Fetal Programlanma

Hamilelikte annenin beslenmesi fetal beslenme durumunu da belirler. Fetal beslenme yetersizliği varsa, fetüs yaşama şansını artırabilmek için vasküler, metabolik ve endokrin adaptasyonlar geliştirir. Bu adaptasyonlar erişkin dönemde de vücutta kalıcı yapı ve fonksiyon değişikliklerine yol açmakta, buna eklenen erişkin – yaşam risk faktörleri ile hipertansiyon, tip 2 diyabet, obezite ve hiperkolesterolemi riskini artırmaktadır. “Fetal programlanma” hipotezi hamilelikte ekzojen maternal malnütrisyonun fetüste yaşam boyu devam eden bir adaptasyona (insülin direncine) sebep olduğunu öne sürmektedir. Ayrıca bazı maternal genlerin, örneğin G protein β3 subünitesinin fetal malnütrisyona katkıda bulunabileceği ve bu adaptasyonu indükleyebileceği ileri sürülmüştür. Bu yazıda fetal programlanma ve bunu değiştirebilecek şartlar ile ilgili güncel bilgiler literatür ışığında derlendi.

Anahtar Kelimeler:

İntrauterin büyüme geriliği, fetal programlanma

FETAL PROGRAMMING

Maternal nutrition during pregnancy determines fetal nutrition. Impaired fetal nutrition causes an adaptation which improves the chance for survival of the fetus. These adaptations may be vascular, metabolic or endocrine. They permanently change the function and the structure of the body in adult life. In combination with adverse adult-life risk factors, these persisting fetal adaptations causing low-birth-weight increase the risk for adult diseases such as hypertension, insulin, resistance and hypercholesterolemia according to “ fetal programming” hypothesis. In addition, beside maternal malnutrition during pregnancy, maternal genes such as G protein β3 subunit allele may contribute to fetal malnutrition and therefore induce these adaptations of the fetus which causes cardiovascular disease in adult life. This review gives the current knowledge about fetal programming and its manipulation in the highlight of the literature

Keywords:

