Ovarian Function and Failure: The Role of the Oocyte and Its Molecules

  • Loro L. Kujjo
  • Gloria I. Perez

The ovaries are complex organs by virtue of their primary function and are also genetically unique, since they have a mixture of both somatic cells and germ cells. At birth, each ovarian germ cell or oocyte is enclosed by a specialized population of somatic (pregranulosa) cells to form the follicle, the most basic functional unit of the female gonads. Most follicles present in the ovaries of neonates exist in a state of growth arrest and are referred to as primordial follicles. Although the number of these follicles endowed in the ovaries at birth varies among species (from 2×104 to 4×104 in mice to 1×106–2×106 in humans), this stockpile of oocytes is non-renewable in all species and must provide for the entire reproductive needs of the female throughout adult life. By the age of 50 years, the ovaries in most women are exhausted and menopause ensues as a direct consequence of ovarian senescence.


Cumulus Cell Implantation Rate Primordial Follicle Mouse Oocyte Spindle Assembly Checkpoint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


25.6Glossary of Terms and Acronyms


assisted reproductive technology


adenosine 5’-triphosphate


calcium/calmodulin-dependent protein kinase II


cumulus cells


ceramide transport protein


DNA double strand breaks




endoplasmic reticulum




good-pasture antigen binding protein


in vitro fertilization


metaphase I


metaphase II


mitochondrial DNA


nicotinamide adenine dinucleotide phosphate


ovarian hyper-stimulation syndrome


premature ovarian failure


protein involved in repair of DNA.


