RSS-Feed abonnieren
DOI: 10.1055/s-0028-1087109
Fetal Origins of Perinatal Morbidity and/or Adult Disease
Publikationsverlauf
Publikationsdatum:
29. September 2008 (online)
![](https://www.thieme-connect.de/media/srm/200805/lookinside/thumbnails/10.1055-s-0028-1087109-1.jpg)
ABSTRACT
The developmental origin of health and disease hypothesis holds that events occurring during the early development of an individual and specifically during intrauterine life have profound consequences on future health. Low birth weight, a marker of intrauterine stress, has been linked to predisposition to hypertension, cardiovascular diseases, diabetes, and stroke. The compelling animal evidence and significant human epidemiologic data to support this conclusion is reviewed. In addition, we propose that early embryo manipulation and culture that occur during use of assisted reproductive technologies may represent a stressful event that could be associated with future health problems. The effects of embryo culture on early development and gene expression and methylation status is reviewed and discussed.
KEYWORDS
Barker hypothesis - intrauterine stress - hypertension - cardiovascular disease - ART - low birth weight
REFERENCES
- 1 Barker D J. Mothers, Babies and Health in Later Life. Glasgow, Scotland; Churchill Livingstone 1998
- 2 Barker D J, Winter P D, Osmond C, Margetts B, Simmonds S J. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2 577-580
- 3 Godfrey K M, Barker D J. Fetal programming and adult health. Public Health Nutr. 2001; 4 611-624
- 4 Gluckman P D, Hanson M A. Developmental plasticity and human disease: research directions. J Intern Med. 2007; 261 461-471
- 5 O'Brien P MSWT, Barker D JP. Foetal Programming: Influences on Development and Disease in Later Life. London, United Kingdom; RCOG Press 1999
- 6 Morley R. Fetal origins of adult disease. Semin Fetal Neonatal Med. 2006; 11 73-78
- 7 Lawlor D A, Ronalds G, Clark H, Smith G D, Leon D A. Birth weight is inversely associated with incident coronary heart disease and stroke among individuals born in the 1950s: findings from the Aberdeen Children of the 1950s prospective cohort study. Circulation. 2005; 112 1414-1418
- 8 Leon D A, Lithell H O, Vagero D et al.. Reduced fetal growth rate and increased risk of death from ischaemic heart disease: cohort study of 15 000 Swedish men and women born 1915–29. BMJ. 1998; 317 241-245
- 9 Rich-Edwards J W, Kleinman K, Michels K B et al.. Longitudinal study of birth weight and adult body mass index in predicting risk of coronary heart disease and stroke in women. BMJ. 2005; 330 1115-1118
- 10 Barker D J, Eriksson J G, Forsen T, Osmond C. Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol. 2002; 31 1235-1239
- 11 Hypponen E, Leon D A, Kenward M G, Lithell H. Prenatal growth and risk of occlusive and haemorrhagic stroke in Swedish men and women born 1915–29: historical cohort study. BMJ. 2001; 323 1033-1034
- 12 Law C M, Shiell A W. Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature. J Hypertens. 1996; 14 935-941
- 13 Huxley R, Neil A, Collins R. Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure?. Lancet. 2002; 360 659-665
- 14 Cruickshank J K, Beith C, Koudsi A. Unravelling the fetal origins hypothesis. Lancet. 2002; 360 2073-2074; , author reply 2074–2075
- 15 Holemans K, Caluwaerts S, Van Assche F A. Unravelling the fetal origins hypothesis. Lancet. 2002; 360 2073; , author reply 2074–2075
- 16 Eriksson J G, Forsen T. Unravelling the fetal origins hypothesis. Lancet. 2002; 360 2072 , author reply 2074–2075
- 17 Hennessy E. Unravelling the fetal origins hypothesis. Lancet. 2002; 360 2072-2073 , author reply 2074–2075
- 18 Hemachandra A H, Klebanoff M A, Duggan A K, Hardy J B, Furth S L. The association between intrauterine growth restriction in the full-term infant and high blood pressure at age 7 years: results from the Collaborative Perinatal Project. Int J Epidemiol. 2006; 35 871-877
