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Blastomere Homeostasis

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ART and the Human Blastocyst

Part of the book series: Proceedings in the Serono Symposia USA Series ((SERONOSYMP))

Abstract

Cellular homeostasis is defined as the ability of the cell to regulate key processes such as intracellular levels of calcium (Ca2+i), pH (pHi), and metabolic parameters such as energy charge and redox potential. Cellular homeostasis regulates a multitude of cell functions such as cell division, protein synthesis, differentiation, cell-cell communication, cytoskeletal dynamics, and metabolism. In addition, calcium is a universal trigger for many cell functions. Changes in metabolic homeostasis (e.g., energy charge or redox potential) are also key regulators of enzyme function and therefore metabolic activity and energy production. Small changes in levels of pHi or Ca2+i can also regulate enzyme activity and energy production; therefore, it is a prerequisite for normal cell development that both ionic and metabolic homeostasis are tightly regulated. Aberrations in cellular homeostasis result in perturbed cell function and a loss in developmental competence.

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References

  1. Edwards LJ, Williams DA, Gardner DK. Intracellular pH of the preimplantation mouse embryo: effects of extracellular pH and weak acids. Mol Reprod Dev 1998;50:434–42.

    Google Scholar 

  2. Zhao Y, Chauvet PJ, Alper SL, Baltz JM. Expression and function of bicarbonate/chloride exchangers in the preimplantation mouse embryo. J Biol Chem 1995;270:24428–34.

    Google Scholar 

  3. Phillips KP, Baltz JM. Intracellular pH regulation by HC03-/Cl- exchange is activated during early mouse zygote development. Dev Biol 1999;208:392–405.

    Google Scholar 

  4. Lane M, Baltz JM, Bavister BD. Regulation of intracellular pH in hamster preimplantation embryos by the Na+/H+ antiporter. Biol Reprod 1998;59:1483–90.

    Google Scholar 

  5. Lane M, Baltz, JM, Bavister BD. Na+/H+ antiporter activity in hamster embryos is activated during fertilization. Dev Biol 1999;208:244–52.

    Google Scholar 

  6. Lane M, Bavister BD. Regulation of intracellular pH in bovine oocytes and cleavage stage embryos. Mol Reprod Dev 1999;54:396–401.

    Google Scholar 

  7. Phillips KP, Leveille MC, Claman P, Baltz JM. Intracellular pH regulation in human preimplantation embryos. Hum Reprod 2000;15:896–904.

    Google Scholar 

  8. Gibb CA, Poronnik P, Day ML, Cook DI. Control of cytosolic pH in two-cell mouse embryos: roles of H+-lactate cotransport and Na+/H+ exchange. Am J Physiol 1997;273:C404–19.

    Google Scholar 

  9. Busa WB, Nuccitelli R. Metabolic regulation via intracellular pH. Am J Physiol 1984;246:R409–38.

    Google Scholar 

  10. Leclerc C, Becker D, Buehr M, Warner A. Low intracellular pH is involved in the early embryonic death of DDK mouse eggs fertilized by alien sperm. Dev Dyn 1994;200:257–67.

    Google Scholar 

  11. Zhao Y, Baltz JM. Bicarbonate/chloride exchange and intracellular pH throughout preimplantation mouse embryo development. Am J Physiol 1996;271:C 1512–20.

    Google Scholar 

  12. Miller JGO, Schultz GA. Amino acid content of preimplantation rabbit embryos and fluids of the reproductive tract. Biol Reprod 1987;36:125.

    Google Scholar 

  13. Edwards LJ, Williams DA, Gardner DK. Intracellular pH of the mouse preimplantation embryo: amino acids act as buffers of intracellular pH. Hum Reprod 1998;13:3441–48.

    Google Scholar 

  14. Kolajora M, Baltz JM. Volume-regulated anion and organic osmolyte channels in mouse zygotes. Biol Reprod 1999;60:964–72.

    Google Scholar 

  15. Baitz JM, Biggers JD, Lechene C. Apparent absence of the Na+/H+ antiport activity in the two-cell mouse embryo. Dev Biol 1990;138:421–29.

    Google Scholar 

  16. Baltz JM, Biggers JD, Lechene C. Two-cell stage mouse embryos appear to lack mechanisms for alleviating intracellular acid loads. J Biol Chem 1991;266:6052–57.

    Google Scholar 

  17. Barr KJ, Garrill A, Jones DH, Orlowski J, Kidder GM. Contributions of Na+/H+ exchanger isofonns to preimplantation development of the mouse. Mol Reprod Dev 1998;50:146–53.

    Google Scholar 

  18. Olsnes S, Tonessen TI, Sandvig K. pH regulated anion antiport in nudeated mammalian cells. J Cell Biol 1986;102:967–71.

    Google Scholar 

  19. Lane M, Baltz JM, Bavister BD. Bicarbonate/chloride exchange regulates intracellular pH of embryos but not oocytes of the hamster. Biol Reprod 1999;61:452–57.

    Google Scholar 

  20. Johnson JD, Epel D, Paul M. Intracellular pH and activation of sea urchin eggs after fertilization. Nature 1976;262:661–64.

    Google Scholar 

  21. Dube F, Epel D. The relation between intracellular pH and rate of protein synthesis in sea urchin eggs and the existence of a pH-independent event triggered by ammonia. Exp Cell Res 1986;162:191–204.

    Google Scholar 

  22. Nuccitelli R, Webb DJ, Lagier ST, Matson GB. 31P NMR reveals increased intracellular pH after fertilization in Xenopus eggs. Proc Natl Acad Sci USA 1981;78:4421–25.

    Google Scholar 

  23. Webb DJ, Nuccitelli R. Direct measurements of intracellular pH changes in Xenopus eggs at fertilization and deavage. J Cell Biol 1981;91:562–67.

    Google Scholar 

  24. Towle DW, Baksinski A, Richard NE, Kordylewski M. Characterization of an endogenous Na+/H+ antiporter in Xenopus laevis oocytes. J Exp Biol 1991;159:359–69.

    Google Scholar 

  25. Vacquier VD. The isolation of intact cortical granules from sea urchin eggs: calcium Ions trigger granule discharge. Dev Biol 1974;43:62–74.

    Google Scholar 

  26. Grainger JL, Winkler MM, Shen SS, Steinhardt RA. Intracellular pH controls protein synthesis rate in sea urchin egg and early embryo. Dev Biol 1979;68:396–406.

    Google Scholar 

  27. Winkler MM, Steinhardt RA. Activation of protein synthesis in a sea urchin cell-free system. Dev Biol 1981;84:432–39.

    Google Scholar 

  28. Shen SS, Steinhardt RA. Direct measurement of intracellular pH during metabolic derepression of the sea urchin egg. Nature 1978;272:253–54.

    Google Scholar 

  29. Dube F, Schmidt T, Johnson CH, Epel D. The hierarchy of requirements for an elevated pHi during development of sea urchin embryos. Cell 1985;40:657–66.

    Google Scholar 

  30. Dube F, Eckberg WR. Intracellular pH increase driven by an Na+/H+ exchanger upon activation of surf dam oocytes. Dev Biol 1997;190:41–54.

    Google Scholar 

  31. Kline D, Zagray JA. Absence of an intracellular pH change following fertilization of the mouse egg. Zygote 1995;3:305–11.

    Google Scholar 

  32. Phillips KP, Baltz JM. Intracellular pH change does not accompany egg activation in the mouse. Mol Reprod Dev 1996;45:52–60.

    Google Scholar 

  33. Ben-Yosef D, Oron Y, Shalgi R. Intracellular pH of rat eggs is not affected by fertilization and the resulting calcium oscillations. Biol Reprod 1996;55:461–68.

    Google Scholar 

  34. Dale B, Menezo Y, Cohen J, DiMatteo L, Wilding M. Intracellular pH regulation in the human oocyte. Hum Reprod 1998;13:964–70.

    Google Scholar 

  35. Miyazaki S, Igusa Y. Fertilization potential in golden hamster eggs consists of recurring hyperpolarizations. Nature 1981;290:706–7.

    Google Scholar 

  36. Jones KT, Carroll J, Merriman JA, Whittingham DG, Kono T. Repetitive sperm-induced Ca2+ transients in mouse oocytes are cell cycle dependent. Development 1995;121:3259–66.

    Google Scholar 

  37. Bos-Mikich A, Whittingham DG, Jones KT. Meiotic and mitotic Ca2+ oscillations affect cell composition in resulting blastocysts. Dev Biol 1997;182:172–79.

    Google Scholar 

  38. Salustri A, Yanagishita M, Underhill CB, Laurent TC, Hascall Vc. Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle. Dev Biol 1992;151:541–51.

    Google Scholar 

  39. Laurent C, Hellstrom S, Engstrom-Laurent A, Wells AF, Bergh A. Localization and quantity of hyaluronan in urogenital organs of male and female rats. Cell Tissue Res 1995;279:241–48.

    Google Scholar 

  40. Grandin N, Charbonneau M. Cycling of intracellular free calcium and intracellular pH in Xenopus embryos: a possible role in the control of the cell cycle. J Cell Sci 1991;99:5–11.

    Google Scholar 

  41. Schatten G, Bestor T, Balczon R, Henson J, Schatten H. Intracellular pH shift leads to microtubule assembly and microtubule-mediated motility during sea urchin fertilization: correlations between elevated intracellular pH and microtubule activity and depressed intracellular pH and microtubule disassembly. Eur J Cell Biol 1985;36:116–27.

    Google Scholar 

  42. Begg DA, Rebhun LI. pH regulates the polymerization of actin in the sea urchin egg cortex. 1 Cell Biol 1979;83:241–48.

    Google Scholar 

  43. Begg DA, Wong GK, Hoyle DH, Baltz JM. Stimulation of cortical actin polymerization in the sea urchin egg cortex by NH4Cl, procaine and urethane: elevation of cytoplasmic pH is not the common mechanism of action. Cell Motil Cytoskeleton 1996;35:210–24.

    Google Scholar 

  44. Bachewich CL, Heath IB. The cytoplasmic pH influences hyphal tip growth and cytoskeleton-related organization. Fungal Genet Biol 1997;21:76–91.

    Google Scholar 

  45. Heuser J. Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH. J Cell Biol 1989;108:855–64.

    Google Scholar 

  46. Charbonneau M. The organization of the cortical endoplasmic reticulum in Xenopus eggs depends on intracellular pH: arte fact of fixation or not? Cell Differ Dev 1990;30:171–79.

    Google Scholar 

  47. Squirrell JM, Lane M, Bavister BD. Development and cellular organization in preimplantation hamster embryos are disrupted by altering intracellular pH. Dev Dyn 2001 (in press).

    Google Scholar 

  48. Yokoyama K, Kaji H, Nishimura K, Miyaji M. The role of microfilaments and microtubules during pH-regulated morphological transition in Candida albicans. Microbiology 1994;140:281–87.

    Google Scholar 

  49. Barnett DK, Bavister BD. Inhibitory effect of glucose and phosphate on the second cleavage division of hamster embryos: is it linked to metabolism? Hum Reprod 1996;11:177.

    Google Scholar 

  50. McKhann GM, Tower DB. Ammonia toxicity and cerebral oxidative metabolism. Am J Physiol 1960;200:420–24.

    Google Scholar 

  51. Danforth WH. Activation of glycolytic pathway in muscle. In: Chance B, Estabrook RW, Williamson JB, eds. Control of energy metabolism. New York: Academic Press, 1965:287–98.

    Google Scholar 

  52. Trivedi B, Danforth WH. Effect of pH on the kinetics of frog muscle phosphofructokinase. J Biol Chem 1966;241:4110–12.