Intrauterine growth retardation, fetal programming,

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Ross MG, Beall MH. Adult sequelae of intrauterine growth restric- tion. Semin Perinatol. 2008;32:213-218.
Barker DJ, Osmond C: Low birth weight and hypertension. Br Med J 1988;297:134-135.
Barker DJ, Eriksson JG, Forsen T, Osmaond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 2002;31:1235-1239.
Bieswal F, Ahn MT, Reusens B, Holvoet P, Raes M, Rees WD, Remacle C. The importance of catch-up growth after early mal- nutrition for the programming of obesity in male rat. Obesity 2006;14:1330-1343.
Briana DD, Malamitsi-Puchner A. Intrauterine growth restriction and adult disease: the role of adipocytokines. Eur J Endocrinol. 2009;160:337-347.
Hauguel-de Mouzon S, Lepercq J, Catalano P. The known and unknown of leptin in pregnancy. Am J Obstet Gynecol 2006; 194:1537-1545.
Khorram O, Momeni M, Desai M, Ross MG. Nutrient restriction in utero induces remodeling of the vascular extracellular matrix in rat offspring. Reprod Sci 2007;14:73-80.
Shiell AW, Campbell DM, Hall MH, Barker DJ. Diet in late preg- nancy and glucose-insulin metabolism of the offspring 40 years later. Br J Obstet Gynaecol 2000;107:890–895.
Shiell AW, Campbell-Brown M, Haselden S, Robinson S, Godfrey KM, Barker DJ. High-meat, low-carbohydrate diet in pregnancy: relation to adult blood pressure in the offspring. Hypertension 2001;38:1282-1288.
Gressens P, Muaku SM, Besse L, Nsegbe E, Gallego J, Delpech B, Gaultier C, Evrard P, Ketelslegers JM, Maiter D. Maternal protein restriction early in rat pregnancy alters brain development in the progeny. Brain Res Dev Brain Res 1997;103:21–35.
Plagemann A, Harder T, Rake A, Melchior K, Rohde W, Dörner G. Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams. J Nutr 2000;130:2582–2589.
Chang GQ, Gaysinskaya V, Karatayev O, Leibowitz SF. Maternal high-fat diet and fetal programming: increased proliferation of hypothalamic peptide-producing neurons that increase risk for overeating and obesity. J Neurosci 2008;28:12107-12119.
Seckl JR, Meaney MJ. Glucocorticoid programming. Ann N Y Acad Sci 2004; 1032:63-84.
Jensen EC, Gallaher BW, Breier BH, Harding JE. The effect of a chronic maternal cortisol infusion on the lategestation fetal sheep. J Endocrinol 2002; 174:27-36.
Giraud GD, Louey S, Jonker S, Schultz J, Thornburg KL. Cortisol stimulates cell cycle activity in the cardiomyocyte of the sheep fe- tus. Endocrinology 2006; 147:3643-3649.
Antonow-Schlorke I, Schwab M, Li C, Nathanielsz PW. Glucocorticoid exposure at the dose used clinically alters cytoske- letal proteins and presynaptic terminals in the fetal baboon brain. Physiol. 2003;547(Pt 1):117-123.
Fonseca VM, Sichieri R, Moreira ME, Moura As. Early postnatal growth in preterm infants and cord blood leptin. J Perinatol 2006; 24:751-756.
King JC. Maternal obesity, metabolism, and pregnancy outcomes. Annu Rev Nutr 2006; 26:271-291.
Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005;115:911-919; quiz 920.
Cianfarani S, Martinez C, Maiorana A, Scire G, Spadoni GL, Boemi S. Adiponectin levels are reduced in children born small for gestational age and are inversely related to postnatal catch-up growth. J Clin Endocrinol Metab 2004;89:1346-1351.
Sancakli O, Darendeliler F, Bas F, Gokcay G, Disci R, Aki S, Eskiyurt N. Insulin, adiponectin, IGFBP-1 levels and body compo- sition in small for gestational age born non-obese children during prepubertal ages. Clin Endocrinol (Oxf) 2008;69:88–92.
Mendez-Ramirez F, Barbosa-Sabanero G, Romero-Gutierrez G, Malacara JM. Ghrelin in small for gestational age newborn babies:a cross-sectional study. Clin Endocrinol (Oxf) 2009;70 41–46.
Opsjon SL, Austgulen R, Waage A. Interleukin-1, interleukin-6 and tumor necrosis factor at delivery in preeclamptic disorders. Acta Obstet Gynecol Scand 1995;74:19-26.
Jefferies CA, Hofman PL, Keelan JA, Robinson EM, Cutfield WS. Insulin resistance is not due to persistently elevated serum tumor necrosis-alpha levels in small for gestational age, premature, or twin children. Pediatr Diabetes 2004;5: 20–25.
Ng PC, Lee CH, Lam CW, Chan IH, Wong E, Fok TF. Resistin in preterm and term newborns: relation to anthropometry, leptin, and insulin. Pediat Res 2005;58:725–730.
Li L, Yang G, Li Q, Tang Y, Yang M, Yang H, Li K. Changes and relations of circulating visfatin, apelin, and resistin levels in nor- mal, impaired glucose tolerance, and type 2 diabetic subjects. Exp Clin Endocrinol Diabetes 2006;114:544-8.
Jaquet D, Vidal H, Hankard R, Czernichow P, Levy-Marchal C. Impaired regulation of glucose transporter 4 gene expression in insulin resistance associated with in utero undernutrition. J Clin Endocrinol Metab 2001;86:3266-3271.
Klöting N, Berndt J, Kralisch S, Kovacs P, Fasshauer M, Schön MR, Stumvoll M, Blüher M. Vaspin gene expression in human adi- pose tissue: association with obesity and type 2 diabetes. Biochem Biophys Res Commun 2006;339:430-436.
Suleymanoglu S, Tascilar E, Pirgon O, Tapan S, Meral C, Abaci A. Vaspin and its correlation with insulin sensitivity indices in obese children. Diabetes Res Clin Pract 2009;84:325-328.
Desai M, Gayle D, Han G, Ross MG. Programmed hyperphagia due to reduced anorexigenic mechanisms in intrauterine growth- restricted offspring. Reprod Sci 2007;14:329-337.
