DOI QR코드

DOI QR Code

Adverse Effect of Superovulation Treatment on Maturation, Function and Ultrastructural Integrity of Murine Oocytes

  • Lee, Myungook (Department of Agricultural Biotechnology, Seoul National University) ;
  • Ahn, Jong Il (Research Institutes of Agriculture and Life Sciences, Seoul National University) ;
  • Lee, Ah Ran (Department of Agricultural Biotechnology, Seoul National University) ;
  • Ko, Dong Woo (Department of Agricultural Biotechnology, Seoul National University) ;
  • Yang, Woo Sub (Department of Agricultural Biotechnology, Seoul National University) ;
  • Lee, Gene (Laboratory of Molecular Genetics, Dental Research Institute, School of Dentistry, Seoul National University) ;
  • Ahn, Ji Yeon (Department of Agricultural Biotechnology, Seoul National University) ;
  • Lim, Jeong Mook (Department of Agricultural Biotechnology, Seoul National University)
  • Received : 2017.04.14
  • Accepted : 2017.07.05
  • Published : 2017.08.31

Abstract

Regular monitoring on experimental animal management found the fluctuation of ART outcome, which showed a necessity to explore whether superovulation treatment is responsible for such unexpected outcome. This study was subsequently conducted to examine whether superovulation treatment can preserve ultrastructural integrity and developmental competence of oocytes following oocyte activation and embryo culture. A randomized study using mouse model was designed and in vitro development (experiment 1), ultrastructural morphology (experiment 2) and functional integrity of the oocytes (experiment 3) retrieved after PMSG/hCG injection (superovulation group) or not (natural ovulation; control group) were evaluated. In experiment 1, more oocytes were retrieved following superovulation than following natural ovulation, but natural ovulation yielded higher (p < 0.0563) maturation rate than superovulation. The capacity of mature oocytes to form pronucleus and to develop into blastocysts in vitro was similar. In experiment 2, a notable (p < 0.0186) increase in mitochondrial deformity, characterized by the formation of vacuolated mitochondria, was detected in the superovulation group. Multivesicular body formation was also increased, whereas early endosome formation was significantly decreased. No obvious changes in other microorganelles, however, were detected, which included the formation and distribution of mitochondria, cortical granules, microvilli, and smooth and rough endoplasmic reticulum. In experiment 3, significant decreases in mitochondrial activity, ATP production and dextran uptake were detected in the superovulation group. In conclusion, superovulation treatment may change both maturational status and functional and ultrastuctural integrity of oocytes. Superovulation effect on preimplantation development can be discussed.

Keywords

artificial reproductive Technology (ART);development;gonadotrophins;microorganelle function;oocyte maturation

Acknowledgement

Supported by : National Research Foundation of Korea(NRF)

