Skip to main content
Erschienen in: Journal of Assisted Reproduction and Genetics 5/2017

11.02.2017 | Embryo Biology

Quantitative and qualitative changes of mitochondria in human preimplantation embryos

verfasst von: Shu Hashimoto, Naoharu Morimoto, Masaya Yamanaka, Hiroshi Matsumoto, Takayuki Yamochi, Hiroya Goto, Masayasu Inoue, Yoshiharu Nakaoka, Hiroaki Shibahara, Yoshiharu Morimoto

Erschienen in: Journal of Assisted Reproduction and Genetics | Ausgabe 5/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The oxygen consumption rates (OCRs) in mice and cattle have been reported to change during preimplantation embryogenesis. On the other hand, mitochondrial DNA (mtDNA) copy number has been shown to be unchanged in mice and changed in cattle and pigs. The interactions between mitochondrial functions and mtDNA copy numbers in human embryos during preimplantation development remain obscure.

Methods

Sixteen oocytes and 100 embryos were used to assess mtDNA copy numbers and OCR. Three oocytes and 12 embryos were used to determine cytochrome c oxidase activity. All specimens were obtained between July 2004 and November 2014, and donated from couples after they had given informed consent. Mature oocytes and embryos at 2–14-cell, morula, and blastocyst stages were used to assess their OCR in the presence or absence of mitotoxins. The mtDNA copy number was determined using the samples after analysis of OCR. The relationships between developmental stages and OCR, and developmental stages and mtDNA copy number were analyzed. Furthermore, cytochrome c oxidase activity was determined in oocytes and 4-cell to blastocyst stage embryos.

Results

The structure of inner mitochondrial membranes and their respiratory function developed with embryonic growth and the mtDNA copy numbers decreased transiently compared with those of oocytes. The undifferentiated state of inner cell mass cells appears to be associated with a low OCR. On the other hand, the mtDNA copy numbers increased and aerobic metabolism of mitochondria increased in trophectoderm cells.