    Google Scholar 

  53. Lane M, Lyons EA, Bavister BD. Cryopreservation reduces the ability of hamster 2-cell embryos to regulate intracellular pH. Hum Reprod 2000;15:389–94.

    Google Scholar 

  54. Seshagiri PB, Bavister BD. Glucose and phosphate inhibit respiration and oxidative metabolism in cultured hamster eight-cell embryos: evidence for the “Crabtree effect.” Mol Reprod Devel 1991;30:105–11.

    Google Scholar 

  55. Gardner DK. Changes in requirements and utilization of nutrients during mammalian preimplantation embryo development and their significance in embryo culture. Theriogenology 1998;49:83–102.

    Google Scholar 

  56. Nuccitelli R, Yim DL, Smart T. The sperrn-induced Ca2+ wave following fertilization of the Xenopus egg requires the production of Ins(1,4,5)P3. Dev Biol 1993;158:200–12.

    Google Scholar 

  57. Poenie M, Alderton J, Tsein RY, Steinhardt RA. Changes in free calcium with stages of the cell division cycle. Nature 1985;315:147–49.

    Google Scholar 

  58. Miyazaki S, Igusa Y. Ca-mediated activation of a K current at fertilization of golden hamster eggs. Proc Natl Acad Sci USA 1982;79:931–35.

    Google Scholar 

  59. Mitani S. The reduction of calcium current associated with early differentiation of the murine embryo. J Physiol 1985;363:71–86.

    Google Scholar 

  60. Ben-Yosef D, Oron Y, Shalgi R. Prolonged, repetitive calcium transients in rat oocytes fertilized in vitro and in vivo. FEBS Leu 1993;331:239–42.

    Google Scholar 

  61. Taylor CT, Lawerence YM, Kingsland CR, Biljan MM, Cuthbertson KSR. Oscillations in intracellular free Ca2+ induced by sperrnatozoa in human oocytes at fertilization. Hum Reprod 1993;8:2174–79.

    Google Scholar 

  62. McCorrnack JG, Halestrap AP, Denton RM. Role of calcium ions in regulation of mammalian intraitochondrial metabolism. Physiol Rev 1990;70:391–425.

    Google Scholar 

  63. Lazrak A, Peracchia C. Gap junction gating sensitivity to physiological internal calcium regardless of pH in Novikoff hepatoma cells. Biophys J 1993;65:2002–12.

    Google Scholar 

  64. Herman B. Regulation of calcium metabolism in cells. In: Anderson JJB, Garner SC, eds. “Calcium and phosphorus in health and disease.” Boca Raton: CRC Press, 1995:83–93.

    Google Scholar 

  65. Ishide N. Intracellular calcium modulators for cardiac muscle in pathological conditions. Jpn HeartJ 1996;37:1–17.

    Google Scholar 

  66. Campbell AK. Intracellular calcium: its universal role as a regulator. Chichester: John Wiley & Sons; 1983.

    Google Scholar 

  67. Eisner DA, Lederer WJ. Na-Ca exchange: stoichiometry and electrogenicity. Am J Physiol 1985;248:CI89–202.

    Google Scholar 

  68. Parratt JR. Control and manipulation of calcium movements. New York: Raven Press, 1985.

    Google Scholar 

  69. Borland RM, Biggers JD, Lechene CP, Taymour ML. Elemental composition of fluid in the human fallopian tube. J Reprod Fertil 1980;58:479–82.

    Google Scholar 

  70. Casslen B, Nilsson B. Human uterine fluid, examined in undiluted sampies for osmolarity and the concentrations of inorganic ions, albumin, glucose and urea. Am J Obstet Gynecol 1984;150:877–81.

    Google Scholar 

  71. Borland RM, Hazra S, Biggers JD, Lechene CP. The elemental composition of the environments of the gametes and preimplantation embryo during the initiation of pregnancy. Biol Reprod 1977;16:147–57.