reactive oxygen species


spindle assembly checkpoint


mitochondrial protein


  1. 1.
    Ruman J, Klein J, Sauer MV. Understanding the effects of age on female fertility. Minerva Ginecol 2003; 55:117–27.PubMedGoogle Scholar
  2. 2.
    Sauer MV. The impact of age on reproductive potential: lessons learned from oocyte donation. Maturitas 1998; 30:221–5.PubMedGoogle Scholar
  3. 3.
    Ottolenghi C, Uda M, Hamatani T, et al. Aging of oocyte, ovary, and human reproduction. Ann N Y Acad Sci 2004; 1034:117–31.PubMedGoogle Scholar
  4. 4.
    Lobo RA. Potential options for preservation of fertility in women. N Engl J Med 2005; 353:64–73.PubMedGoogle Scholar
  5. 5.
    Faddy MJ. Follicle dynamics during ovarian ageing. Mol Cell Endocrinol 2000; 163:43–8.PubMedGoogle Scholar
  6. 6.
    Gougeon A. The biological aspects of risks of infertility due to age: the female side. Rev Epidemiol Sante Publique 2005; 53:2S37–45.PubMedGoogle Scholar
  7. 7.
    Schultz GA, Heyner S. Gene expression in pre-implantation mammalian embryos. Mutat Res 1992; 296:17–31.PubMedGoogle Scholar
  8. 8.
    Latham KE, Schultz RM. Embryonic genome activation. Front Biosci 2001; 6:D748–59.PubMedGoogle Scholar
  9. 9.
    Balaban B, Urman B. Effect of oocyte morphology on embryo development and implantation. Reprod Biomed Online 2006; 12:608–15.PubMedGoogle Scholar
  10. 10.
    Choi WJ, Banerjee J, Falcone T, et al. Oxidative stress and tumor necrosis factor-alpha-induced alterations in metaphase II mouse oocyte spindle structure. Fertil Steril 2007; 81:1220–31.Google Scholar
  11. 11.
    Higdon HL 3rd, Blackhurst DW, Boone WR. Incubator management in an assisted reproductive technology laboratory. Fertil Steril 2007; 89:703–10.Google Scholar
  12. 12.
    Mikkelsen AL. Strategies in human in-vitro maturation and their clinical outcome. Reprod Biomed Online 2005; 10:593–9.PubMedGoogle Scholar
  13. 13.
    Yeung QS, Briton-Jones CM, Tjer GC, et al. The efficacy of test tube warming devices used during oocyte retrieval for IVF. J Assist Reprod Genet 2004; 21:355–60.PubMedGoogle Scholar
  14. 14.
    Fossum GT, Davidson A, Paulson RJ. Ovarian hyperstimulation inhibits embryo implantation in the mouse. J In Vitro Fert Embryo Transf 1989; 6:7–10.PubMedGoogle Scholar
  15. 15.
    Ertzeid G, Storeng R. The impact of ovarian stimulation on implantation and fetal development in mice. Hum Reprod 2001; 16:221–5.PubMedGoogle Scholar
  16. 16.
    Katz-Jaffe MG, Trounson AO, Cram DS. Chromosome 21 mosaic human preimplantation embryos predominantly arise from diploid conceptions. Fertil Steril 2005; 84:634–43.PubMedGoogle Scholar
  17. 17.
    Munne S, Magli C, Adler A, et al. Treatment-related chromosome abnormalities in human embryos. Hum Reprod 1997; 12:780–4.PubMedGoogle Scholar
  18. 18.
    Ziebe S, Lundin K, Janssens R, et al. Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF. Hum Reprod 2007; 22:2404–13.PubMedGoogle Scholar
  19. 19.
    Van der Auwera I, D'Hooghe T. Superovulation of female mice delays embryonic and fetal development. Hum Reprod 2001; 16:1237–43.PubMedGoogle Scholar
  20. 20.
    Spielmann H, Vogel R. Genotoxic and embryotoxic effects of gonadotropin hyperstimulated ovulation on murine oocytes, preimplantation embryos and term fetuses. Ann Ist Super Sanita 1993; 29:35–9.PubMedGoogle Scholar
  21. 21.
    Check JH, Choe JK, Katsoff D, et al. Controlled ovarian hyperstimulation adversely affects implantation following in vitro fertilization-embryo transfer. J Assist Reprod Genet 1999; 16:416–20.PubMedGoogle Scholar
  22. 22.
    Simon C, Cano F, Valbuena D, et al. Clinical evidence for a detrimental effect on uterine receptivity of high serum oestradiol concentrations in high and normal responder patients. Hum Reprod 1995; 10:2432–7.PubMedGoogle Scholar
  23. 23.
    Valbuena D, Martin J, de Pablo JL, et al. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril 2001;76:962–8.PubMedGoogle Scholar