References

  1. Assey, R.J., Hyttel, P., Roche, J.F., and Boland, M. (1994). Oocyte structure and follicular steroid concentrations in superovulated versus unstimulated heifers. Mol. Reprod. Dev. 39, 8-16. https://doi.org/10.1002/mrd.1080390103
  2. Baart, E.B., Martini, E., Eijkemans, M.J., Van Opstal, D., Beckers, N.G., Verhoeff, A., Macklon, N.S., and Fauser, B.C. (2007). Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum. Reprod. 22, 980-988. https://doi.org/10.1093/humrep/del484
  3. Balaban, R.S., Nemoto, S., and Finkel, T. (2005). Mitochondria, oxidants, and aging. Cell 120, 483-495. https://doi.org/10.1016/j.cell.2005.02.001
  4. Beaumont, H.M., and Smith, A.F. (1975). Embryonic mortality during the pre- and post-implantation periods of pregnancy in mature mice after superovulation. J. Reprod. Fertil. 45, 437-448. https://doi.org/10.1530/jrf.0.0450437
  5. Burdette, J.E., Kurley, S.J., Kilen, S.M., Mayo, K.E., and Woodruff, T.K. (2006). Gonadotropin-induced superovulation drives ovarian surface epithelia proliferation in CD1 mice. Endocrinology 147, 2338-2345. https://doi.org/10.1210/en.2005-1629
  6. Byers, S.L., Payson, S.J., and Taft, R.A. (2006). Performance of ten inbred mouse strains following assisted reproductive technologies (ARTs). Theriogenology 65, 1716-1726. https://doi.org/10.1016/j.theriogenology.2005.09.016
  7. Calarco, P.G. (1995). Polarization of mitochondria in the unfertilized mouse oocyte. Dev. Genet. 16, 36-43. https://doi.org/10.1002/dvg.1020160108
  8. Chi, S., Cao, H., Wang, Y., and McNiven, M.A. (2011). Recycling of the epidermal growth factor receptor is mediated by a novel form of the clathrin adaptor protein Eps15. J. Biol. Chem. 286, 35196-35208. https://doi.org/10.1074/jbc.M111.247577
  9. Combelles, C.M., and Albertini, D.F. (2003). Assessment of oocyte quality following repeated gonadotropin stimulation in the mouse. Biol. Reprod. 68, 812-821. https://doi.org/10.1095/biolreprod.102.008656
  10. Dobrowolski, R., and De Robertis, E.M. (2011). Endocytic control of growth factor signalling: multivesicular bodies as signalling organelles. Nat. Rev. Mol. Cell Biol. 13, 53-60.
  11. Eden, E.R., White, I.J., and Futter, C.E. (2009). Down-regulation of epidermal growth factor receptor signalling within multivesicular bodies. Biochem. Soc. Trans. 37, 173-177. https://doi.org/10.1042/BST0370173
  12. Edwards, R.G., and Gates, A.H. (1959). Timing of the stages of the maturation divisions, ovulation, fertilization and the first cleavage of eggs of adult mice treated with gonadotrophins. J. Endocrinol. 18, 292-304. https://doi.org/10.1677/joe.0.0180292
  13. Eichenlaub-Ritter, U., Vogt, E., Yin, H., and Gosden, R. (2004). Spindles, mitochondria and redox potential in ageing oocytes. Reprod. Biomed. Online 8, 45-58. https://doi.org/10.1016/S1472-6483(10)60497-X
  14. Elbling, L., and Colot, M. (1985). Abnormal development and transport and increased sister-chromatid exchange in preimplantation embryos following superovulation in mice. Mutat Res 147, 189-195. https://doi.org/10.1016/0165-1161(85)90057-3
  15. Ertzeid, G., and Storeng, R. (1992). Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice. J. Reprod. Fertil. 96, 649-655. https://doi.org/10.1530/jrf.0.0960649
  16. Field, C., Li, R., and Oegema, K. (1999). Cytokinesis in eukaryotes: a mechanistic comparison. Curr. Opin. Cell Biol. 11, 68-80. https://doi.org/10.1016/S0955-0674(99)80009-X
  17. Fortier, A.L., Lopes, F.L., Darricarrere, N., Martel, J., and Trasler, J.M. (2008). Superovulation alters the expression of imprinted genes in the midgestation mouse placenta. Hum. Mol. Genet. 17, 1653-1665. https://doi.org/10.1093/hmg/ddn055
  18. Fowler, R.E., and Edwards, R.G. (1957). Induction of superovulation and pregnancy in mature mice by gonadotrophins. J. Endocrinol. 15, 374-384. https://doi.org/10.1677/joe.0.0150374
  19. Fowler, R.E., and Edwards, R.G. (1960). Effect of progesterone and oestrogen on pregnancy and embryonic mortality in adult mice following superovulation treatment. J. Endocrinol. 20, 1-8. https://doi.org/10.1677/joe.0.0200001
  20. Ghavami, M., Mohammadnejad, D., Beheshti, R., Solmani-Rad, J., and Abedelahi, A. (2015). Ultrastructural and Morphalogical Changes of Mouse Ovarian Tissues Following Direct Cover Vitrification with Different Cryoprotectants. J. Reprod. Infertil. 16, 138-147.