- 19 Menezes A M, Hallal P C, Horta B L et al.. Size at birth and blood pressure in early adolescence: a prospective birth cohort study. Am J Epidemiol. 2007; 165 611-616
- 20 Gamborg M, Byberg L, Rasmussen F et al.. Birth weight and systolic blood pressure in adolescence and adulthood: meta-regression analysis of sex- and age-specific results from 20 Nordic studies. Am J Epidemiol. 2007; 166 634-645
- 21 Shankaran S, Das A, Bauer C R et al.. Fetal origin of childhood disease: intrauterine growth restriction in term infants and risk for hypertension at 6 years of age. Arch Pediatr Adolesc Med. 2006; 160 977-981
- 22 Davies A A, Smith G D, May M T, Ben-Shlomo Y. Association between birth weight and blood pressure is robust, amplifies with age, and may be underestimated. Hypertension. 2006; 48 431-436
- 23 Stein A D, Zybert P A, van der Pal-de Bruin K, Lumey L H. Exposure to famine during gestation, size at birth, and blood pressure at age 59 y: evidence from the Dutch Famine. Eur J Epidemiol. 2006; 21 759-765
- 24 Mzayek F, Hassig S, Sherwin R et al.. The association of birth weight with developmental trends in blood pressure from childhood through mid-adulthood: the Bogalusa Heart study. Am J Epidemiol. 2007; 166 413-420
- 25 Hardy R, Sovio U, King V J et al.. Birthweight and blood pressure in five European birth cohort studies: an investigation of confounding factors. Eur J Public Health. 2006; 16 21-30
- 26 Gortner L. Intrauterine growth restriction and risk for arterial hypertension: a causal relationship?. J Perinat Med. 2007; 35 361-365
- 27 Halvorsen C P, Andolf E, Hu J, Pilo C, Winbladh B, Norman M. Discordant twin growth in utero and differences in blood pressure and endothelial function at 8 years of age. J Intern Med. 2006; 259 155-163
- 28 Vehaskari V M, Woods L L. Prenatal programming of hypertension: lessons from experimental models. J Am Soc Nephrol. 2005; 16 2545-2556
- 29 Martyn C N, Greenwald S E. A hypothesis about a mechanism for the programming of blood pressure and vascular disease in early life. Clin Exp Pharmacol Physiol. 2001; 28 948-951
- 30 Barker D JHC, Fall C H, Osmond C, Phipps K, Clark P. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologica. 1993; 36 62-67
- 31 Law C M, Gordon G S, Shiell A W, Barker D J, Hales C N. Thinness at birth and glucose tolerance in seven-year-old children. Diabet Med. 1995; 12 24-29
- 32 Rich-Edwards J W, Colditz G A, Stampfer M J et al.. Birthweight and the risk for type 2 diabetes mellitus in adult women. Ann Intern Med. 1999; 130 278-284
- 33 Hales C N, Barker D J, Clark P M et al.. Fetal and infant growth and impaired glucose tolerance at age 64. BMJ. 1991; 303 1019-1022
- 34 Lithell H O, McKeigue P M, Berglund L, Mohsen R, Lithell U B, Leon D A. Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50–60 years. BMJ. 1996; 312 406-410
- 35 Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med. 2000; 133 176-182
- 36 Newsome C A, Shiell A W, Fall C H, Phillips D I, Shier R, Law C M. Is birth weight related to later glucose and insulin metabolism? A systematic review. Diabet Med. 2003; 20 339-348
- 37 Mackenzie H S, Brenner B M. Fewer nephrons at birth: a missing link in the etiology of essential hypertension?. Am J Kidney Dis. 1995; 26 91-98
- 38 Brenner B M, Lawler E V, Mackenzie H S. The hyperfiltration theory: a paradigm shift in nephrology. Kidney Int. 1996; 49 1774-1777
- 39 Brenner B M, Chertow G M. Congenital oligonephropathy: an inborn cause of adult hypertension and progressive renal injury?. Curr Opin Nephrol Hypertens. 1993; 2 691-695
- 40 Brenner B M, Chertow G M. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis. 1994; 23 171-175