  24. 24.
    van Kooij RJ, Looman CW, Habbema JD, et al. Age-dependent decrease in embryo implantation rate after in vitro fertilization. Fertil Steril 1996; 66:769–75.PubMedGoogle Scholar
  25. 25.
    Aboulghar MA, Mansour RT, Serour GI, et al. Oocyte quality in patients with severe ovarian hyperstimulation syndrome. Fertil Steril 1997; 68:1017–21.PubMedGoogle Scholar
  26. 26.
    Kok JD, Looman CW, Weima SM, et al. A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome. Fertil Steril 2006; 85: 918–24.PubMedGoogle Scholar
  27. 27.
    McKenzie LJ, Pangas SA, Carson SA, et al. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod 2004; 19:2869–74.PubMedGoogle Scholar
  28. 28.
    Assou S, Anahory T, Pantesco V, et al. The human cumulus--oocyte complex gene-expression profile. Hum Reprod 2006; 21:1705–19.PubMedGoogle Scholar
  29. 29.
    Hassan HA. Cumulus cell contribution to cytoplasmic maturation and oocyte developmental competence in vitro. J Assist Reprod Genet 2001; 18:539–43.PubMedGoogle Scholar
  30. 30.
    Ebner T, Moser M, Sommergruber M, et al. Incomplete denudation of oocytes prior to ICSI enhances embryo quality and blastocyst development. Hum Reprod 2006; 21:2972–7.PubMedGoogle Scholar
  31. 31.
    Magier S, van der Ven HH, Diedrich K, et al. Significance of cumulus oophorus in in-vitro fertilization and oocyte viability and fertility. Hum Reprod 1990; 5:847–52.PubMedGoogle Scholar
  32. 32.
    Perez GI, Tilly JL. Cumulus cells are required for the increased apoptotic potential in oocytes of aged mice. Hum Reprod 1997; 12:2781–3.PubMedGoogle Scholar
  33. 33.
    Perez GI, Jurisicova A, Matikainen T, et al. A central role for ceramide in the age-related acceleration of apoptosis in the female germline. Faseb J 2005; 19:860–2.PubMedGoogle Scholar
  34. 34.
    Jurisicova A, Lee HJ, D'Estaing SG, et al. Molecular requirements for doxorubicin-mediated death in murine oocytes. Cell Death Differ 2006; 13:1466–74.PubMedGoogle Scholar
  35. 35.
    Lopez MF. Better approaches to finding the needle in a haystack: optimizing proteome analysis through automation. Electrophoresis 2000; 21:1082–93.PubMedGoogle Scholar
  36. 36.
    Tarlatzis BC, Zepiridis L. Perimenopausal conception. Ann N Y Acad Sci 2003; 997:93–104.PubMedGoogle Scholar
  37. 37.
    Li L, Zou L. Sensing, signaling, and responding to DNA damage: organization of the checkpoint pathways in mammalian cells. J Cell Biochem 2005; 94:298–306.PubMedGoogle Scholar
  38. 38.
    Singh KK. Mitochondria damage checkpoint, aging, and cancer. Ann N Y Acad Sci 2006; 1067:182–90.PubMedGoogle Scholar
  39. 39.
    Kolesnick RN, Kronke M. Regulation of ceramide production and apoptosis. Annu Rev Physiol 1998; 60:643–65.PubMedGoogle Scholar
  40. 40.
    Cutler RG, Mattson MP. Sphingomyelin and ceramide as regulators of development and lifespan. Mech Ageing Dev 2001; 122:895–908.PubMedGoogle Scholar
  41. 41.
    Obeid LM, Hannun YA. Ceramide, stress, and a "LAG" in aging. Sci Aging Knowledge Environ 2003; 39:PE27.Google Scholar
  42. 42.
    Cutler RG, Kelly J, Storie K, et al. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proc Natl Acad Sci U S A 2004; 101:2070–5.PubMedGoogle Scholar
  43. 43.
    Ames BN, Shigenaga MK, Hagen TM. Mitochondrial decay in aging. Biochim Biophys Acta 1995;1271:165–70.PubMedGoogle Scholar
  44. 44.
    Sastre J, Borras C, Garcia-Sala D, et al. Mitochondrial damage in aging and apoptosis. Ann N Y Acad Sci 2002; 959:448–51.PubMedGoogle Scholar
  45. 45.
    Janny L, Menezo YJ. Maternal age effect on early human embryonic development and blastocyst formation. Mol Reprod Dev 1996; 45:31–7.PubMedGoogle Scholar
  46. 46.
    Jansen RP, de Boer K. The bottleneck: mitochondrial imperatives in oogenesis and ovarian follicular fate. Mol Cell Endocrinol 1998; 145:81–8.PubMedGoogle Scholar
  47. 47.
    Kirkwood TB. Ovarian ageing and the general biology of senescence. Maturitas 1998; 30:105–11.PubMedGoogle Scholar
