Stem Cell Reviews and Reports

, Volume 13, Issue 4, pp 454–464 | Cite as

Blastocyst-Derived Stem Cell Populations under Stress: Impact of Nutrition and Metabolism on Stem Cell Potency Loss and Miscarriage

  • Yu Yang
  • Alan Bolnick
  • Alexandra Shamir
  • Mohammed Abdulhasan
  • Quanwen Li
  • G. C. Parker
  • Elizabeth E. Puscheck
  • D. A. Rappolee
Article
  • 424 Downloads

Abstract

Data from in vitro and in vivo models suggest that malnutrition and stress trigger adaptive responses, leading to small for gestational age (SGA) blastocysts with fewer cell numbers. These stress responses are initially adaptive, but become maladaptive with increasing stress exposures. The common stress responses of the blastocyst-derived stem cells, pluripotent embryonic and multipotent placental trophoblast stem cells (ESCs and TSCs), are decreased growth and potency, and increased, imbalanced and irreversible differentiation. SGA embryos may fail to produce sufficient antiluteolytic placental hormone to maintain corpus luteum progesterone secretion that provides nutrition at the implantation site. Myriad stress inputs for the stem cells in the embryo can occur in vitro during in vitro fertilization/assisted reproductive technology (IVF/ART) or in vivo. Paradoxically, stresses that diminish stem cell growth lead to a higher level of differentiation simultaneously which further decreases ESC or TSC numbers in an attempt to functionally compensate for fewer cells. In addition, prolonged or strong stress can cause irreversible differentiation. Resultant stem cell depletion is proposed as a cause of miscarriage via a “quiet” death of an ostensibly adaptive response of stem cells instead of a reactive, violent loss of stem cells or their differentiated progenies.

Keywords

Metabolism Embryonic stem cells Trophoblast stem cells Stress Transcription factors Potency Differentiation Proliferation 

Notes

Acknowledgements

We acknowledge funding from the Office of the Vice President for Research at Wayne State University, NIH (1R03HD061431) and the Kam Moghissi Endowed chair (EEP) and support for GCP and DR from NIH (P30 ES020957).

Compliance with Ethical Standards

Grants Support

This research was supported by grants to DAR from NIH (1R03HD061431) and from the Office of the Vice President for Research at Wayne State University.

Conflicts of Interest

The authors declare no potential conflicts of interest.