- 41 Mackenzie H S, Lawler E V, Brenner B M. Congenital oligonephropathy: the fetal flaw in essential hypertension?. Kidney Int Suppl. 1996; 55 S30-S34
- 42 Edwards C R, Benediktsson R, Lindsay R S, Seckl J R. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension?. Lancet. 1993; 341 355-357
- 43 Jaddoe V W, Witteman J C. Hypotheses on the fetal origins of adult diseases: contributions of epidemiological studies. Eur J Epidemiol. 2006; 21 91-102
- 44 Weaver I C, Cervoni N, Champagne F A et al.. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7 847-854
- 45 Francis D D, Caldji C, Champagne F, Plotsky P M, Meaney M J. The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry. 1999; 46 1153-1166
- 46 Francis D D, Diorio J, Plotsky P M, Meaney M J. Environmental enrichment reverses the effects of maternal separation on stress reactivity. J Neurosci. 2002; 22 7840-7843
- 47 Meaney M J, Bhatnagar S, Larocque S et al.. Individual differences in the hypothalamic-pituitary-adrenal stress response and the hypothalamic CRF system. Ann N Y Acad Sci. 1993; 697 70-85
- 48 Adamson G D, de Mouzon J, Lancaster P, Nygren K G, Sullivan E, Zegers-Hochschild F. World collaborative report on in vitro fertilization, 2000. Fertil Steril. 2006; 85 1586-1622
- 49 Kalra S K, Molinaro T A. The association of in vitro fertilization and perinatal morbidity. Semin Reprod Med. 2008; 26 423-435
- 50 Hansen M, Kurinczuk J J, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002; 346 725-730
- 51 Schieve L A, Meikle S F, Ferre C, Peterson H B, Jeng G, Wilcox L S. Low and very low birth weight in infants conceived with use of assisted reproductive technology. N Engl J Med. 2002; 346 731-737
- 52 Stromberg B, Dahlquist G, Ericson A, Finnstrom O, Koster M, Stjernqvist K. Neurological sequelae in children born after in-vitro fertilisation: a population-based study. Lancet. 2002; 359 461-465
- 53 Kovalevsky G, Rinaudo P, Coutifaris C. Do assisted reproductive technologies cause adverse fetal outcomes?. Fertil Steril. 2003; 79 1270-1272
- 54 Anthony S, Buitendijk S E, Dorrepaal C A, Lindner K, Braat D D, den Ouden A L. Congenital malformations in 4224 children conceived after IVF. Hum Reprod. 2002; 17 2089-2095
- 55 Wennerholm U B, Bergh C, Hagberg H, Sultan B, Wennergren M. Gestational age in pregnancies after in vitro fertilization: comparison between ultrasound measurement and actual age. Ultrasound Obstet Gynecol. 1998; 12 170-174
- 56 Bartolomei M S, Tilghman S M. Genomic imprinting in mammals. Annu Rev Genet. 1997; 31 493-525
- 57 Sutcliffe A G, Peters C J, Bowdin S et al.. Assisted reproductive therapies and imprinting disorders—a preliminary British survey. Hum Reprod. 2006; 21 1009-1011
- 58 Maher E R, Brueton L A, Bowdin S C et al.. Beckwith-Wiedemann syndrome and assisted reproduction technology (ART). J Med Genet. 2003; 40 62-64
- 59 DeBaun M R, Niemitz E L, Feinberg A P. Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003; 72 156-160
- 60 Chang A S, Moley K H, Wangler M, Feinberg A P, Debaun M R. Association between Beckwith-Wiedemann syndrome and assisted reproductive technology: a case series of 19 patients. Fertil Steril. 2005; 83 349-354
- 61 Gicquel C, Gaston V, Mandelbaum J, Siffroi J P, Flahault A, Le Bouc Y. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet. 2003; 72 1338-1341
- 62 Ludwig M, Katalinic A, Gross S, Sutcliffe A, Varon R, Horsthemke B. Increased prevalence of imprinting defects in patients with Angelman syndrome born to subfertile couples. J Med Genet. 2005; 42 289-291
- 63 Cox G F, Burger J, Lip V et al.. Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet. 2002; 71 162-164
- 64 Moll A IS, Cruysberg J, Schouten-van Meeteren A, Boers M, van Leeuwen F. Incidence of retinoblastoma in children born after in-vitro fertilization. Lancet. 2003; 361 309-310