  48. 48.
    Keefe DL. Aging and infertility in women. Med Health R I 1997; 80:403–5.PubMedGoogle Scholar
  49. 49.
    Keefe DL, Niven-Fairchild T, Powell S, et al. Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging in women. Fertil Steril 1995; 64:577–83.PubMedGoogle Scholar
  50. 50.
    Wilding M, Dale B, Marino M, et al. Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos. Hum Reprod 2001; 16:909–17.PubMedGoogle Scholar
  51. 51.
    Van Blerkom J, Davis PW, Lee J. ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum Reprod 1995; 10:415–24.PubMedGoogle Scholar
  52. 52.
    Brenner CA, Wolny YM, Barritt JA, et al. Mitochondrial DNA deletion in human oocytes and embryos. Mol Hum Reprod 1998; 4:887–92.PubMedGoogle Scholar
  53. 53.
    Barritt JA, Brenner CA, Cohen J, et al. Mitochondrial DNA rearrangements in human oocytes and embryos. Mol Hum Reprod 1999; 5:927–33.PubMedGoogle Scholar
  54. 54.
    Perez GI, Trbovich AM, Gosden RG, et al. Mitochondria and the death of oocytes. Nature 2000; 403:500–1.PubMedGoogle Scholar
  55. 55.
    Van Blerkom J, Sinclair J, Davis P. Mitochondrial transfer between oocytes: potential applications of mitochondrial donation and the issue of heteroplasmy. Hum Reprod 1998; 13: 2857–68.PubMedGoogle Scholar
  56. 56.
    Cohen J, Scott R, Alikani M, et al. Ooplasmic transfer in mature human oocytes. Mol Hum Reprod 1998; 4:269–80.PubMedGoogle Scholar
  57. 57.
    Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004; 116:205–19.PubMedGoogle Scholar
  58. 58.
    Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15:2922–33.PubMedGoogle Scholar
  59. 59.
    Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo. Curr Top Dev Biol 2007; 77:21–49.PubMedGoogle Scholar
  60. 60.
    McConnell JM, Petrie L. Mitochondrial DNA turnover occurs during preimplantation development and can be modulated by environmental factors. Reprod Biomed Online 2004; 9:418–24.PubMedGoogle Scholar
  61. 61.
    Sutovsky P, Moreno RD, Ramalho-Santos J, et al. Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biol Reprod 2000; 63:582–90.PubMedGoogle Scholar
  62. 62.
    Cummins JM. Fertilization and elimination of the paternal mitochondrial genome. Hum Reprod 2000; 15:92–101.PubMedGoogle Scholar
  63. 63.
    Thouas GA, Trounson AO, Wolvetang EJ, et al. Mitochondrial dysfunction in mouse oocytes results in preimplantation embryo arrest in vitro. Biol Reprod 2004; 71:1936–42.PubMedGoogle Scholar
  64. 64.
    Thouas GA, Trounson AO, Jones GM. Effect of female age on mouse oocyte developmental competence following mitochondrial injury. Biol Reprod 2005; 73:366–73.PubMedGoogle Scholar
  65. 65.
    Thouas GA, Trounson AO, Jones GM. Developmental effects of sublethal mitochondrial injury in mouse oocytes. Biol Reprod 2006; 74:969–77.PubMedGoogle Scholar
  66. 66.
    Manoli I, Alesci S, Blackman MR, et al. Mitochondria as key components of the stress response. Trends Endocrinol Metab 2007; 18:190–8.PubMedGoogle Scholar
  67. 67.
    Gibson TC, Kubisch HM, Brenner CA. Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Mol Hum Reprod 2005; 11:785–9.PubMedGoogle Scholar
  68. 68.
    Meng Q, Wong YT, Chen J, et al. Age-related changes in mitochondrial function and antioxidative enzyme activity in fischer 344 rats. Mech Ageing Dev 2007; 128:286–92.PubMedGoogle Scholar
  69. 69.
    Eichenlaub-Ritter U, Vogt E, Yin H, et al. Spindles, mitochondria and redox potential in ageing oocytes. Reprod Biomed Online 2004; 8:45–58.PubMedGoogle Scholar
  70. 70.
    Perez GI, Acton BM, Jurisicova A, et al. Genetic variance modifies apoptosis susceptibility in mature oocytes via alterations in DNA repair capacity and mitochondrial ultrastructure. Cell Death Differ 2007; 14:524–33.PubMedGoogle Scholar
  71. 71.
    Thorburn DR, Dahl HH. Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options. Am J Med Genet 2001; 106:102–14.PubMedGoogle Scholar
  72. 72.