Conclusions

The mitochondrial respiratory function of human embryos developed along with embryonic growth although the copy numbers of mtDNA decreased transiently before blastulation. OCRs increased toward the morula stage ahead of an increase of mtDNA at the time of blastulation. Data regarding changes in mitochondrial function and mtDNA copy number during preimplantation development of human embryos will be useful for the development of ideal culture media.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Krisher RL, Bavister BD. Responses of oocytes and embryos to the culture environment. Theriogenology. 1998;59:103–14.CrossRef Krisher RL, Bavister BD. Responses of oocytes and embryos to the culture environment. Theriogenology. 1998;59:103–14.CrossRef
2.
Zurück zum Zitat Van Blerkom J, Davis P, 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.CrossRefPubMed Van Blerkom J, Davis P, 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.CrossRefPubMed
3.
Zurück zum Zitat Van Blerkom J. Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence. Reproduction. 2004;128:269–80.CrossRefPubMed Van Blerkom J. Mitochondria in human oogenesis and preimplantation embryogenesis: engines of metabolism, ionic regulation and developmental competence. Reproduction. 2004;128:269–80.CrossRefPubMed
4.
Zurück zum Zitat Stojkovic M, Machado SA, Stojkovic P, Zakhartchenko V, Hutzler P, Goncalves PB, et al. Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol Reprod. 2001;64:904–9.CrossRefPubMed Stojkovic M, Machado SA, Stojkovic P, Zakhartchenko V, Hutzler P, Goncalves PB, et al. Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol Reprod. 2001;64:904–9.CrossRefPubMed
5.
Zurück zum Zitat Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11:797–813.CrossRefPubMed Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11:797–813.CrossRefPubMed
6.
Zurück zum Zitat Dalton CM, Szabadkai G, Carroll J. Measurement of ATP in single oocytes: impact of maturation and cumulus cells on levels and consumption. J Cell Physiol. 2014;229:353–61.CrossRefPubMed Dalton CM, Szabadkai G, Carroll J. Measurement of ATP in single oocytes: impact of maturation and cumulus cells on levels and consumption. J Cell Physiol. 2014;229:353–61.CrossRefPubMed
7.
Zurück zum Zitat Wai T, Ao A, Zhang X, Cyr D, Dufort D, Shoubridge EA. The role of mitochondrial DNA copy number in mammalian fertility. Biol Reprod. 2010;83:52–62.CrossRefPubMedPubMedCentral Wai T, Ao A, Zhang X, Cyr D, Dufort D, Shoubridge EA. The role of mitochondrial DNA copy number in mammalian fertility. Biol Reprod. 2010;83:52–62.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet. 2008;40:249–54.CrossRefPubMed Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet. 2008;40:249–54.CrossRefPubMed
9.
Zurück zum Zitat May-Panloup P, Vignon X, Chrétien MF, Heyman Y, Tamassia M, Malthièry Y, et al. Increase of mitochondrial DNA content and transcripts in early bovine embryogenesis associated with upregulation of mtTFA and NRF1 transcription factors. Reprod Biol Endocrinol. 2005;3:65.CrossRefPubMedPubMedCentral May-Panloup P, Vignon X, Chrétien MF, Heyman Y, Tamassia M, Malthièry Y, et al. Increase of mitochondrial DNA content and transcripts in early bovine embryogenesis associated with upregulation of mtTFA and NRF1 transcription factors. Reprod Biol Endocrinol. 2005;3:65.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Spikings EC, Alderson J, St John JC. Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development. Biol Reprod. 2007;76:327–35.CrossRefPubMed Spikings EC, Alderson J, St John JC. Regulated mitochondrial DNA replication during oocyte maturation is essential for successful porcine embryonic development. Biol Reprod. 2007;76:327–35.CrossRefPubMed
11.