Spiegelman BM, Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 1996;87:377-389.
Simmons RA, Templeton LJ, Gertz SJ. Intrauterine growth retarda- tion leads to the development of type 2 diabetes in the rat. Diabetes 2001;50:2279-2286.
Dallar Y, Dilli D, Bostanci I, Oğüş E, Doğankoç S, Tuğ E. Insulin sensitivity obtained from the oral glucose tolerance test and its re- lationship with birthweight. Ann Saudi Med 2007;27:13-17.
Pfab T, Slowinski T, Godes M, Halle H, Priem F, Hocher B. Low birth weight, a risk factor for cardiovascular diseases in later life, is already associated with elevated fetal glycosylated hemoglobin at birth. Circulation 2006;114:1687–1692.
Lane RH, MacLennan NK, Hsu JL, Janke SM, Pham TD. Increased hepatic peroxisome proliferator-activated receptor-gamma co- activator-1 gene expression in a rat model of intrauterine growth retardation and subsequent insulin resistance. Endocrinology 2002;143:2486-2490.
Aguiari P, Leo S, Zavan B, Vindigni V, Rimessi A, Bianchi K, Franzin C, Cortivo R, Rossato M, Vettor R, Abatangelo G, Pozzan T, Pinton P, Rizzuto R.. High glucose induces adipogenic diffe- rentiation of muscle-derived stem cells. Proc Natl Acad Sci USA 2008;105:1226–1231.
Du M, Yan X, Tong JF, Zhao J, Zhu MJ. Maternal obesity, inf- lammation, and fetal skeletal muscle development. Biol Reprod 2010;82:4-12.
Goodfellow J, Bellamy MF, Gorman ST, Brownlee M, Ramsey MW, Lewis MJ, Davies DP, Henderson AH. Endothelial function is impaired in fit young adults of low birth weight. Cardiovasc Res 1998;40:600-606.
Xu Y, Williams SJ, O’Brien D, Davidge ST. Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offs- pring. FASEB J 2006;20:1251-1253.
Langley-Evans SC. Developmental programming of health and di- sease. Proc Nutr Soc 2006; 65:97-105.
Petry CJ, Dorling MW, Wang CL, Pawlak DB, Ozanne SE. Catecholamine levels and receptor expression in low protein rat offspring. Diabet Med 2000;17:848-853.
Franco Mdo C, Dantas AP, Akamine EH, Kawamoto EM, Fortes ZB, Scavone C, Tostes RC, Carvalho MH, Nigro D. Enhanced oxi- dative stress as a potential mechanism underlying the programming of hypertension in utero. J Cardiovasc Pharmacol 2002;40:501- 509.
Khan OA, Torrens C, Noakes DE, Poston L, Hanson MA, Green LR, Ohri SK. Effects of pre-natal and early post-natal undernutri- tion on adult internal thoracic artery function. Eur J Cardiothorac Surg 2005;28:811-815.
Ojeda NB, Grigore D, Alexander BT. Role of fetal programming in the development of hypertension. Future Cardiol 2008;4:163-174.
Jennings BJ, Ozanne SE, Dorling MW, Hales CN. Early growth determines longevity in male rats and may be related to telomere shortening in the kidney. FEBS Lett 1999;448:4–8.
Thamotharan M, Garg M, Oak S, Rogers LM, Pan G, Sangiorgi F, Lee PW, Devaskar SU, Transgenerational inheritance of the insu- lin resistant phenotype in embryo-transferred intra-uterine growth restricted adult female rat offspring. Am J Physiol Endocrinol Metab 2007;292:E1270-E1279.
Holness MJ, Sugden MC. Epigenetic regulation of metabolism in children born small for gestational age. Curr Opin Clin Nutr Metab Care 2006;9:482-488.
Burdge GC, Lillycrop KA, Jackson AA. Nutrition in early life, and risk of cancer and metabolic disease: alternative endings in an epi- genetic tale? Br J Nutr. 2009;101:619–630.
Ekbom. The developmental environment and the early origins of cancer. In: Gluckman, PD.; Hanson, MA., editors. Developmental Origins of Disease. Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, San Paulo: Cambridge University Press; 2006. p. 415-425.
Levin BE. Metabolic imprinting: critical impact of the perinatal environment on the regulation of energy homeostasis. Phil Trans R Soc Lond B Biol Sci 2006; 361:1107-1121.
Roseboom TJ, van der Meulen JH, Ravelli AC, Osmond C, Barker DJ, Bleker OP. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Mol Cell Endocrinol 2001;185:93–98.
Stanner SA, Bulmer K, Andrès C, Lantseva OE, Borodina V, Poteen VV, Yudkin JS. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study. Br Med J 1997;315:1342- 1348.
Torrens C, Brawley L, Anthony FW Dance CS, Dunn R, Jackson AA, Poston L, Hanson MA. Folate supplementation during preg- nancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension 2006;47:982-987.
Brawley L, Torrens C, Anthony FW, Itoh S, Wheeler T, Jackson AA, Clough GF, Poston L, Hanson MA. Glycine rectifies vascu- lar dysfunction induced by dietary protein imbalance during preg- nancy. J Physiol 2004; 554:497-504.
Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC. Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glyci- ne. Clin Sci (London) 2002;103;633–639.
Anderson EA and Mark AL. The vasodilator action of insu- lin. Implications for the insulin hypothesis of hypertension. Hypertension 1993;21:136-141.
Vickers MH, Gluckman PD, Coveny AH, Hofman PL, Cutfield WS, Gertler A, Breier BH, Harris M. Neonatal leptin treatment reverses developmental programming. Neonatal leptin treatment reverses developmental programming. Endocrinology 2005;146:4211- 4216.
Akcurin S, Velipasaoglu S, Akcurin G, Guntekin M. Leptin profi- le in neonatal gonadotropin surge and relationship between leptin and body mass index in early infancy. J Pediatr Endocrinol Metab 2005;18:189-195.