- 65 Langley-Evans Sr S C, Welham S JM, Nwagwu M O, Gardner D S, Jackson A A. Intrauterine programming of hypertension: The role of renin-angiotensin system. Biochem Soc Trans. 1999; 27 88-93
- 66 Kwong W YWA, Roberts P, Willis A C, Fleming T P. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127 4195-4202
- 67 Walker S K, Hartwich K M, Robinson J S. Long-term effects on offspring of exposure of oocytes and embryos to chemical and physical agents. Hum Reprod Update. 2000; 6 564-577
- 68 Ogonuki N IK, Yamamoto Y, Noguchi Y et al.. Early death of mice cloned from somatic cells. Nat Genet. 2002; 30 253-254
- 69 Edwards J SF, McCracken M, Amstel S, Hopkins F, Welborn M, Davies C. Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer. Am J Reprod Immunol. 2003; 50 113-123
- 70 Kruip T A. In vitro produced and cloned embryos: effect on pregnancy, parturition and offspring. Theriogenology. 1997; 47 43-52
- 71 Willadsen S M. The developmental capacity of blastomeres. J Embryol Exp Morphol. 1981; 57 165-172
- 72 Ecker D J, Stein P, Xu Z et al.. Long-term effects of culture of preimplantation mouse embryos on behavior. Proc Natl Acad Sci U S A. 2004; 101 1595-1600
- 73 Fernandez-Gonzalez R, Moreira P, Bilbao A et al.. Long-term effect of in vitro culture of mouse embryos with serum on mRNA expression of imprinting genes, development, and behavior. Proc Natl Acad Sci U S A. 2004; 101 5880-5885
- 74 Dugan K J, Shalika S, Smith R D, Padilla S L. Comparison of synthetic serum substitute and fetal cord serum as media supplements for in vitro fertilization: a prospective, randomized study. Fertil Steril. 1997; 67 166-168
- 75 Ertzeid G, Storeng R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod. 2001; 16 221-225
- 76 Rinaudo P F, Giritharan G, Talbi S, Dobson A T, Schultz R M. Effects of oxygen tension on gene expression in preimplantation mouse embryos. Fertil Steril. 2006; 86(Suppl 4) 1252-1265
- 77 Lonergan P, Rizos D, Gutierrez-Adan A, Fair T, Boland M P. Effect of culture environment on embryo quality and gene expression—experience from animal studies. Reprod Biomed Online. 2003; 7 657-663
- 78 Gutierrez-Adan A, Rizos D, Fair T et al.. Effect of speed of development on mRNA expression pattern in early bovine embryos cultured in vivo or in vitro. Mol Reprod Dev. 2004; 68 441-448
- 79 Rinaudo P, Schultz R M. Effects of embryo culture on global pattern of gene expression in preimplantation mouse embryos. Reproduction. 2004; 128 301-311
- 80 Giritharan G, Talbi S, Dobson A T, Rosen M, Di Sebastiano F, Rinaudo P F. Embryo culture results in altered expression of specific imprinted genes in mouse blastocysts. Presented at: European Society of Human Reproduction and Embryology 2006 Prague, Czech Republic;
- 81 Giritharan G, Talbi S, Donjacour A, Di Sebastiano F, Dobson A T, Rinaudo P F. Effect of in vitro fertilization on gene expression and development of mouse preimplantation embryos. Reproduction. 2007; 134 63-72
- 82 Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987; 99 371-382
- 83 Kafri T, Ariel M, Brandeis M et al.. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 1992; 6 705-714
- 84 Doherty A S, Mann M R, Tremblay K D, Bartolomei M S, Schultz R M. Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod. 2000; 62 1526-1535
- 85 Li T, Vu T H, Ulaner G A et al.. IVF results in de novo DNA methylation and histone methylation at an Igf2–H19 imprinting epigenetic switch. Mol Hum Reprod. 2005; 11 631-640
- 86 Shi W, Haaf T. Aberrant methylation patterns at the two-cell stage as an indicator of early developmental failure. Mol Reprod Dev. 2002; 63 329-334
Paolo F RinaudoM.D. Ph.D.
Assistant Professor, Reproductive Endocrinology and Infertility, University of California San Francisco
2356 Sutter Street, 7th Floor, San Francisco, CA 94115
eMail: rinaudop@obgyn.ucsf.edu