Zurück zum Zitat Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, et al. Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep. 2016;6:23229.CrossRefPubMedPubMedCentral Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, et al. Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep. 2016;6:23229.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat May-Panloup P, Chretien MF, Malthiery Y, Reynier P. Mitochondrial DNA in the oocyte and the developing embryo. Curr Top Dev Biol. 2007;77:51–83.CrossRefPubMed May-Panloup P, Chretien MF, Malthiery Y, Reynier P. Mitochondrial DNA in the oocyte and the developing embryo. Curr Top Dev Biol. 2007;77:51–83.CrossRefPubMed
13.
Zurück zum Zitat Xu B, Guo N, Zhang XM, Shi W, Tong XH, Iqbal F, et al. Oocyte quality is decreased in women with minimal or mild endometriosis. Sci Rep. 2015;5:10779.CrossRefPubMedPubMedCentral Xu B, Guo N, Zhang XM, Shi W, Tong XH, Iqbal F, et al. Oocyte quality is decreased in women with minimal or mild endometriosis. Sci Rep. 2015;5:10779.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Monnot S, Samuels DC, Hesters L, Frydman N, Gigarel N, Burlet P, et al. Mutation dependance of the mitochondrial DNA copy number in the first stages of human embryogenesis. Hum Mol Genet. 2013;22:1867–72.CrossRefPubMed Monnot S, Samuels DC, Hesters L, Frydman N, Gigarel N, Burlet P, et al. Mutation dependance of the mitochondrial DNA copy number in the first stages of human embryogenesis. Hum Mol Genet. 2013;22:1867–72.CrossRefPubMed
15.
Zurück zum Zitat Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, et al. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015;11:e1005241.CrossRefPubMedPubMedCentral Fragouli E, Spath K, Alfarawati S, Kaper F, Craig A, Michel CE, et al. Altered levels of mitochondrial DNA are associated with female age, aneuploidy, and provide an independent measure of embryonic implantation potential. PLoS Genet. 2015;11:e1005241.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Diez-Juan A, Rubio C, Marin C, Martinez S, Al-Asmar N, Riboldi M, et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015;104:534–41.CrossRefPubMed Diez-Juan A, Rubio C, Marin C, Martinez S, Al-Asmar N, Riboldi M, et al. Mitochondrial DNA content as a viability score in human euploid embryos: less is better. Fertil Steril. 2015;104:534–41.CrossRefPubMed
17.
Zurück zum Zitat Victor AR, Brake AJ, Tyndall JC, Griffin DK, Zouves CG, Barnes FL, et al. Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential. Fertil Steril. 2016. doi:10.1016/j.fertnstert.2016.09.028.PubMed Victor AR, Brake AJ, Tyndall JC, Griffin DK, Zouves CG, Barnes FL, et al. Accurate quantitation of mitochondrial DNA reveals uniform levels in human blastocysts irrespective of ploidy, age, or implantation potential. Fertil Steril. 2016. doi:10.​1016/​j.​fertnstert.​2016.​09.​028.PubMed
18.
Zurück zum Zitat Thompson JG, Partridge RJ, Houghton FD, Cox CI, Leese HJ. Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos. J Reprod Fertil. 1996;106:299–306.CrossRefPubMed Thompson JG, Partridge RJ, Houghton FD, Cox CI, Leese HJ. Oxygen uptake and carbohydrate metabolism by in vitro derived bovine embryos. J Reprod Fertil. 1996;106:299–306.CrossRefPubMed
19.
Zurück zum Zitat Trimarchi JR, Liu L, Porterfield DM, Smith PJ, Keefe DL. Oxidative phosphorylation-dependent and -independent oxygen consumption by individual preimplantation mouse embryos. Biol Reprod. 2000;62:1866–74.CrossRefPubMed Trimarchi JR, Liu L, Porterfield DM, Smith PJ, Keefe DL. Oxidative phosphorylation-dependent and -independent oxygen consumption by individual preimplantation mouse embryos. Biol Reprod. 2000;62:1866–74.CrossRefPubMed
20.
Zurück zum Zitat Ottosen LD, Hindkjaer J, Lindenberg S, Ingerslev HJ. Murine pre-embryo oxygen consumption and developmental competence. J Assist Reprod Genet. 2007;24:359–65.CrossRefPubMedPubMedCentral Ottosen LD, Hindkjaer J, Lindenberg S, Ingerslev HJ. Murine pre-embryo oxygen consumption and developmental competence. J Assist Reprod Genet. 2007;24:359–65.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Magnusson C, Hillensjo T, Hamberger L, Nilsson L. Oxygen consumption by human oocytes and blastocysts grown in vitro. Hum Reprod. 1986;1:183–4.CrossRefPubMed Magnusson C, Hillensjo T, Hamberger L, Nilsson L. Oxygen consumption by human oocytes and blastocysts grown in vitro. Hum Reprod. 1986;1:183–4.CrossRefPubMed