    Google Scholar 

  72. Lane M, Boatman DE, Albrecht RM, Bavister BD. Intracellular divalent cation homeostasis and developmental competence in the hamster preimplantation embryo. Mol Reprod Dev 1998;50:443–50.

    Google Scholar 

  73. Altura BM, Altura BT, Carella A, Turlapaty PD. Ca2+ coupling in vascular smooth muscle: Mg2+ and buffer effects on contractility and membrane Ca2+ movements. Can J Physiol Pharmacol 1982;60:459–82.

    Google Scholar 

  74. Wacker WEC, Williams RJP. Magnesium/calcium balances of a biological system. J Theor Biol 1968;20:65–78.

    Google Scholar 

  75. Altura BM, Zhang A, Altura BT. Exposure of piglet coronary arterial muscle cells to low concentrations of Mg2+ found in blood of ischemic heart disease patients result in rapid elevation of cytosolic Ca2+: relevance to sudden infant death syndrome. Eur J Pharmacol 1997;338:R7-R9.

    Google Scholar 

  76. Lane M, Bavister BD. Calcium homeostasis in early hamster preimplantation embryos. Biol Reprod 1998;59:1000–7.

    Google Scholar 

  77. Kaibara M, Mitarai S, Yano KA, Kameyama M. Involvement of Na+-H+ antiporter in regulation of L-type Ca2+ channel current by angiotensin II in rabbit ventricular myocytes. Circ Res 1977;75:1121–25.

    Google Scholar 

  78. Irisawa H, Sato R. Intra and extracellular actions of proton on the calcium current of isolated guinea pig ventricular cells. Circ Res 1986;59:348–55.

    Google Scholar 

  79. Hewitson LC, Leese HJ. Energy metabolism of the trophectoderm and inner cell mass of the mouse blastocyst. J Exp Zool 1993;267:337–43.

    Google Scholar 

  80. Hewitson LC, Martin KL, Leese HJ. Effects of metabolic inhibitors on mouse preimplantation embryo development and the energy metabolism of isolated inner cell masses. Mol Reprod Dev 1996;43:323–30.

    Google Scholar 

  81. Leese HJ. Metabolism of the preimplantation mammalian embryo. In: Milligan SR, ed. Oxford Reviews of Reproductive Biology. Oxford: Oxford University Press, 1992:35.

    Google Scholar 

  82. Gardner DK, Leese HJ. Non-invasive measurement of nutrient uptake by single cultured pre-implantation mouse embryos. Hum Reprod 1986;1:25–27.

    Google Scholar 

  83. Brinster RL, Thomson JL. Development of eight-cell mouse embryos in vitro. Exp Cell Res 1966;42:308–15.

    Google Scholar 

  84. Biggers JD, Whittingham DG, Donahue RP. The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci USA 1967;58:560–67.

    Google Scholar 

  85. Leese HJ, Barton AM. Pyruvate and glucose uptake by mouse ova and preimplantation embryos. J Reprod Fertil 1984;72:9–13.

    Google Scholar 

  86. Lane M, Gardner DK. Lactate regulates pyruvate uptake and metabolism in the preimplantation mouse embryo. Biol Reprod 2000;62:16–22.

    Google Scholar 

  87. Gardner DK, Lane M, Spitzer A, Batt PA. Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells: amino acids, vitamins and culturing embryos in groups stimulate development. Biol Reprod 1994;50:390.

    Google Scholar 

  88. Rieger D, Loskutoff NM, Betteridge KJ. Developmentally related changes in the metabolism of glucose and glutamine by cattle embryos produced and co-cultured in vitro. J Reprod Fertil 1992;95:585–95.

    Google Scholar 

  89. Steeves TE, Gardner DK. Temporal and differential effects of amino acids on bovine embryo development in culture. Biol Reprod 1999;61:731–40.

    Google Scholar 

  90. Hardy K, Hooper MAK, Handyside AH, Rutherford Al, Winston RML, Leese HJ. Non-invasive measurement of glucose and pyruvate uptake by individual human oo-cytes and preimplantation embryos. Hum Reprod 1989;4:188.

