gestational diabetes</span> Medical condition

Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of needing a Caesarean section. Babies born to mothers with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. If untreated, diabetes can also result in stillbirth. Long term, children are at higher risk of being overweight and of developing type 2 diabetes.

Thrifty phenotype refers to the correlation between low birth weight of neonates and the increased risk of developing metabolic syndromes later in life, including type 2 diabetes and cardiovascular diseases. Although early life undernutrition is thought to be the key driving factor to the hypothesis, other environmental factors have been explored for their role in susceptibility, such as physical inactivity. Genes may also play a role in susceptibility of these diseases, as they may make individuals predisposed to factors that lead to increased disease risk.

<span class="mw-page-title-main">Birth weight</span> Weight of a human baby at birth

Birth weight is the body weight of a baby at its birth. The average birth weight in babies of European and African descent is 3.5 kilograms (7.7 lb), with the normative range between 2.5 and 4.0 kilograms. On average, babies of Asian descent weigh about 3.25 kilograms (7.2 lb). The prevalence of low birth weight has changed over time. Trends show a slight decrease from 7.9% (1970) to 6.8% (1980), then a slight increase to 8.3% (2006), to the current levels of 8.2% (2016). The prevalence of low birth weights has trended slightly upward from 2012 to the present.

<span class="mw-page-title-main">Diabetes and pregnancy</span> Effects of pre-existing diabetes upon pregnancy

For pregnant women with diabetes, some particular challenges exist for both mother and child. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.

<span class="mw-page-title-main">Intrauterine hypoxia</span> Medical condition when the fetus is deprived of sufficient oxygen

Intrauterine hypoxia occurs when the fetus is deprived of an adequate supply of oxygen. It may be due to a variety of reasons such as prolapse or occlusion of the umbilical cord, placental infarction, maternal diabetes and maternal smoking. Intrauterine growth restriction may cause or be the result of hypoxia. Intrauterine hypoxia can cause cellular damage that occurs within the central nervous system. This results in an increased mortality rate, including an increased risk of sudden infant death syndrome (SIDS). Oxygen deprivation in the fetus and neonate have been implicated as either a primary or as a contributing risk factor in numerous neurological and neuropsychiatric disorders such as epilepsy, attention deficit hyperactivity disorder, eating disorders and cerebral palsy.

<span class="mw-page-title-main">Human placental lactogen</span> Polypeptide placental hormone in humans

Human placental lactogen (hPL), also called human chorionic somatomammotropin (hCS) or human chorionic somatotropin, is a polypeptide placental hormone, the human form of placental lactogen. Its structure and function are similar to those of human growth hormone. It modifies the metabolic state of the mother during pregnancy to facilitate energy supply to the fetus. hPL has anti-insulin properties. hPL is a hormone secreted by the syncytiotrophoblast during pregnancy. Like human growth hormone, hPL is encoded by genes on chromosome 17q22-24. It was identified in 1963.

Maternal obesity refers to obesity of a woman during pregnancy. Parental obesity refers to obesity of either parent during pregnancy.

<span class="mw-page-title-main">Placental disease</span> Medical condition

A placental disease is any disease, disorder, or pathology of the placenta.

<span class="mw-page-title-main">Prenatal nutrition</span>

Prenatal nutrition addresses nutrient recommendations before and during pregnancy. Nutrition and weight management before and during pregnancy has a profound effect on the development of infants. This is a rather critical time for healthy development since infants rely heavily on maternal stores and nutrient for optimal growth and health outcome later in life.

Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.

Developmental Origins of Health and Disease is an approach to medical research factors that can lead to the development of human diseases during early life development. These factors include the role of prenatal and perinatal exposure to environmental factors, such as undernutrition, stress, environmental chemical, etc. This approach includes an emphasis on epigenetic causes of adult chronic non-communicable diseases. As well as physical human disease, the psychopathology of the foetus can also be predicted by epigenetic factors.

Obstetric medicine, similar to maternal medicine, is a sub-specialty of general internal medicine and obstetrics that specializes in process of prevention, diagnosing, and treating medical disorders in with pregnant women. It is closely related to the specialty of maternal-fetal medicine, although obstetric medicine does not directly care for the fetus. The practice of obstetric medicine, or previously known as "obstetric intervention," primarily consisted of the extraction of the baby during instances of duress, such as obstructed labor or if the baby was positioned in breech.

The fetal origins hypothesis proposes that the period of gestation has significant impacts on the developmental health and wellbeing outcomes for an individual ranging from infancy to adulthood. The effects of fetal origin are marked by three characteristics: latency, wherein effects may not be apparent until much later in life; persistency, whereby conditions resulting from a fetal effect continue to exist for a given individual; and genetic programming, which describes the 'switching on' of a specific gene due to prenatal environment. Research in the areas of economics, epidemiology, and epigenetics offer support for the hypothesis.

Maternal fetal stress transfer is a physiological phenomenon in which psychosocial stress experienced by a mother during her pregnancy can be transferred to the fetus. Psychosocial stress describes the brain's physiological response to perceived social threat. Because of a link in blood supply between a mother and fetus, it has been found that stress can leave lasting effects on a developing fetus, even before a child is born. According to recent studies, these effects are mainly the result of two particular stress biomarkers circulating in the maternal blood supply: cortisol and catecholamines.

Fetal programming, also known as prenatal programming, is the theory that environmental cues experienced during fetal development play a seminal role in determining health trajectories across the lifespan.

The first 1000 days describes the period from conception to 24 months of age in child development. This is considered a "critical period" in which sufficient nutrition and environmental factors have life-long effects on a child's overall health. While adequate nutrition can be exceptionally beneficial during this critical period, inadequate nutrition may also be detrimental to the child. This is because children establish many of their lifetime epigenetic characteristics in their first 1000 days. Medical and public health interventions early on in child development during the first 1000 days may have higher rates of success compared to those achieved outside of this period.

