Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 5/2017

01-05-2017 | Embryo Biology

Quantitative and qualitative changes of mitochondria in human preimplantation embryos

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

Published in: Journal of Assisted Reproduction and Genetics | Issue 5/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
Krisher RL, Bavister BD. Responses of oocytes and embryos to the culture environment. Theriogenology. 1998;59:103–14.CrossRef
2.
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.
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.
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.
Van Blerkom J. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 2011;11:797–813.CrossRefPubMed
6.
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.
8.
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.
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.
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.
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.
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.
14.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Gibson TC, Kubisch HM, Brenner CA. Mitochondrial DNA deletions in rhesus macaque oocytes and embryos. Mol Hum Reprod. 2005;11:785–9.CrossRefPubMed
30.
Bavister BD, Squirrell JM. Mitochondrial distribution and function in oocytes and early embryos. Hum Reprod. 2000;15 Suppl 2:189–98.CrossRefPubMed
31.
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.
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.
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.
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.
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.
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.
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.
Houghton FD. Energy metabolism of the inner cell mass and trophectoderm of the mouse blastocyst. Differentiation. 2006;74:11–8.CrossRefPubMed
39.
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.
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.
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.
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
Metadata
Title
Quantitative and qualitative changes of mitochondria in human preimplantation embryos
Authors
Shu Hashimoto
Naoharu Morimoto
Masaya Yamanaka
Hiroshi Matsumoto
Takayuki Yamochi
Hiroya Goto
Masayasu Inoue
Yoshiharu Nakaoka
Hiroaki Shibahara
Yoshiharu Morimoto
Publication date
01-05-2017
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 5/2017
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-017-0886-6

Other articles of this Issue 5/2017

Journal of Assisted Reproduction and Genetics 5/2017 Go to the issue

Genetics

Impact of the FSHB gene -211G/T polymorphism on male gonadal function

Assisted Reproduction Technologies

The association between coenzyme Q10 concentrations in follicular fluid with embryo morphokinetics and pregnancy rate in assisted reproductive techniques

Technological Innovations

Polar body transfer restores the developmental potential of oocytes to blastocyst stage in a case of repeated embryo fragmentation

Fertility Preservation

Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments

Genetics

A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family

Genetics

Association study of HNF1A in women with polycystic ovary syndrome