References

  1. 1.
    Macklon, N. S., Geraedts, J. P., & Fauser, B. C. (2002). Conception to ongoing pregnancy: The 'black box' of early pregnancy loss. Human Reproduction Update, 8, 333–343.CrossRefPubMedGoogle Scholar
  2. 2.
    Spencer, T. E. (2014). Early pregnancy: Concepts, challenges, and potential solutions. Animal Frontiers, 3, 48–55.CrossRefGoogle Scholar
  3. 3.
    Puscheck, E. E., Awonuga, A. O., Yang, Y., et al. (2015). Molecular biology of the stress response in the early embryo and its stem cells. Advances in Experimental Medicine and Biology, 843, 77–128.CrossRefPubMedGoogle Scholar
  4. 4.
    Rappolee, D. A., Zhou, S., Puscheck, E. E., et al. (2013). Stress responses at the endometrial-placental interface regulate labyrinthine placental differentiation from trophoblast stem cells. Reproduction, 145, R139–R155.CrossRefPubMedGoogle Scholar
  5. 5.
    Adelman, D. M., Gertsenstein, M., Nagy, A., et al. (2000). Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses. Gene Dev., 14, 3191–3203.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rosario, G. X., Konno, T., & Soares, M. J. (2008). Maternal hypoxia activates endovascular trophoblast cell invasion. Developmental Biology, 314, 362–375.CrossRefPubMedGoogle Scholar
  7. 7.
    Borman, E. D., Foster, W. G., Greenacre, M. K., et al. (2015). Stress lowers the threshold dose at which bisphenol a disrupts blastocyst implantation, in conjunction with decreased uterine closure and e-cadherin. Chemico-Biological Interactions, 237, 87–95.CrossRefPubMedGoogle Scholar
  8. 8.
    McLaren A S, M.L. Embryogenesis in mammals. New York: Elsevier; 1976.Google Scholar
  9. 9.
    Shapiro, S. S., Dyer, S. D., & Colas, A. E. (1980). Progesterone-induced glycogen accumulation in human endometrium during organ culture. American Journal of Obstetrics and Gynecology, 136, 419–425.CrossRefPubMedGoogle Scholar
  10. 10.
    Salameh, W., Helliwell, J. P., Han, G., et al. (2006). Expression of endometrial glycogen synthase kinase-3beta protein throughout the menstrual cycle and its regulation by progesterone. Molecular Human Reproduction, 12, 543–549.CrossRefPubMedGoogle Scholar
  11. 11.
    Wilcox, A. J., Baird, D. D., & Weinberg, C. R. (1999). Time of implantation of the conceptus and loss of pregnancy. The New England Journal of Medicine, 340, 1796–1799.CrossRefPubMedGoogle Scholar
  12. 12.
    Baird, D. D., Weinberg, C. R., McConnaughey, D. R., et al. (2003). Rescue of the corpus luteum in human pregnancy. Biology of Reproduction, 68, 448–456.CrossRefPubMedGoogle Scholar
  13. 13.
    Rappolee, D. A. (1999). It's not just baby's babble/babel: Recent progress in understanding the language of early mammalian development: A minireview. Molecular Reproduction and Development, 52, 234–240.CrossRefPubMedGoogle Scholar
  14. 14.
    Jones, C. J., Choudhury, R. H., & Aplin, J. D. (2015). Tracking nutrient transfer at the human maternofetal interface from 4 weeks to term. Placenta, 36, 372–380.CrossRefPubMedGoogle Scholar
  15. 15.
    Vander Heiden, M. G., Cantley, L. C., & Thompson, C. B. (2009). Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science, 324, 1029–1033.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Xie, Y., Zhou, S., Jiang, Z., et al. (2014). Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency. Stem Cell Research, 13, 478–491.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Van Blerkom, J., Cox, H., & Davis, P. (2006). Regulatory roles for mitochondria in the peri-implantation mouse blastocyst: Possible origins and developmental significance of differential DeltaPsim. Reproduction, 131, 961–976.CrossRefPubMedGoogle Scholar
  18. 18.
    Lenaz, G. (2001). The mitochondrial production of reactive oxygen species: Mechanisms and implications in human pathology. IUBMB Life, 52, 159–164.CrossRefPubMedGoogle Scholar
  19. 19.
