Rapamycin Rescues the Poor Developmental Capacity of Aged Porcine Oocytes
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Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR) expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44 h+10 μM rapamycin/24 h, 47.52±5.68) or control oocytes (44 h IVM; 42.14±4.40) significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, 22.04±5.68) (p<0.05). Rapamycin treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase (MAPK), and increased the mRNA expression of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1) compared with untreated, 24 h-aged IVM oocytes (p<0.05). Furthermore, rapamycin treatment of aged oocytes decreased reactive oxygen species (ROS) activity and DNA fragmentation (p<0.05), and downregulated the mRNA expression of mTOR compared with control or untreated aged oocytes. By contrast, rapamycin treatment of aged oocytes increased mitochondrial localization (p<0.05) and upregulated the mRNA expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1), anti-apoptosis (BCL2L1 and BIRC5; p<0.05), and development (NANOG and SOX2; p<0.05) genes, but it did not affect the mRNA expression of pro-apoptosis genes (FAS and CASP3) compared with the control. This study demonstrates that rapamycin treatment can rescue the poor developmental capacity of aged porcine oocytes.
Abstract
Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR) expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44 h+10 μM rapamycin/24 h, 47.52±5.68) or control oocytes (44 h IVM; 42.14±4.40) significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, 22.04±5.68) (p<0.05). Rapamycin treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase (MAPK), and increased the mRNA expression of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1) compared with untreated, 24 h-aged IVM oocytes (p<0.05). Furthermore, rapamycin treatment of aged oocytes decreased reactive oxygen species (ROS) activity and DNA fragmentation (p<0.05), and downregulated the mRNA expression of mTOR compared with control or untreated aged oocytes. By contrast, rapamycin treatment of aged oocytes increased mitochondrial localization (p<0.05) and upregulated the mRNA expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1), anti-apoptosis (BCL2L1 and BIRC5; p<0.05), and development (NANOG and SOX2; p<0.05) genes, but it did not affect the mRNA expression of pro-apoptosis genes (FAS and CASP3) compared with the control. This study demonstrates that rapamycin treatment can rescue the poor developmental capacity of aged porcine oocytes.
참고문헌 (41)
- Agarwal, A., "Oxidative stress and its implications in female infertility - A clinician's perspective", Reprod. Biomed. Online, 11(5), pp.641~650 (2005)
- Baird, D. T., "Fertility and ageing", Hum. Reprod. Update, 11(3), pp.261~276 (2005)
- Bjedov, I., "Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster", Cell Metab, 11, pp.35~46 (2010)
- Blagosklonny, M. V., "Aging: ROS or TOR", Cell Cycle, 7(21), pp.3344~3354 (2008)
- Chambers, I., "Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells", Cell, 113, pp.643~655 (2003)
- Dodson, M. G., "Spontaneous zona reaction in the mouse as a limiting factor for the time in which an oocyte may be fertilized", J. In Vitro Fert. Embryo Transf, 6, pp.101~106 (1989)
- Dumont, F. J., "Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin", J. Immunol, 144, pp.251~258 (1990)
- George, M. A., "The distribution of alpha- and gamma-tubulin in fresh and aged human and mouse oocytes exposed to cryoprotectant", Mol. Hum. Reprod, 2, pp.445~456 (1996)
- Guertin, D. A., "Defining the role of mTOR in cancer", Cancer Cell, 12, pp.9~22 (2007)
- Gupta, M. K., "Effect of vitrification and beta-mercaptoethanol on reactive oxygen species activity and in vitro development of oocytes vitrified before or after in vitro fertilization", Fertil. Steril, 93, pp.2602~2607 (2010)
- Harman, D., "Aging: A theory based on free radical and radiation chemistry", J. Gerontol, 11, pp.298~300 (1956)
- Harris, T. E., "TOR signaling. Science's STKE: signal transduction", knowledge Environment, 2003(212), pp.re15~ (2003)
