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Embryos, DOHaD and David Barker

Published online by Cambridge University Press:  08 May 2015

T. P. Fleming*
Affiliation:
Centre for Biological Sciences, University of Southampton, Southampton, UK
M. A. Velazquez
Affiliation:
Centre for Biological Sciences, University of Southampton, Southampton, UK
J. J. Eckert
Affiliation:
Faculty of Medicine, University of Southampton, Southampton, UK
*
*Address for correspondence: T. P. Fleming, Centre for Biological Sciences, University of Southampton, Southampton SO16 6YD, UK. (Email tpf@soton.ac.uk)

Abstract

The early embryo and periconceptional period is a window during which environmental factors may cause permanent change in the pattern and characteristics of development leading to risk of adult onset disease. This has now been demonstrated across small and large animal models and also in the human. Most evidence of periconceptional ‘programming’ has emerged from maternal nutritional models but also other in vivo and in vitro conditions including assisted reproductive treatments, show consistent outcomes. This short review first reports on the range of environmental in vivo and in vitro periconceptional models and resulting long-term outcomes. Second, it uses the rodent maternal low protein diet model restricted to the preimplantation period and considers the stepwise maternal-embryonic dialogue that comprises the induction of programming. This dialogue leads to cellular and epigenetic responses by the embryo, mainly identified in the extra-embryonic cell lineages, and underpins an apparently permanent change in the growth trajectory during pregnancy and associates with increased cardiometabolic and behavioural disease in adulthood. We recognize the important advice of David Barker some years ago to investigate the sensitivity of the early embryo to developmental programming, an insight for which we are grateful.