    Christodoulou J. Genetic defects causing mitochondrial respiratory chain disorders and disease. Hum Reprod 2000; 15:28–43.PubMedGoogle Scholar
  73. 73.
    Acton BM, Jurisicova A, Jurisica I, et al. Alterations in mitochondrial membrane potential during preimplantation stages of mouse and human embryo development. Mol Hum Reprod 2004; 10: 23–32.PubMedGoogle Scholar
  74. 74.
    Van Blerkom J, Cox H, Davis P. Regulatory roles for mitochondria in the peri-implantation mouse blastocyst: possible origins and developmental significance of differential DeltaPsim. Reproduction 2006; 131:961–76.PubMedGoogle Scholar
  75. 75.
    Van Blerkom J. Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence. Reproduction 2004; 128: 269–80.PubMedGoogle Scholar
  76. 76.
    Takai Y, Matikainen T, Jurisicova A, et al. Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Apoptosis 2007; 12:791–800.PubMedGoogle Scholar
  77. 77.
    Takai Y, Canning J, Perez GI, et al. Bax, caspase-2, and caspase-3. are required for ovarian follicle loss caused by 4-vinylcyclohexene diepoxide exposure of female mice in vivo. Endocrinology 2003; 144:69–74.PubMedGoogle Scholar
  78. 78.
    Morita Y, Perez GI, Paris F, et al. Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy. Nat Med 2000; 6:1109–14.PubMedGoogle Scholar
  79. 79.
    Hanoux V, Pairault C, Bakalska M, et al. Caspase-2 involvement during ionizing radiation-induced oocyte death in the mouse ovary. Cell Death Differ 2007; 14:671–81.PubMedGoogle Scholar
  80. 80.
    Kim MR, Tilly JL. Current concepts in Bcl-2. family member regulation of female germ cell development and survival. Biochim Biophys Acta 2004; 1644:205–10.PubMedGoogle Scholar
  81. 81.
    Tilly JL. Commuting the death sentence: how oocytes strive to survive. Nat Rev Mol Cell Biol 2001; 2:838–48.PubMedGoogle Scholar
  82. 82.
    Nagai S, Mabuchi T, Hirata S, et al. Correlation of abnormal mitochondrial distribution in mouse oocytes with reduced developmental competence. Tohoku J Exp Med 2006; 210:137–44.PubMedGoogle Scholar
  83. 83.
    Chao HT, Lee SY, Lee HM, et al. Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries. Ann N Y Acad Sci 2005; 1042:148–56.PubMedGoogle Scholar
  84. 84.
    Tarin JJ, Perez-Albala S, Cano A. Cellular and morphological traits of oocytes retrieved from aging mice after exogenous ovarian stimulation. Biol Reprod 2001; 65:141–50.PubMedGoogle Scholar
  85. 85.
    Gardner DK, Lane M, Stevens J, et al. Noninvasive assessment of human embryo nutrient consumption as a measure of developmental potential. Fertil Steril 2001; 76:1175–80.PubMedGoogle Scholar
  86. 86.
    Swain JE, Bormann CL, Clark SG, et al. Use of energy substrates by various stage preimplantation pig embryos produced in vivo and in vitro. Reproduction 2002; 123:253–60.PubMedGoogle Scholar
  87. 87.
    Lane M, Gardner DK. Amino acids and vitamins prevent culture-induced metabolic perturbations and associated loss of viability of mouse blastocysts. Hum Reprod 1998; 13:991–7.PubMedGoogle Scholar
  88. 88.
    Krisher RL. The effect of oocyte quality on development. J Anim Sci 2004; 82:E14–23.PubMedGoogle Scholar
  89. 89.
    Nutt LK, Margolis SS, Jensen M, et al. Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell 2005; 123:89–103.PubMedGoogle Scholar
  90. 90.
    Bergeron L, Perez GI, Macdonald G, et al. Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev 1998; 12:1304–14.PubMedGoogle Scholar
  91. 91.
    Karran P. DNA double strand break repair in mammalian cells. Curr Opin Genet Dev 2000; 10:144–50.PubMedGoogle Scholar
  92. 92.
    Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett 2005; 219:125–35.PubMedGoogle Scholar
  93. 93.
    Kuznetsov S, Pellegrini M, Shuda K, et al. RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol 2007; 17:581–92.Google Scholar
  94. 94.
    Bannister LA, Pezza RJ, Donaldson JR, et al. A dominant, recombination-defective allele of Dmc1 causing male-specific sterility. PLoS Biol 2007; 5:e105.PubMedGoogle Scholar