    Rappolee, D. A., Basilico, C., Patel, Y., et al. (1994). Expression and function of FGF-4 in peri-implantation development in mouse embryos. Development, 120, 2259–2269.PubMedGoogle Scholar
  20. 20.
    Chai, N., Patel, Y., Jacobson, K., et al. (1998). FGF is an essential regulator of the fifth cell division in preimplantation mouse embryos. Developmental Biology, 198, 105–115.CrossRefPubMedGoogle Scholar
  21. 21.
    Tanaka, S., Kunath, T., Hadjantonakis, A. K., et al. (1998). Promotion of trophoblast stem cell proliferation by FGF4. Science, 282, 2072–2075.CrossRefPubMedGoogle Scholar
  22. 22.
    Knobil, E., & Neill, J. D.( 2006). Knobil and Neill's physiology of reproduction. Amsterdam; Boston: Elsevier, 2 v. (xxix, 3230 p.).Google Scholar
  23. 23.
    Roberts, R. M., Farin, C. E., & Cross, J. C. (1990). Trophoblast proteins and maternal recognition of pregnancy. Oxford Reviews of Reproductive Biology., 12, 147–180.PubMedGoogle Scholar
  24. 24.
    Cross, J. C., Werb, Z., & Fisher, S. J. (1994). Implantation and the placenta - key pieces of the development puzzle. Science, 266, 1508–1518.CrossRefPubMedGoogle Scholar
  25. 25.
    Artus, J., Kang, M., Cohen-Tannoudji, M., et al. (2013). PDGF signaling is required for primitive endoderm cell survival in the inner cell mass of the mouse blastocyst. Stem Cells, 31, 1932–1941.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Artus, J., Piliszek, A., & Hadjantonakis, A. K. (2011). The primitive endoderm lineage of the mouse blastocyst: Sequential transcription factor activation and regulation of differentiation by Sox17. Developmental Biology, 350, 393–404.CrossRefPubMedGoogle Scholar
  27. 27.
    Maunoury, R., Robine, S., Pringault, E., et al. (1988). Villin expression in the visceral endoderm and in the gut anlage during early mouse embryogenesis. The EMBO Journal, 7, 3321–3329.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Byun, K., Kim, T. K., Oh, J., et al. (2013). Heat shock instructs hESCs to exit from the self-renewal program through negative regulation of OCT4 by SAPK/JNK and HSF1 pathway. Stem Cell Research., 11, 1323–1334.CrossRefPubMedGoogle Scholar
  29. 29.
    Toh, Y. C., & Voldman, J. (2011). Fluid shear stress primes mouse embryonic stem cells for differentiation in a self-renewing environment via heparan sulfate proteoglycans transduction. The FASEB Journal, 25, 1208–1217.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yang, Y., Arenas-Hernandez, M., Gomez-Lopez, N., et al. (2016). Hypoxic stress forces irreversible differentiation of a majority of mouse trophoblast stem cells despite FGF4. Biology of Reproduction, 95, 110.CrossRefPubMedGoogle Scholar
  31. 31.
    Li, Q., Gomez-Lopez, N., Drewlo, S. et al. (2015). Development and validation of a Rex1-RFP potency activity reporter assay that quantifies stress-forced potency loss in mouse embryonic stem cells. Stem cells and development.Google Scholar
  32. 32.
    Leung, H. W., Chen, A., Choo, A. B., et al. (2011). Agitation can induce differentiation of human pluripotent stem cells in microcarrier cultures. Tissue Engineering Part C, Methods., 17, 165–172.CrossRefPubMedGoogle Scholar
  33. 33.
    Wingert, S., & Rieger, M. A. (2016). Terminal differentiation induction as DNA damage response in hematopoietic stem cells by GADD45A. Experimental Hematology., 44, 561–566.CrossRefPubMedGoogle Scholar
  34. 34.
    Wang, S., Zhou, Y., Seavey, C. N., et al. (2010). Rapid and dynamic alterations of gene expression profiles of adult porcine bone marrow-derived stem cell in response to hypoxia. Stem Cell Research., 4, 117–128.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Inomata, K., Aoto, T., Binh, N. T., et al. (2009). Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell, 137, 1088–1099.CrossRefPubMedGoogle Scholar
  36. 36.
    Slater, J. A., Zhou, S., Puscheck, E. E., et al. (2014). Stress-induced enzyme activation primes murine embryonic stem cells to differentiate toward the first extraembryonic lineage. Stem Cells and Development, 23, 3049–3064.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Awonuga, A. O., Zhong, W., Abdallah, M. E., et al. (2011). Eomesodermin, HAND1, and CSH1 proteins are induced by cellular stress in a stress-activated protein kinase-dependent manner. Molecular Reproduction and Development, 78, 519–528.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Liu, J., Xu, W., Sun, T., et al. (2009). Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation. Placenta, 30, 66–73.CrossRefPubMedGoogle Scholar
  39. 39.
    Zhong, W., Xie, Y., Wang, Y., et al. (2007). Use of hyperosmolar stress to measure stress-activated protein kinase activation and function in human HTR cells and mouse trophoblast stem cells. Reproductive Sciences, 14, 534–547.CrossRefPubMedGoogle Scholar
  40. 40.
    Xie, Y., Zhong, W., Wang, Y., et al. (2007). Using hyperosmolar stress to measure biologic and stress-activated protein kinase responses in preimplantation embryos. Molecular Human Reproduction, 13, 473–481.CrossRefPubMedGoogle Scholar
  41. 41.
    Li, Q., Yang, Y., Louden, E., et al. (2016). High throughput screens for embryonic stem cells; stress-forced potency-stemness loss enables toxicological assays. In A. Faqi (Ed.), Methods in toxicology and pharmacology. Springer.Google Scholar
  42. 42.
    Li, Q., Gomez-Lopez, N., Drewlo, S., et al. (2016). Development and validation of a Rex1-RFP potency activity reporter assay that quantifies stress-forced potency loss in mouse embryonic stem cells. Stem Cells and Development, 25, 320–328.CrossRefPubMedGoogle Scholar
  43. 43.
    Xie, Y., Awonuga, A., Liu, J., et al. (2013). Stress induces AMP-dependent loss of potency factors Id2 and Cdx2 in early embryos and stem cells. Stem Cells and Development., 22, 1564–1575.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Zhou, S., Xie, Y., Puscheck, E. E., et al. (2011). Oxygen levels that optimize TSC culture are identified by maximizing growth rates and minimizing stress. Placenta, 32, 475–481.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Simmons, D. G., Fortier, A. L., & Cross, J. C. (2007). Diverse subtypes and developmental origins of trophoblast giant cells in the mouse placenta. Developmental Biology, 304, 567–578.CrossRefPubMedGoogle Scholar
  46. 46.
    Riley, P., Anson-Cartwright, L., & Cross, J. C. (1998). The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nature Genetics, 18, 271–275.CrossRefPubMedGoogle Scholar
  47. 47.
    Xie, Y., Abdallah, M. E., Awonuga, A. O., et al. (2010). Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells. Molecular Reproduction and Development, 77, 533–539.CrossRefPubMedGoogle Scholar
  48. 48.
    Wu, G. M., Gentile, L., Fuchikami, T., et al. (2010). Initiation of trophectoderm lineage specification in mouse embryos is independent of Cdx2. Development, 137, 4159–4169.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Janatpour, M. J., McMaster, M. T., Genbacev, O., et al. (2000). Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration. Development, 127, 549–558.PubMedGoogle Scholar
  50. 50.
    Cross, J. C., Flannery, M. L., Blanar, M. A., et al. (1995). Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development, 121, 2513–2523.PubMedGoogle Scholar
  51. 51.
    Kwong, W. Y., Wild, A. E., Roberts, P., et al. (2000). Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development, 127, 4195–4202.PubMedGoogle Scholar
  52. 52.
    Sun, C., Velazquez, M. A., Marfy-Smith, S., et al. (2014). Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition. Development, 141, 1140–1150.CrossRefPubMedGoogle Scholar
  53. 53.