    Google Scholar 

  91. Barbehenn EK, Wales RG, Lowry OH. The explanation for the blockade in glycolysis in early mouse embryos. Proc Nat Acad Sci USA 1974;71:1056.

    Google Scholar 

  92. Barbehenn EK, Wales RG, Lowry OH. Measurement of metabolites in single preimplantation embryos; a new means to study metabolic control in early embryos. J Embryol Exp Morphol 1978;43:29.

    Google Scholar 

  93. Leese HJ, Biggers JD, Mroz EA, Lechene C. Nucleotides in a single mammalian ovum or preimplantation embryo. Anal Biochem 1984;140:443–48.

    Google Scholar 

  94. Biggers JD, Gardner DK, Leese HJ. Control of carbohydrate metabolism on preimplantation embryos. In: Rosenblum IY, Heyner S, eds. Growth factors in mammalian development. Boca Raton: CRC Press, 1989:19.

    Google Scholar 

  95. Gardner DK, Leese HJ. Concentrations of nutrients in mouse oviduct fluid and their effects on embryo development and metabolism in vitro. J Reprod Fert 1990;88:361–68.

    Google Scholar 

  96. Gardner DK, Lane M. Developmental arrest is associated with altered ATP:ADP ratios and PFK activity. Biol Reprod 1997;56(Suppl. 1):216.

    Google Scholar 

  97. Denton RM, McCormack JG, Edgell NJ. Role of calcium ions in the regulation of intramitochondrial metabolism. Effects of Na+, Mg2+, and ruthenium red on the Ca2+- stimulated oxidation of oxoglutarate and on pyruvate dehydrogenase activity in intact rat heart mitochondria. Biochem J 1985;190:107–17.

    Google Scholar 

  98. Wyatt HY. Cations, enzymes and control of cell metabolism. J Theor Biol 1964;6:441–70.

    Google Scholar 

  99. Lane M, Gardner DK. EDTA stimulates development of cleavage stage mouse embryos by inhibiting the glycolytic enzyme phosphoglycerate kin ase. Biol Reprod 1997;56(Suppl. 1):193.

    Google Scholar 

  100. Cockcroft S, Gromerts BD. Activation and inhibition of calcium-dependent histamine secretion by ATP ions applied to rat mast cells. J Physiol 1979;29:222–43.

    Google Scholar 

  101. Schoolcraft WB, Gardner DK, Lane M, Schlenker T, Hamilton F, Meldrum DR. Blastocyst culture and transfer: analysis of results and parameters affecting outcome in two in vitro fertilization programs. Fertil Steril 1999;72:604–9.

    Google Scholar 

  102. Shoukir Y, Chardonnens D, Campana A, Sakkas D. Blastocyst development from supemumerary embryos after intracytoplasmic sperm injection: a paternal influence? HumReprod 1998;13:1632–37.

    Google Scholar 

  103. Ho Y, Wigglesworth K, Eppig JJ, Schultz RM. Preimplantation development of mouse embryos in KSOM: augmentation by amino acids and analysis of gene expression. Mol Reprod Dev 1995;41:232–38.

    Google Scholar 

  104. Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM. Differential effects of culture on imprinted H 19 expression in the preimplantation mouse embryo. Biol Reprod 2000;62:1526–35.

    Google Scholar 

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Authors
  1. Michelle Lane
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  2. David K. Gardner
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Editors and Affiliations

  1. Colorado Center for Reproductive Medicine, Englewood, CO, 80110, USA

    David K. Gardner D.Phil.  & Michelle Lane Ph.D.  & 

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Lane, M., Gardner, D.K. (2001). Blastomere Homeostasis. In: Gardner, D.K., Lane, M. (eds) ART and the Human Blastocyst. Proceedings in the Serono Symposia USA Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-0149-3_7

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  • DOI: https://doi.org/10.1007/978-1-4613-0149-3_7

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