Type
Review
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

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References

1. Roseboom, TJ, Painter, RC, van Abeelen, AF, Veenendaal, MV, de Rooij, SR. Hungry in the womb: what are the consequences? Lessons from the Dutch famine. Maturitas. 2011; 70, 141145.Google Scholar
2. Hart, R, Norman, RJ. The longer-term health outcomes for children born as a result of IVF treatment: Part I--General health outcomes. Hum Reprod Update. 2013; 19, 232243.Google Scholar
3. Fleming, TP, Watkins, AJ, Sun, C, et al. Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health. Reprod Fertil Dev. 2015; 27, 684692.Google Scholar
4. Fleming, TP, Velazquez, MA, Eckert, JJ, Lucas, ES, Watkins, AJ. Nutrition of females during the peri-conceptional period and effects on foetal programming and health of offspring. Anim Reprod Sci. 2012; 130, 193197.CrossRefGoogle ScholarPubMed
5. El Hajj, N, Haaf, T. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril. 2013; 99, 632641.CrossRefGoogle ScholarPubMed
6. Zhang, S, Rattanatray, L, Morrison, JL, et al. Maternal obesity and the early origins of childhood obesity: weighing up the benefits and costs of maternal weight loss in the periconceptional period for the offspring. Exp Diabetes Res. 2011; 2011, 585749.CrossRefGoogle ScholarPubMed
7. Jungheim, ES, Moley, KH. Current knowledge of obesity’s effects in the pre- and periconceptional periods and avenues for future research. Am J Obstet Gynecol. 2010; 203, 525530.Google Scholar
8. McMillen, IC, MacLaughlin, SM, Muhlhausler, BS, et al. Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition. Basic Clin Pharmacol Toxicol. 2008; 102, 8289.CrossRefGoogle ScholarPubMed
9. Watkins, AJ, Ursell, E, Panton, R, et al. Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease. Biol Reprod. 2008; 78, 299306.CrossRefGoogle ScholarPubMed
10. Watkins, AJ, Lucas, ES, Torrens, C, et al. Maternal low-protein diet during mouse pre-implantation development induces vascular dysfunction and altered renin-angiotensin-system homeostasis in the offspring. Br J Nutr. 2010; 103, 17621770.CrossRefGoogle ScholarPubMed
11. Watkins, AJ, Lucas, ES, Wilkins, A, Cagampang, FR, Fleming, TP. Maternal periconceptional and gestational low protein diet affects mouse offspring growth, cardiovascular and adipose phenotype at 1 year of age. PLoS One. 2011; 6, e28745.CrossRefGoogle ScholarPubMed
12. Kwong, WY, Wild, AE, Roberts, P, Willis, AC, Fleming, TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127, 41954202.Google Scholar
13. Watkins, AJ, Wilkins, A, Cunningham, C, et al. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J Physiol. 2008; 586, 22312244.CrossRefGoogle ScholarPubMed
14. Torrens, C, Snelling, TH, Chau, R, et al. Effects of pre- and periconceptional undernutrition on arterial function in adult female sheep are vascular bed dependent. Exp Physiol. 2009; 94, 10241033.Google Scholar
15. Todd, SE, Oliver, MH, Jaquiery, AL, Bloomfield, FH, Harding, JE. Periconceptional undernutrition of ewes impairs glucose tolerance in their adult offspring. Pediatr Res. 2009; 65(4), 409413.Google Scholar
16. Hernandez, CE, Matthews, LR, Oliver, MH, Bloomfield, FH, Harding, JE. Effects of sex, litter size and periconceptional ewe nutrition on offspring behavioural and physiological response to isolation. Physiol Behav. 2010; 101, 588594.CrossRefGoogle ScholarPubMed
17. Sinclair, KD, Allegrucci, C, Singh, R, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proc Natl Acad Sci U S A. 2007; 104, 1935119356.Google Scholar
18. Li, Y, Jaddoe, VW, Qi, L, et al. Exposure to the Chinese famine in early life and the risk of hypertension in adulthood. J Hyperten. 2011; 29(6), 10851092.CrossRefGoogle Scholar
19. Xu, MQ, Sun, WS, Liu, BX, et al. Prenatal malnutrition and adult schizophrenia: further evidence from the 1959–1961 Chinese famine. Schizophr Bull. 2009; 35, 568576.CrossRefGoogle ScholarPubMed
20. Lane, M, Zander-Fox, DL, Robker, RL, McPherson, NO. Peri-conception parental obesity, reproductive health, and transgenerational impacts. Trends Endocrinol Metab. 2015; 26, 8490.CrossRefGoogle ScholarPubMed
21. Tenenbaum-Gavish, K, Hod, M. Impact of maternal obesity on fetal health. Fetal Diag Ther. 2013; 34, 17.Google Scholar
22. O’Reilly, JR, Reynolds, RM. The risk of maternal obesity to the long-term health of the offspring. Clin Endocrinol. 2013; 78, 916.CrossRefGoogle Scholar
23. Ruager-Martin, R, Hyde, MJ, Modi, N. Maternal obesity and infant outcomes. Early Hum Dev. 2010; 86, 715722.Google Scholar
24. Alfaradhi, MZ, Ozanne, SE. Developmental programming in response to maternal overnutrition. Front Genet. 2011; 2, 27.Google Scholar
