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The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality.
Hum Reprod. 2017 03 01; 32(3):607-614.HR

Abstract

STUDY QUESTION

Could the mitochondrial DNA (mtDNA) content of cumulus granulosa cells (CGCs) be related to oocyte competence?

SUMMARY ANSWER

The quality of embryos obtained during IVF procedures appears to be linked to mtDNA copy numbers in the CGCs.

WHAT IS KNOWN ALREADY

Oocyte quality is linked to oocyte mtDNA content in the human and other species, and the mtDNA copy number of the oocyte is related to that of the corresponding CGCs. Moreover, the quantification of CGC mtDNA has recently been proposed as a biomarker of embryo viability.

STUDY DESIGN SIZE, DURATION

An observational study was performed on 452 oocyte-cumulus complexes retrieved from 62 patients undergoing ICSI at the ART Center of the University Hospital of Angers, France, from January to May 2015.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. The relationship between CGC mtDNA content and oocyte maturity and fertilizability, on one hand, and embryo quality, on the other, was investigated using univariate and multivariate generalized models with fixed and mixed effects.

MAIN RESULTS AND THE ROLE OF CHANCE

No relationship was found between CGC mtDNA content and oocyte maturity or fertilizability. In contrast, there was a significant link between the content of mtDNA in CGCs surrounding an oocyte and the embryo quality, with significantly higher mtDNA copy numbers being associated with good quality embryos compared with fair or poor quality embryos [interquartile range, respectively, 738 (250-1228) and 342 (159-818); P = 0.006]. However, the indication provided by the quantification of CGC mtDNA concerning the eventuality of good embryo quality was seriously subject to patient effect (AUC = 0.806, 95%CI = 0.719-0.869). The quantity of CGC mtDNA was influenced by BMI and smoking.

LARGE SCALE DATA

N/A.

LIMITATIONS REASONS FOR CAUTION

The quantification of CGC mtDNA may indicate embryo quality. However, since it is affected by patient specificity, it should be used with caution. It remains to be seen whether this marker could directly predict the implantation capacity of the embryo, which is the main objective in IVF practice.

WIDER IMPLICATIONS OF THE FINDINGS

Our study suggests that the quantification of CGC mtDNA may be a novel biomarker of embryo viability. However, patient specificity makes it impossible to establish a general threshold value, valid for all patients. Nevertheless, further studies are needed to determine whether the quantification of CGC mtDNA may, in combination with the morpho-kinetic method, offer an additional criterion for selecting the best embryo for transfer from a given cohort.

STUDY FUNDING/COMPETING INTEREST(S)

This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centres INSERM and the CNRS. There were no competing interests.

Authors+Show Affiliations

Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France. PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France.Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.SFR ICAT, Université Angers, Angers, France. DRCI, Cellule Data Management, CHU Angers, Angers, France.PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France. Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.Service de Gynécologie-Obstétrique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France. PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France.Département de Biochimie et Génétique, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France. PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France.PREMMi/Pôle de Recherche et d'Enseignement en Médecine Mitochondriale, