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