22.
Zurück zum Zitat Yamanaka M, Hashimoto S, Amo A, Ito-Sasaki T, Abe H, Morimoto Y. Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption. Hum Reprod. 2011;26:3366–71.CrossRefPubMed Yamanaka M, Hashimoto S, Amo A, Ito-Sasaki T, Abe H, Morimoto Y. Developmental assessment of human vitrified-warmed blastocysts based on oxygen consumption. Hum Reprod. 2011;26:3366–71.CrossRefPubMed
23.
24.
Zurück zum Zitat Hashimoto S, Nakano T, Yamagata K, Inoue M, Morimoto Y, Nakaoka Y. Multinucleation per se is not always sufficient as a marker of abnormality to decide against transferring human embryos. Fertil Steril. 2016;106:133–9.CrossRefPubMed Hashimoto S, Nakano T, Yamagata K, Inoue M, Morimoto Y, Nakaoka Y. Multinucleation per se is not always sufficient as a marker of abnormality to decide against transferring human embryos. Fertil Steril. 2016;106:133–9.CrossRefPubMed
25.
Zurück zum Zitat Kuwayama M, Vajta G, Leda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod Biomed Online. 2005;11:608–14.CrossRefPubMed Kuwayama M, Vajta G, Leda S, Kato O. Comparison of open and closed methods for vitrification of human embryos and the elimination of potential contamination. Reprod Biomed Online. 2005;11:608–14.CrossRefPubMed
26.
Zurück zum Zitat Biggers JD, Racowsky C. The development of fertilized human ova to the blastocyst stage in KSOMAA medium: is a two-step protocol necessary? Reprod Biomed Online. 2002;5:133–40.CrossRefPubMed Biggers JD, Racowsky C. The development of fertilized human ova to the blastocyst stage in KSOMAA medium: is a two-step protocol necessary? Reprod Biomed Online. 2002;5:133–40.CrossRefPubMed
27.
Zurück zum Zitat Maezawa T, Yamanaka M, Hashimoto S, Amo A, Ohgaki A, Nakaoka Y, et al. Possible selection of viable human blastocysts after vitrification by monitoring morphological changes. J Assist Reprod Genet. 2014;31:1099–104.CrossRefPubMedPubMedCentral Maezawa T, Yamanaka M, Hashimoto S, Amo A, Ohgaki A, Nakaoka Y, et al. Possible selection of viable human blastocysts after vitrification by monitoring morphological changes. J Assist Reprod Genet. 2014;31:1099–104.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Brenner CA, Wolny YM, Barritt JA, Matt DW, Munné S, Cohen J. Mitochondrial DNA deletion in human oocytes and embryos. Mol Hum Reprod. 1998;4:887–92.CrossRefPubMed Brenner CA, Wolny YM, Barritt JA, Matt DW, Munné S, Cohen J. Mitochondrial DNA deletion in human oocytes and embryos. Mol Hum Reprod. 1998;4:887–92.CrossRefPubMed
29.
Zurück zum Zitat Gibson TC, Kubisch HM, Brenner CA. Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Mol Hum Reprod. 2005;11:785–9.CrossRefPubMed Gibson TC, Kubisch HM, Brenner CA. Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Mol Hum Reprod. 2005;11:785–9.CrossRefPubMed
30.
Zurück zum Zitat Bavister BD, Squirrell JM. Mitochondrial distribution and function in oocytes and early embryos. Hum Reprod. 2000;15 Suppl 2:189–98.CrossRefPubMed Bavister BD, Squirrell JM. Mitochondrial distribution and function in oocytes and early embryos. Hum Reprod. 2000;15 Suppl 2:189–98.CrossRefPubMed
31.
Zurück zum Zitat Motta PM, Nottola SA, Makabe S, Heyn R. Mitochondrial morphology in human fetal and adult female germ cells. Hum Reprod. 2000;15((Supplt 2)):129–47.CrossRefPubMed Motta PM, Nottola SA, Makabe S, Heyn R. Mitochondrial morphology in human fetal and adult female germ cells. Hum Reprod. 2000;15((Supplt 2)):129–47.CrossRefPubMed
32.
Zurück zum Zitat Sathananthan AH, Selvaraj K, Girijashankar ML, Ganesh V, Selvaraj P, Trounson AO. From oogonia to mature oocytes: inactivation of the maternal centrosome in humans. Microsc Res Tech. 2006;69:396–407.CrossRefPubMed Sathananthan AH, Selvaraj K, Girijashankar ML, Ganesh V, Selvaraj P, Trounson AO. From oogonia to mature oocytes: inactivation of the maternal centrosome in humans. Microsc Res Tech. 2006;69:396–407.CrossRefPubMed
33.