25. Picone, O, Laigre, P, Fortun-Lamothe, L, et al. Hyperlipidic hypercholesterolemic diet in prepubertal rabbits affects gene expression in the embryo, restricts fetal growth and increases offspring susceptibility to obesity. Theriogenology. 2011; 75, 287299.CrossRefGoogle ScholarPubMed
26. Dunning, KR, Russell, DL, Robker, RL. Lipids and oocyte developmental competence: the role of fatty acids and beta-oxidation. Reproduction. 2014; 148, R1527.Google Scholar
27. Nicholas, LM, Morrison, JL, Rattanatray, L, et al. Differential effects of exposure to maternal obesity or maternal weight loss during the periconceptional period in the sheep on insulin signalling molecules in skeletal muscle of the offspring at 4 months of age. PLoS One. 2013; 8, e84594.Google Scholar
28. Sasson, IE, Vitins, AP, Mainigi, MA, Moley, KH, Simmons, RA. Pre-gestational vs gestational exposure to maternal obesity differentially programs the offspring in mice. Diabetologia. 2015; 58, 615624.CrossRefGoogle ScholarPubMed
29. Luzzo, KM, Wang, Q, Purcell, SH, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One. 2012; 7, e49217.CrossRefGoogle ScholarPubMed
30. Turner, N, Robker, RL. Developmental programming of obesity and insulin resistance: does mitochondrial dysfunction in oocytes play a role? Mol Hum Reprod. 2015; 21, 2330.Google Scholar
31. Igosheva, N, Abramov, AY, Poston, L, et al. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes. PLoS One. 2010; 5, e10074.CrossRefGoogle ScholarPubMed
32. Grindler, NM, Moley, KH. Maternal obesity, infertility and mitochondrial dysfunction: potential mechanisms emerging from mouse model systems. Mol Hum Reprod. 2013; 19, 486494.Google Scholar
33. Wu, LL, Russell, DL, Wong, SL, et al. Mitochondrial dysfunction in oocytes of obese mothers: transmission to offspring and reversal by pharmacological endoplasmic reticulum stress inhibitors. Development. 2015; 142, 681691.Google Scholar
34. Ge, ZJ, Luo, SM, Lin, F, et al. DNA methylation in oocytes and liver of female mice and their offspring: effects of high-fat-diet-induced obesity. Environ Health Perspect. 2014; 122, 159164.CrossRefGoogle ScholarPubMed
35. Wei, Y, Yang, CR, Wei, YP, et al. Enriched environment-induced maternal weight loss reprograms metabolic gene expression in mouse offspring. J Biol Chem. 2015; 290, 46044619.CrossRefGoogle ScholarPubMed
36. Wei, Y, Schatten, H, Sun, QY. Environmental epigenetic inheritance through gametes and implications for human reproduction. Hum Reprod Update. 2015; 21, 194208.CrossRefGoogle ScholarPubMed
37. Leary, C, Leese, HJ, Sturmey, RG. Human embryos from overweight and obese women display phenotypic and metabolic abnormalities. Hum Reprod. 2015; 30, 122132.Google Scholar
38. Bromfield, JJ, Schjenken, JE, Chin, PY, et al. Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc Natl Acad Sci U S A. 2014; 111, 22002205.Google Scholar
39. McPherson, NO, Fullston, T, Aitken, RJ, Lane, M. Paternal obesity, interventions, and mechanistic pathways to impaired health in offspring. Ann Nnutr Metab. 2014; 64, 231238.Google Scholar
40. Watkins, AJ, Sinclair, KD. Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice. Am J Physiol Heart Circ Physiol. 2014; 306, H14441452.CrossRefGoogle ScholarPubMed
41. Nicholas, LM, Rattanatray, L, Morrison, JL, et al. Maternal obesity or weight loss around conception impacts hepatic fatty acid metabolism in the offspring. Obesity (Silver Spring). 2014; 22, 16851693.Google Scholar
42. Cram, LF, Zapata, MI, Toy, EC, Baker, B 3rd. Genitourinary infections and their association with preterm labor. Am Fam Physician. 2002; 65, 241248.Google Scholar
43. Williams, CL, Teeling, JL, Perry, VH, Fleming, TP. Mouse maternal systemic inflammation at the zygote stage causes blunted cytokine responsiveness in lipopolysaccharide-challenged adult offspring. BMC Biol. 2011; 9, 49.Google Scholar
44. Brison, DR, Roberts, SA, Kimber, SJ. How should we assess the safety of IVF technologies? Reprod Biomed Online. 2013; 27, 710721.CrossRefGoogle ScholarPubMed
45. Fauser, BC, Devroey, P, Diedrich, K, et al. Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature. Reprod Biomed Online. 2014; 28, 162182.CrossRefGoogle ScholarPubMed
46. Lazaraviciute, G, Kauser, M, Bhattacharya, S, Haggarty, P. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Hum Reprod Update. 2014; 20, 840852.Google Scholar
47. Ceelen, M, van Weissenbruch, MM, Vermeiden, JP, van Leeuwen, FE, Delemarre-van de Waal, HA. Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab. 2008; 93, 16821688.Google Scholar
48. Ceelen, M, van Weissenbruch, MM, Roos, JC, et al. Body composition in children and adolescents born after in vitro fertilization or spontaneous conception. J Clin Endocrinol Metab. 2007; 92, 34173423.CrossRefGoogle ScholarPubMed