<span class="mw-page-title-main">Diabetic embryopathy</span> Medical condition

Diabetic embryopathy refers to congenital maldevelopments that are linked to maternal diabetes. Prenatal exposure to hyperglycemia can result in spontaneous abortions, perinatal mortality, and malformations. Type 1 and Type 2 diabetic pregnancies both increase the risk of diabetes induced teratogenicity. The rate of congenital malformations is similar in Type 1 and 2 mothers because of increased adiposity and the age of women with type 2 diabetes. Genetic predisposition and different environmental factors both play a significant role in the development of diabetic embryopathy. Metabolic dysfunction in pregnant mothers also increases the risk of fetal malformations.

Nutritional epigenetics is a science that studies the effects of nutrition on gene expression and chromatin accessibility. It is a subcategory of nutritional genomics that focuses on the effects of bioactive food components on epigenetic events.

References

  1. ↑ Sullivan EL, Grove KL (2010). "Metabolic imprinting in obesity". Forum of Nutrition. 63: 186–194. doi:10.1159/000264406. ISBN   978-3-8055-9300-7. PMC   3255478 . PMID   19955786.
  2. ↑ Lau C, Rogers JM (December 2004). "Embryonic and fetal programming of physiological disorders in adulthood". Birth Defects Research Part C: Embryo Today: Reviews. 72 (4): 300–12. doi:10.1002/bdrc.20029. PMID   15662709.
  3. ↑ Donnelly L, Campling G (March 2014). "Functions of the placenta". Anaesthesia & Intensive Care Medicine. 15 (3): 136–9. doi:10.1016/j.mpaic.2014.01.004.
  4. 1 2 Contreras M, Sacks DA, Bowling FG, Cowley DM, Liley H, McIntyre HD, Tudehope DI, et al. (HAPO Study Cooperative Research Group.) (July 2002). "The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study". International Journal of Gynaecology and Obstetrics. 78 (1): 69–77. doi:10.1016/s0020-7292(02)00092-9. PMID   12113977. S2CID   68389809.
  5. ↑ Oken E, Gillman MW (April 2003). "Fetal origins of obesity". Obesity Research. 11 (4): 496–506. doi: 10.1038/oby.2003.69 . PMID   12690076.
  6. ↑ Freinkel N (December 1980). "Banting Lecture 1980. Of pregnancy and progeny". Diabetes. 29 (12): 1023–35. doi:10.2337/diab.29.12.1023. PMID   7002669. S2CID   27125111.
  7. 1 2 3 Levin BE (July 2006). "Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 361 (1471): 1107–21. doi:10.1098/rstb.2006.1851. PMC   1642705 . PMID   16815795.
  8. ↑ Levin BE (July 2000). "The obesity epidemic: metabolic imprinting on genetically susceptible neural circuits". Obesity Research. 8 (4): 342–7. doi: 10.1038/oby.2000.41 . PMID   10933311.
  9. ↑ Hanley B, Dijane J, Fewtrell M, Grynberg A, Hummel S, Junien C, et al. (July 2010). "Metabolic imprinting, programming and epigenetics - a review of present priorities and future opportunities". The British Journal of Nutrition. 104 (S1): S1-25. doi:10.1017/s0007114510003338. PMID   20929595. S2CID   10008335.
  10. ↑ Susser E, Hoek HW, Brown A (February 1998). "Neurodevelopmental disorders after prenatal famine: The story of the Dutch Famine Study". American Journal of Epidemiology. 147 (3): 213–6. doi: 10.1093/oxfordjournals.aje.a009439 . PMID   9482494.; "Erratum: Neurodevelopmental disorders after prenatal famine: The story of the Dutch Famine Study". American Journal of Epidemiology. 148 (11): 1135. doi:10.1093/oxfordjournals.aje.a009597.
  11. ↑ Duan JE, Zhang M, Flock K, Seesi SA, Mandoiu I, Jones A, et al. (2018-08-03). "Effects of maternal nutrition on the expression of genomic imprinted genes in ovine fetuses". Epigenetics. 13 (8): 793–807. doi:10.1080/15592294.2018.1503489. PMC   6224220 . PMID   30051747.
  12. 1 2 Moreno-Fernandez J, Ochoa JJ, Lopez-Frias M, Diaz-Castro J (December 2020). "Impact of Early Nutrition, Physical Activity and Sleep on the Fetal Programming of Disease in the Pregnancy: A Narrative Review". Nutrients. 12 (12): 3900. doi: 10.3390/nu12123900 . PMC   7766505 . PMID   33419354.
  13. 1 2 Dunford AR, Sangster JM (December 2017). "Maternal and paternal periconceptional nutrition as an indicator of offspring metabolic syndrome risk in later life through epigenetic imprinting: A systematic review". Diabetes & Metabolic Syndrome. SI: Online Supplement - 2. 11 (Suppl 2): S655–S662. doi:10.1016/j.dsx.2017.04.021. PMID   28533070.
  14. 1 2 Burlina S, Dalfrà MG, Lapolla A (February 2019). "Short- and long-term consequences for offspring exposed to maternal diabetes: a review". The Journal of Maternal-Fetal & Neonatal Medicine. 32 (4): 687–694. doi:10.1080/14767058.2017.1387893. PMID   28969466. S2CID   23067468.
  15. ↑ McIntyre HD, Catalano P, Zhang C, Desoye G, Mathiesen ER, Damm P (July 2019). "Gestational diabetes mellitus". Nature Reviews. Disease Primers. 5 (1): 47. doi:10.1038/s41572-019-0098-8. PMID   31296866. S2CID   195893390.
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