    Zhong, W., Xie, Y., Abdallah, M., et al. (2010). Cellular stress causes reversible, PRKAA1/2-, and proteasome-dependent ID2 protein loss in trophoblast stem cells. Reproduction, 140, 921–930.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Anderson, P., & Kedersha, N. (2008). Stress granules: The Tao of RNA triage. Trends in Biochemical Sciences, 33, 141–150.CrossRefPubMedGoogle Scholar
  55. 55.
    McEwen, E., Kedersha, N., Song, B., et al. (2005). Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposure. The Journal of Biological Chemistry, 280, 16925–16933.CrossRefPubMedGoogle Scholar
  56. 56.
    Chakraborty, D., Cui, W., Rosario, G. X., et al (2016) HIF-KDM3A-MMP12 regulatory circuit circuit ensures trophoblast plasticity and placental adaptations to hypoxia. Proceedings of the National Academy, 113(46):E7212–E7221.Google Scholar
  57. 57.
    Barker, D. J., & Osmond, C. (1986). Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet, 1, 1077–1081.CrossRefPubMedGoogle Scholar
  58. 58.
    Maekawa, M., Owada, Y., & Yoshikawa, T. (2011). Role of polyunsaturated fatty acids and fatty acid binding protein in the pathogenesis of schizophrenia. Current Pharmaceutical Design, 17, 168–175.CrossRefPubMedGoogle Scholar
  59. 59.
    Kyle, U. G., & Pichard, C. (2006). The Dutch famine of 1944-1945: A pathophysiological model of long-term consequences of wasting disease. Current Opinion in Clinical Nutrition and Metabolic Care, 9, 388–394.CrossRefPubMedGoogle Scholar
  60. 60.
    de Rooij, S. R., Painter, R. C., Phillips, D. I., et al. (2006). Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care, 29, 1897–1901.CrossRefPubMedGoogle Scholar
  61. 61.
    de Rooij, S. R., Wouters, H., Yonker, J. E., et al. (2010). Prenatal undernutrition and cognitive function in late adulthood. Proceedings of the National Academy of Sciences of the United States of America., 107, 16881–16886.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Entringer, S., Buss, C., Andersen, J., et al. (2011). Ecological momentary assessment of maternal cortisol profiles over a multiple-day period predicts the length of human gestation. Psychosomatic Medicine, 73, 469–474.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Kinsella, M. T., & Monk, C. (2009). Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clinical Obstetrics and Gynecology, 52, 425–440.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Leese, H. J., Baumann, C. G., Brison, D. R., et al. (2008). Metabolism of the viable mammalian embryo: Quietness revisited. Molecular Human Reproduction, 14, 667–672.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Wyman, A., Pinto, A. B., Sheridan, R., et al. (2008). One-cell zygote transfer from diabetic to nondiabetic mouse results in congenital malformations and growth retardation in offspring. Endocrinology, 149, 466–469.CrossRefPubMedGoogle Scholar
  66. 66.
    Chung, S., Dzeja, P. P., Faustino, R. S., et al. (2007). Mitochondrial oxidative metabolism is required for the cardiac differentiation of stem cells. Nature Clinical Practice. Cardiovascular Medicine, 4(Suppl 1), S60–S67.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Dzeja, P. P., Chung, S., Faustino, R. S., et al. (2011). Developmental enhancement of adenylate kinase-AMPK metabolic signaling axis supports stem cell cardiac differentiation. PloS One, 6, e19300.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Copp, A. J. (1995). Death before birth: Clues from gene knockouts and mutations. Trends in Genetics, 11, 87–93.CrossRefPubMedGoogle Scholar
  69. 69.
    Li, A., Chandrakanthan, V., Chami, O., et al. (2007). Culture of zygotes increases TRP53 [corrected] expression in B6 mouse embryos, which reduces embryo viability. Biology of Reproduction, 76, 362–367.CrossRefPubMedGoogle Scholar
  70. 70.
    Momand, J., Wu, H. H., & Dasgupta, G. (2000). MDM2--master regulator of the p53 tumor suppressor protein. Gene, 242, 15–29.CrossRefPubMedGoogle Scholar
  71. 71.