  21. Gras, L., McBain, J., Trounson, A., and Kola, I. (1992). The incidence of chromosomal aneuploidy in stimulated and unstimulated (natural) uninseminated human oocytes. Hum. Reprod. 7, 1396-1401. https://doi.org/10.1093/oxfordjournals.humrep.a137581
  22. Guerin, P., El Mouatassim, S., and Menezo, Y. (2001). Oxidative stress and protection against reactive oxygen species in the preimplantation embryo and its surroundings. Hum. Reprod. Update 7, 175-189. https://doi.org/10.1093/humupd/7.2.175
  23. Hamberger, L., and Wikland, M. (1993). Regulations and results concerning assisted reproduction in Sweden. J. Assist. Reprod. Genet. 10, 243-245. https://doi.org/10.1007/BF01204934
  24. Hasegawa, A., Takahashi, T., Igarashi, H., Amita, M., Matsukawa, J., and Nagase, S. (2015). Predictive factors for oocyte retrieval failure in controlled ovarian hyperstimulation protocols: a retrospective observational cohort study. Reprod. Biol. Endocrinol. 13, 53. https://doi.org/10.1186/s12958-015-0052-x
  25. Hohmann, F.P., Macklon, N.S., and Fauser, B.C. (2003). A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J. Clin. Endocrinol. Metab. 88, 166-173. https://doi.org/10.1210/jc.2002-020788
  26. Huffman, S.R., Pak, Y., and Rivera, R.M. (2015). Superovulation induces alterations in the epigenome of zygotes, and results in differences in gene expression at the blastocyst stage in mice. Mol. Reprod. Dev. 82, 207-217. https://doi.org/10.1002/mrd.22463
  27. Jang, M., Lee, E.J., Lee, S.T., Cho, M., and Lim, J.M. (2007). Preimplantation and fetal development of mouse embryos cultured in a protein-free, chemically defined medium. Fertil. Steril. 87, 445-447. https://doi.org/10.1016/j.fertnstert.2006.06.021
  28. Kalthur, G., Salian, S.R., Nair, R., Mathew, J., Adiga, S.K., Kalthur, S.G., Zeegers, D., and Hande, M.P. (2015). Distribution pattern of cytoplasmic organelles, spindle integrity, oxidative stress, octamerbinding transcription factor 4 (Oct4) expression and developmental potential of oocytes following multiple superovulation. Reprod. Fertil. Dev. doi: 10.1071/RD15184. [Epub ahead of print] https://doi.org/10.1071/RD15184
  29. Katzmann, D.J., Odorizzi, G., and Emr, S.D. (2002). Receptor downregulation and multivesicular-body sorting. Nat. Rev. Mol. Cell Biol. 3, 893-905. https://doi.org/10.1038/nrm973
  30. Kim, K.W. (2008). Visualization of micromorphology of leaf epicuticular waxes of the rubber tree Ficus elastica by electron microscopy. Micron 39, 976-984. https://doi.org/10.1016/j.micron.2007.10.006
  31. Kulkarni, G.V., Lee, W., Seth, A., and McCulloch, C.A. (1998). Role of mitochondrial membrane potential in concanavalin A-induced apoptosis in human fibroblasts. Exp. Cell Res. 245, 170-178. https://doi.org/10.1006/excr.1998.4245
  32. Labarta, E., Bosch, E., Alama, P., Rubio, C., Rodrigo, L., and Pellicer, A. (2012). Moderate ovarian stimulation does not increase the incidence of human embryo chromosomal abnormalities in in vitro fertilization cycles. J. Clin. Endocrinol. Metab. 97, E1987-1994. https://doi.org/10.1210/jc.2012-1738
  33. Legge, M., and Sellens, M.H. (1994). Optimization of superovulation in the reproductively mature mouse. J. Assist. Reprod. Genet. 11, 312-318. https://doi.org/10.1007/BF02215719
  34. Luckett, D.C., and Mukherjee, A.B. (1986). Embryonic characteristics in superovulated mouse strains. Comparative analyses of the incidence of chromosomal aberrations, morphological malformations, and mortality of embryos from two strains of superovulated mice. J. Hered. 77, 39-42. https://doi.org/10.1093/oxfordjournals.jhered.a110164
  35. Mancini, M., Anderson, B.O., Caldwell, E., Sedghinasab, M., Paty, P.B., and Hockenbery, D.M. (1997). Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line. J. Cell Biol. 138, 449-469. https://doi.org/10.1083/jcb.138.2.449
  36. Market-Velker, B.A., Zhang, L., Magri, L.S., Bonvissuto, A.C., and Mann, M.R. (2010). Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner. Hum. Mol. Genet. 19, 36-51. https://doi.org/10.1093/hmg/ddp465
  37. Miller, B.G., and Armstrong, D.T. (1981). Effects of a superovulatory dose of pregnant mare serum gonadotropin on ovarian function, serum estradiol, and progesterone levels and early embryo development in immature rats. Biol. Reprod. 25, 261-271. https://doi.org/10.1095/biolreprod25.2.261