- Harrison, D. E., "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice", Nature, 460, pp.392~395 (2009)
- Jacinto, E., "Tor signalling in bugs, brain and brawn", Nat. Rev. Mol. Cell Biol, 4, pp.117~126 (2003)
- Kaeberlein, M., "Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients", Science, 310(5751), pp.1193~1196 (2005)
- Kapahi, P., "Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway", Curr. Biol, 14, pp.885~890 (2004)
- Kenyon, C. J., "The genetics of ageing", Nature, 464, pp.504~512 (2010)
- Khurana, N.K., "Energy metabolism in preimplantation bovine embryos derived in vitro or in vivo", Biology of reproduction, 62(4), pp.847~856 (2000)
- Kikuchi, K., "Maturation", M-phase promoting factor: a regulator of aging in porcine oocytes, 2000, pp.63, 715~722
- Lee, S. E., "Modulation of autophagy influences development and apoptosis in mouse embryos developing in vitro", Mol. Reprod. Dev, 78, pp.498~509 (2011)
- Lee, S. E, "Inactivation of MAPK affects centrosome assembly, but not actin filament assembly, in mouse oocytes maturing in vitro", Mol. Reprod. Dev, 74, pp.904~911 (2007)
- Lee, S. E., "mTOR is required for asymmetric division through small GTPases in mouse oocytes", Mol. Reprod. Dev, 79, pp.356~366 (2012)
- Livak, K. J., "Analysis of relative gene expression data using real-time quantitative PCR and the 2-CT method", Methods, 25, pp.402~408 (2001)
- Luo, S., "Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and autophagy", Cell Death Differ, 14, pp.1247~1250 (2007)
- Ma, W., "Reduced expression of MAD2, BCL2, and MAP kinase activity in pig oocytes after in vitro aging are associated with defects in sister chromatid segregation during meiosis II and embryo fragmentation after activation", Biol. Reprod, 72, pp.373~383 (2005)
- Mammucari, C., "Signaling pathways in mitochondrial dysfunction and aging", Mech. Ageing Dev, 131, pp.536~543 (2010)
- Miao, Y. L., "Oocyte aging: cellular and molecular changes, developmental potential and reversal possibility", Human Reprod. Update, 15, pp.573~585 (2009)
- Mitsui, K., "The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells", Cell, 113, pp.631~642 (2003)
- Nichols, J., "Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4", Cell, 95, pp.379~391 (1998)
- Ono, T., "Offspring from intracytoplasmic sperm injection of aged mouse oocytes treated with caffeine or MG132", Genesis, 49, pp.460~471 (2011)
- Pellestor, F., "Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes", Hum. Genet, 112, pp.195~203 (2003)
- Shigenaga, M. K., "Oxidative damage and mitochondrial decay in aging", Proceedings of the National Academy of Sciences of the United States of America, 91, pp.10771~10778 (1994)
- Somfai, T., "Cytoskeletal abnormalities in relation with meiotic competence and ageing in porcine and bovine oocytes during in vitro maturation", Anat. Histol. Ebryol, 40, pp.335~344 (2011)
- Steuerwald, N. M., "Post-ovulatory aging of mouse oocytes leads to decreased MAD2 transcripts and increased frequencies of premature centromere separation and anaphase", Mol. Hum. Reprod, 11, pp.623~630 (2005)
- Sun, Q. Y., "Regulation of mitogen-activated protein kinase phosphorylation, microtubule organization, chromatin behavior, and cell cycle progression by protein phosphatases during pig oocyte maturation and fertilization in vitro", Biol. Reprod, 66, pp.580~588 (2002)
- Tarin, J.J., "Potential effects of age-associated oxidative stress on mammalian oocytes", embryos, 1996, pp.2, 717~724
- Toth, M. L., "Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans", Autophagy, 4, pp.330~338 (2008)
- Tripathi, A., "Intracellular levels of hydrogen peroxide and nitric oxide in oocytes at various stages of meiotic cell cycle and apoptosis", Free Radic. Res, 43(3), pp.287~294 (2009)
- Vellai, T., "Genetics: influence of TOR kinase on lifespan in C. elegans", Nature, 426(6967), pp.620~ (2003)
- Wullschleger, S., "TOR signaling in growth and metabolism", Cell, 124, pp.471~484 (2006)
- Xu, Z., "Spontaneous activation of ovulated mouse eggs: time-dependent effects on M-phase exit, cortical granule exocytosis, maternal messenger ribonucleic acid recruitment, and inositol 1,4,5-trisphosphate sensitivity", Biol. Reprod, 57, pp.743~750 (1997)