Zurück zum Zitat Bowles EJ, Lee JH, Alberio R, Lloyd RE, Stekel D, Campbell KH, et al. Contrasting effects of in vitro fertilization and nuclear transfer on the expression of mtDNA replication factors. Genetics. 2007;176:1511–26.CrossRefPubMedPubMedCentral Bowles EJ, Lee JH, Alberio R, Lloyd RE, Stekel D, Campbell KH, et al. Contrasting effects of in vitro fertilization and nuclear transfer on the expression of mtDNA replication factors. Genetics. 2007;176:1511–26.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Ma J, Svoboda P, Schultz RM, Stein P. Regulation of zygotic gene activation in the preimplantation mouse embryo: global activation and repression of gene expression. Biol Reprod. 2001;64:1713–21.CrossRefPubMed Ma J, Svoboda P, Schultz RM, Stein P. Regulation of zygotic gene activation in the preimplantation mouse embryo: global activation and repression of gene expression. Biol Reprod. 2001;64:1713–21.CrossRefPubMed
35.
Zurück zum Zitat Stigliani S, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation. Hum Reprod. 2013;28:2652–60.CrossRefPubMed Stigliani S, Anserini P, Venturini PL, Scaruffi P. Mitochondrial DNA content in embryo culture medium is significantly associated with human embryo fragmentation. Hum Reprod. 2013;28:2652–60.CrossRefPubMed
36.
Zurück zum Zitat Houghton FD, Thompson JG, Kennedy CJ, Leese HJ. Oxygen consumption and energy metabolism of the early mouse embryo. Mol Reprod Dev. 1996;44:476–85.CrossRefPubMed Houghton FD, Thompson JG, Kennedy CJ, Leese HJ. Oxygen consumption and energy metabolism of the early mouse embryo. Mol Reprod Dev. 1996;44:476–85.CrossRefPubMed
37.
Zurück zum Zitat Guest DJ, Allen WR. Expression of cell-surface antigens and embryonic stem cell pluripotency genes in equine blastocysts. Stem Cells Dev. 2007;16:789–96.CrossRefPubMed Guest DJ, Allen WR. Expression of cell-surface antigens and embryonic stem cell pluripotency genes in equine blastocysts. Stem Cells Dev. 2007;16:789–96.CrossRefPubMed
38.
Zurück zum Zitat Houghton FD. Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst. Differentiation. 2006;74:11–8.CrossRefPubMed Houghton FD. Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst. Differentiation. 2006;74:11–8.CrossRefPubMed
39.
Zurück zum Zitat Scholtes MC, Zeilmaker GH. A prospective, randomized study of embryo transfer results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril. 1996;65:1245–8.CrossRefPubMed Scholtes MC, Zeilmaker GH. A prospective, randomized study of embryo transfer results after 3 or 5 days of embryo culture in in vitro fertilization. Fertil Steril. 1996;65:1245–8.CrossRefPubMed
40.
Zurück zum Zitat Gardner DK, Lane M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum Reprod Update. 1997;3:367–82.CrossRefPubMed Gardner DK, Lane M. Culture and selection of viable blastocysts: a feasible proposition for human IVF? Hum Reprod Update. 1997;3:367–82.CrossRefPubMed
41.
Zurück zum Zitat Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod. 1998;13:3434–40.CrossRefPubMed Gardner DK, Schoolcraft WB, Wagley L, Schlenker T, Stevens J, Hesla J. A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization. Hum Reprod. 1998;13:3434–40.CrossRefPubMed
42.
Zurück zum Zitat Jones GM, Trounson AO, Gardner DK, Kausche A, Lolatgis N, Wood C. Evolution of a culture protocol for successful blastocyst development and pregnancy. Hum Reprod. 1998;13:169–77.CrossRefPubMed Jones GM, Trounson AO, Gardner DK, Kausche A, Lolatgis N, Wood C. Evolution of a culture protocol for successful blastocyst development and pregnancy. Hum Reprod. 1998;13:169–77.CrossRefPubMed
Metadaten
Titel
Quantitative and qualitative changes of mitochondria in human preimplantation embryos
verfasst von
Shu Hashimoto
Naoharu Morimoto
Masaya Yamanaka
Hiroshi Matsumoto
Takayuki Yamochi
Hiroya Goto
Masayasu Inoue
Yoshiharu Nakaoka
Hiroaki Shibahara
Yoshiharu Morimoto
Publikationsdatum
11.02.2017
Verlag
Springer US
Erschienen in
Journal of Assisted Reproduction and Genetics / Ausgabe 5/2017
Print ISSN: 1058-0468
Elektronische ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-017-0886-6

Weitere Artikel der Ausgabe 5/2017

Journal of Assisted Reproduction and Genetics 5/2017 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.