  38. Moor, R.M., Osborn, J.C., and Crosby, I.M. (1985). Gonadotrophininduced abnormalities in sheep oocytes after superovulation. J. Reprod. Fertil. 74, 167-172. https://doi.org/10.1530/jrf.0.0740167
  39. Moore, A., Weissleder, R., and Bogdanov, A., Jr. (1997). Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages. J. Magn. Reson. Imaging 7, 1140-1145. https://doi.org/10.1002/jmri.1880070629
  40. Munoz, I., Rodriguez de Sadia, C., Gutierrez, A., Blanquez, M.J., and Pintado, B. (1994). Comparison of superovulatory response of mature outbred mice treated with FSH or PMSG and developmental potential of embryos produced. Theriogenology 41, 907-914. https://doi.org/10.1016/0093-691X(94)90506-E
  41. Nagy A, G.M., Vintersten K & Behringer T (2003). Manipulating the Mouse Embryo: A Laboratory Manual (Cold Spring Harbor).
  42. Ozturk, S., Yaba-Ucar, A., Sozen, B., Mutlu, D., and Demir, N. (2016). Superovulation alters embryonic poly(A)-binding protein (Epab) and poly(A)-binding protein, cytoplasmic 1 (Pabpc1) gene expression in mouse oocytes and early embryos. Reprod. Fertil. Dev. 28, 375-383. https://doi.org/10.1071/RD14106
  43. Plachot, M. (2003). Genetic analysis of the oocyte--a review. Placenta 24 Suppl B, S66-69. https://doi.org/10.1016/S0143-4004(03)00143-7
  44. Qin, J.Z., Pang, L.H., Li, M.Q., Xu, J., and Zhou, X. (2013). Risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology: a meta-analysis. PLoS One 8, e75953. https://doi.org/10.1371/journal.pone.0075953
  45. Salminen, A., Kaarniranta, K., Hiltunen, M., and Kauppinen, A. (2014). Krebs cycle dysfunction shapes epigenetic landscape of chromatin: novel insights into mitochondrial regulation of aging process. Cell Signal. 26, 1598-1603. https://doi.org/10.1016/j.cellsig.2014.03.030
  46. Steward, R.G., Lan, L., Shah, A.A., Yeh, J.S., Price, T.M., Goldfarb, J.M., and Muasher, S.J. (2014). Oocyte number as a predictor for ovarian hyperstimulation syndrome and live birth: an analysis of 256,381 in vitro fertilization cycles. Fertil. Steril. 101, 967-973. https://doi.org/10.1016/j.fertnstert.2013.12.026
  47. Takeuchi, T., Neri, Q.V., Katagiri, Y., Rosenwaks, Z., and Palermo, G.D. (2005). Effect of treating induced mitochondrial damage on embryonic development and epigenesis. Biol. Reprod. 72, 584-592. https://doi.org/10.1095/biolreprod.104.032391
  48. Templeton, A., and Morris, J.K. (1998). Reducing the risk of multiple births by transfer of two embryos after in vitro fertilization. N Engl. J. Med. 339, 573-577. https://doi.org/10.1056/NEJM199808273390901
  49. Van Blerkom, J. (1991). Microtubule mediation of cytoplasmic and nuclear maturation during the early stages of resumed meiosis in cultured mouse oocytes. Proc. Natl. Acad. Sci. USA 88, 5031-5035. https://doi.org/10.1073/pnas.88.11.5031
  50. Van Blerkom, J., and Runner, M.N. (1984). Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte. Am. J. Anat. 171, 335-355. https://doi.org/10.1002/aja.1001710309
  51. Van der Auwera, I., and D'Hooghe, T. (2001). Superovulation of female mice delays embryonic and fetal development. Hum. Reprod. 16, 1237-1243. https://doi.org/10.1093/humrep/16.6.1237
  52. West, M.A., Wallin, R.P., Matthews, S.P., Svensson, H.G., Zaru, R., Ljunggren, H.G., Prescott, A.R., and Watts, C. (2004). Enhanced dendritic cell antigen capture via toll-like receptor-induced actin remodeling. Science 305, 1153-1157. https://doi.org/10.1126/science.1099153
  53. Yun, Y.W., Yu, F.H., Yuen, B.H., and Moon, Y.S. (1989). Effects of a superovulatory dose of pregnant mare serum gonadotropin on follicular steroid contents and oocyte maturation in rats. Gamete Res. 23, 289-298. https://doi.org/10.1002/mrd.1120230306
  54. Ziebe, S., Bangsboll, S., Schmidt, K.L., Loft, A., Lindhard, A., and Nyboe Andersen, A. (2004). Embryo quality in natural versus stimulated IVF cycles. Hum. Reprod. 19, 1457-1460. https://doi.org/10.1093/humrep/deh264

Cited by

  1. Analysis of Protein Oxidative Modifications in Follicular Fluid from Fertile Women: Natural Versus Stimulated Cycles vol.7, pp.12, 2018, https://doi.org/10.3390/antiox7120176
  2. Embryo responses to stress induced by assisted reproductive technologies pp.1098-2795, 2019, https://doi.org/10.1002/mrd.23119
  3. Is it time to reconsider how to manage oocytes affected by smooth endoplasmic reticulum aggregates? pp.1460-2350, 2019, https://doi.org/10.1093/humrep/dez010