  95. 95.
    Perez GI, Jurisicova A, Wise L, et al. Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice. Proc Natl Acad Sci U S A 2007; 104:5229–34.PubMedGoogle Scholar
  96. 96.
    Eichenlaub-Ritter U. Genetics of oocyte ageing. Maturitas 1998; 30:143–69.PubMedGoogle Scholar
  97. 97.
    Baird DT, Collins J, Egozcue J, et al. Fertility and ageing. Hum Reprod Update 2005; 11:261–76.PubMedGoogle Scholar
  98. 98.
    Thomas NS, Ennis S, Sharp AJ, et al. Maternal sex chromosome non-disjunction: evidence for X chromosome-specific risk factors. Hum Mol Genet 2001; 10:243–50.PubMedGoogle Scholar
  99. 99.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001; 2:280–91.PubMedGoogle Scholar
  100. 100.
    Hall H, Hunt P, Hassold T. Meiosis and sex chromosome aneuploidy: how meiotic errors cause aneuploidy; how aneuploidy causes meiotic errors. Curr Opin Genet Dev 2006;16: 323–9.PubMedGoogle Scholar
  101. 101.
    LeMaire-Adkins R, Radke K, Hunt PA. Lack of checkpoint control at the metaphase/anaphase transition: a mechanism of meiotic nondisjunction in mammalian females. J Cell Biol 1997; 139:1611–9.PubMedGoogle Scholar
  102. 102.
    Kouznetsova A, Lister L, Nordenskjold M, et al. Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice. Nat Genet 2007; 39:966–8.PubMedGoogle Scholar
  103. 103.
    Lightle SA, Oakley JI, Nikolova-Karakashian MN. Activation of sphingolipid turnover and chronic generation of ceramide and sphingosine in liver during aging. Mech Ageing Dev 2000; 120:111–25.PubMedGoogle Scholar
  104. 104.
    Cho W, Stahelin RV. Membrane-protein interactions in cell signaling and membrane trafficking. Annu Rev Biophys Biomol Struct 2005; 34:119–51.PubMedGoogle Scholar
  105. 105.
    Hetz CA, Hunn M, Rojas P, et al. Caspase-dependent initiation of apoptosis and necrosis by the Fas receptor in lymphoid cells: onset of necrosis is associated with delayed ceramide increase. J Cell Sci 2002; 115:4671–83.PubMedGoogle Scholar
  106. 106.
    Adam D, Heinrich M, Kabelitz D, et al. Ceramide: does it matter for T cells? Trends Immunol 2002; 23:1–4.PubMedGoogle Scholar
  107. 107.
    Okazaki T, Bielawska A, Bell RM, et al. Role of ceramide as a lipid mediator of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem 1990; 265:15823–31.PubMedGoogle Scholar
  108. 108.
    Venable ME, Webb-Froehlich LM, Sloan EF, et al. Shift in sphingolipid metabolism leads to an accumulation of ceramide in senescence. Mech Ageing Dev 2006; 127:473–80.PubMedGoogle Scholar
  109. 109.
    Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 1987; 65:1231–7.PubMedGoogle Scholar
  110. 110.
    Faddy MJ, Gosden RG, Gougeon A, et al. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 1992; 7:1342–6.PubMedGoogle Scholar
  111. 111.
    Diatlovitskaia EV, Andreasian GO, Malykh Ia N. Human ovarian ceramides and gangliosides in aging. Biokhimiia 1995; 60: 1302–6.PubMedGoogle Scholar
  112. 112.
    van Blitterswijk WJ, van der Luit AH, Caan W, et al. Sphingolipids related to apoptosis from the point of view of membrane structure and topology. Biochem Soc Trans 2001; 29: 819–24.PubMedGoogle Scholar
  113. 113.
    Hanada K, Kumagai K, Tomishige N, et al. CERT and intracellular trafficking of ceramide. Biochim Biophys Acta 2007; 1771:644–53.PubMedGoogle Scholar
  114. 114.
    Kawano M, Kumagai K, Nishijima M, et al. Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J Biol Chem 2006; 281:30279–88.PubMedGoogle Scholar
  115. 115.
    Rao RP, Yuan C, Allegood JC, et al. Ceramide transfer protein function is essential for normal oxidative stress response and lifespan. Proc Natl Acad Sci U S A 2007; 104:11364–9.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Loro L. Kujjo
    • 1
  • Gloria I. Perez
  1. 1.Department of Physiology, Biomedical and Physical SciencesMichigan State UniversityEast LansingUSA

Personalised recommendations