49. Ceelen, M, van Weissenbruch, MM, Prein, J, et al. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents. Hum Reprod. 2009; 24, 27882795.Google Scholar
50. Sakka, SD, Loutradis, D, Kanaka-Gantenbein, C, et al. Absence of insulin resistance and low-grade inflammation despite early metabolic syndrome manifestations in children born after in vitro fertilization. Fertil Steril. 2010; 94, 16931699.Google Scholar
51. Zandstra, H, Van Montfoort, AP, Dumoulin, JC. Does the type of culture medium used influence birthweight of children born after IVF? Hum Reprod. 2015; 30, 530542.CrossRefGoogle ScholarPubMed
52. Vergouw, CG, Kostelijk, EH, Doejaaren, E, et al. The influence of the type of embryo culture medium on neonatal birthweight after single embryo transfer in IVF. Hum Reprod. 2012; 27, 26192626.Google Scholar
53. Hart, R, Norman, RJ. The longer-term health outcomes for children born as a result of IVF treatment. Part II--Mental health and development outcomes. Hum Reprod Update. 2013; 19, 244250.Google Scholar
54. Watkins, AJ, Platt, D, Papenbrock, T, et al. Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure. Proc Natl Acad Sci U S A. 2007; 104, 54495454.Google Scholar
55. Scott, KA, Yamazaki, Y, Yamamoto, M, et al. Glucose parameters are altered in mouse offspring produced by assisted reproductive technologies and somatic cell nuclear transfer. Biol Reprod. 2010; 83, 220227.Google Scholar
56. Donjacour, A, Liu, X, Lin, W, Simbulan, R, Rinaudo, PF. In vitro fertilization affects growth and glucose metabolism in a sex-specific manner in an outbred mouse model. Biol Reprod. 2014; 90, 80.Google Scholar
57. Feuer, SK, Donjacour, A, Simbulan, RK, et al. Sexually dimorphic effect of in vitro fertilization (IVF) on adult mouse fat and liver metabolomes. Endocrinology. 2014; 155, 45544567.Google Scholar
58. Ecker, DJ, 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, 15951600.Google Scholar
59. 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, 58805885.Google Scholar
60. Strata, F, Giritharan, G, Sebastiano, FD, et al. Behavior and brain gene expression changes in mice exposed to preimplantation and prenatal stress. Reprod Sci. 2015; 22, 2330.Google Scholar
61. Banrezes, B, Sainte-Beuve, T, Canon, E, et al. Adult body weight is programmed by a redox-regulated and energy-dependent process during the pronuclear stage in mouse. PLoS One. 2011; 6, e29388.Google Scholar
62. Sinclair, KD, Young, LE, Wilmut, I, McEvoy, TG. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men. Hum Reprod. 2000; 15(Suppl. 5), 6886.Google Scholar
63. Fritz, R, Jain, C, Armant, DR. Cell signaling in trophoblast-uterine communication. Int J Dev Biol. 2014; 58, 261271.Google Scholar
64. Cantone, I, Fisher, AG. Epigenetic programming and reprogramming during development. Nat Struct Mol Biol. 2013; 20, 282289.CrossRefGoogle ScholarPubMed
65. Eckert, JJ, Porter, R, Watkins, AJ, et al. Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health. PLoS One. 2012; 7, e52791.Google Scholar
66. Lane, M, Gardner, DK. Differential regulation of mouse embryo development and viability by amino acids. J Reprod Fertil. 1997; 109, 153164.Google Scholar
67. Kaye, PL, Gardner, HG. Preimplantation access to maternal insulin and albumin increases fetal growth rate in mice. Hum Reprod. 1999; 14, 30523059.Google Scholar
68. Martin, PM, Sutherland, AE. Exogenous amino acids regulate trophectoderm differentiation in the mouse blastocyst through an mTOR-dependent pathway. Dev Biol. 2001; 240, 182193.Google Scholar
69. Martin, PM, Sutherland, AE, Van Winkle, LJ. Amino acid transport regulates blastocyst implantation. Biol Reprod. 2003; 69, 11011108.Google Scholar
70. Wang, X, Proud, CG. Nutrient control of TORC1, a cell-cycle regulator. Trends Cell Biol. 2009; 19, 260267.Google Scholar
71. Sun, C, Velazquez, MA, Marfy-Smith, S, et al. Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition. Development. 2014; 141, 11401150.Google Scholar
72. Sun, C, Denisenko, O, Sheth, B, et al. Epigenetic regulation of histone modifications and Gata6 gene expression induced by maternal diet in mouse embryoid bodies in a model of developmental programming. BMC Dev Biol. 2015; 15, 3.Google Scholar
73. Coan, PM, Vaughan, OR, McCarthy, J, et al. Dietary composition programmes placental phenotype in mice. J Physiol. 2011; 589(Pt 14), 36593670.Google Scholar
74. Velazquez, MA, Sheth, B, Marfy-Smith, S, Eckert, J, Fleming, TP Insulin and branched-chain amino acid depletion during mouse in vitro preimplantation embryo development alters postnatal growth and cardiovascular physiology. World Congress of Animal Reproduction 2014, Edinburgh, UK. Reproduction Abstracts. 2014; 1, P096.Google Scholar