    de Montes, O. L. R., Wagner, D. S., & Lozano, G. (1995). Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature, 378, 203–206.CrossRefGoogle Scholar
  72. 72.
    Jones, S. N., Roe, A. E., Donehower, L. A., et al. (1995). Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature, 378, 206–208.CrossRefPubMedGoogle Scholar
  73. 73.
    Keim, A. L., Chi, M. M., & Moley, K. H. (2001). Hyperglycemia-induced apoptotic cell death in the mouse blastocyst is dependent on expression of p53. Molecular Reproduction and Development, 60, 214–224.CrossRefPubMedGoogle Scholar
  74. 74.
    Sadeu, J. C., Hughes, C. L., Agarwal, S., et al. (2010). Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: Reproductive health consequences and clinical implications. Critical Reviews in Toxicology., 40, 633–652.CrossRefPubMedGoogle Scholar
  75. 75.
    Liu, L., Cash, T. P., Jones, R. G., et al. (2006). Hypoxia-induced energy stress regulates mRNA translation and cell growth. Molecular Cell, 21, 521–531.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Wale, P. L., & Gardner, D. K. (2013) Oxygen affects the ability of mouse blastocysts to regulate ammonium. Biol Reprod.Google Scholar
  77. 77.
    He, Y., Hakvoort, T. B., Vermeulen, J. L., et al. (2007). Glutamine synthetase is essential in early mouse embryogenesis. Developmental Dynamics, 236, 1865–1875.CrossRefPubMedGoogle Scholar
  78. 78.
    Abecia, J. A., Forcada, F., Palacin, I., et al. (2015). Undernutrition affects embryo quality of superovulated ewes. Zygote, 23, 116–124.CrossRefPubMedGoogle Scholar
  79. 79.
    Carro, E., Pinilla, L., Seoane, L. M., et al. (1997). Influence of endogenous leptin tone on the estrous cycle and luteinizing hormone pulsatility in female rats. Neuroendocrinology, 66, 375–377.CrossRefPubMedGoogle Scholar
  80. 80.
    Nagatani, S., Bucholtz, D. C., Murahashi, K., et al. (1996). Reduction of glucose availability suppresses pulsatile luteinizing hormone release in female and male rats. Endocrinology, 137, 1166–1170.CrossRefPubMedGoogle Scholar
  81. 81.
    Chen, P. Y., Ganguly, A., Rubbi, L., et al. (2013). Intrauterine calorie restriction affects placental DNA methylation and gene expression. Physiological Genomics, 45, 565–576.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Gabory, A., Ferry, L., Fajardy, I., et al. (2012). Maternal diets trigger sex-specific divergent trajectories of gene expression and epigenetic systems in mouse placenta. PloS One, 7, e47986.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Gheorghe, C. P., Goyal, R., Holweger, J. D., et al. (2009). Placental gene expression responses to maternal protein restriction in the mouse. Placenta, 30, 411–417.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Bhasin, K. K., van Nas, A., Martin, L. J., et al. (2009). Maternal low-protein diet or hypercholesterolemia reduces circulating essential amino acids and leads to intrauterine growth restriction. Diabetes, 58, 559–566.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Watkins, A. J., Lucas, E. S., Marfy-Smith, S., et al. (2015). Maternal nutrition modifies trophoblast giant cell phenotype and fetal growth in mice. Reproduction, 149, 563–575.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Kawamura, K., Sato, N., Fukuda, J., et al. (2002). Leptin promotes the development of mouse preimplantation embryos in vitro. Endocrinology, 143, 1922–1931.CrossRefPubMedGoogle Scholar
  87. 87.
    Bolnick, A., Abdulhasan, M., Kilburn, B., et al. (2016) Commonly used fertility drugs, a diet supplement, and stress force AMPK-dependent block of stemness and development in cultured mammalian embryos. Journal of assisted reproduction and genetics. Google Scholar
  88. 88.
    Burkus, J., Cikos, S., Fabian, D., et al. (2013). Maternal restraint stress negatively influences growth capacity of preimplantation mouse embryos. General Physiology and Biophysics, 32, 129–137.CrossRefPubMedGoogle Scholar
  89. 89.
    Wallace, J. M., Aitken, R. P., Milne, J. S., et al. (2004) Nutritionally-mediated placental growth restriction in the growing adolescent: Consequences for the fetus. Biology of Reproduction. Google Scholar
  90. 90.
    Wallace, J., Bourke, D., Da Silva, P., et al. (2001). Nutrient partitioning during adolescent pregnancy. Reproduction, 122, 347–357.CrossRefPubMedGoogle Scholar
  91. 91.
    Wallace, J. M., Bourke, D. A., Da Silva, P., et al. (2003). Influence of progesterone supplementation during the first third of pregnancy on fetal and placental growth in overnourished adolescent ewes. Reproduction, 126, 481–487.CrossRefPubMedGoogle Scholar
  92. 92.
    Scholl TO, Hediger, M. L., Schall, J. I., et al. (1994). Maternal growth during pregnancy and the competition for nutrients. The American Journal of Clinical Nutrition., 60, 183–188.PubMedGoogle Scholar
  93. 93.
    Wallace JM, Luther JS, Milne JS et al. (2006) Nutritional modulation of adolescent pregnancy outcome -- a review. Placenta. 27 Suppl A:S61–S68.Google Scholar
  94. 94.
    Carey, B. W., Finley, L. W., Cross, J. R., et al. (2015). Intracellular alpha-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature, 518, 413–416.CrossRefPubMedGoogle Scholar
  95. 95.
    Vastenhouw, N. L., & Schier, A. F. (2012). Bivalent histone modifications in early embryogenesis. Current Opinion in Cell Biology, 24, 374–386.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Li, Q., Louden, E., Dai, J., et al. (2017). Stress forces first lineage differentiation of mouse ESCs, validation of a high throughput screen for toxicant stress. Submitted: Development.Google Scholar
  97. 97.
    Duch, A., Felipe-Abrio, I., Barroso, S., et al. (2013). Coordinated control of replication and transcription by a SAPK protects genomic integrity. Nature, 493, 116–119.CrossRefPubMedGoogle Scholar
  98. 98.
    de Nadal, E., Ammerer, G., & Posas, F. (2011). Controlling gene expression in response to stress. Nature Reviews. Genetics, 12, 833–845.PubMedGoogle Scholar
  99. 99.
    Cai, X., Hu, X., Tan, X., et al. (2015). Metformin induced AMPK activation, G0/G1 phase cell cycle arrest and the inhibition of growth of esophageal squamous cell carcinomas in vitro and in vivo. PloS One, 10, e0133349.CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Igata, M., Motoshima, H., Tsuruzoe, K., et al. (2005). Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circulation Research, 97, 837–844.CrossRefPubMedGoogle Scholar
  101. 101.
    Pauklin, S., & Vallier, L. (2013). The cell-cycle state of stem cells determines cell fate propensity. Cell, 155, 135–147.CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Jang, J., Wang, Y., Lalli, M. A., et al. (2016). Primary cilium-autophagy-Nrf2 (PAN) Axis activation commits human embryonic stem cells to a Neuroectoderm fate. Cell, 165, 410–420.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Yu Yang
    • 1
    • 2
  • Alan Bolnick
    • 1
  • Alexandra Shamir
    • 3
  • Mohammed Abdulhasan
    • 1
  • Quanwen Li
    • 1
    • 4
  • G. C. Parker
    • 4
    • 5
  • Elizabeth E. Puscheck
    • 1
  • D. A. Rappolee
    • 1
    • 2
    • 4
    • 6
  1. 1.CS Mott Center for Human Growth and Development, Department of Ob/Gyn, Reproductive Endocrinology and InfertilityWayne State University School of MedicineDetroitUSA
  2. 2.Program for Reproductive Sciences and Department of PhysiologyWayne State University School of MedicineDetroitUSA
  3. 3.University of UtahSalt Lake CityUSA
  4. 4.Institutes for Environmental Health ScienceWayne state University School of MedicineDetroitUSA
  5. 5.Department of Pediatrics and Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA
  6. 6.Department of BiologyUniversity of WindsorWindsorCanada

Personalised recommendations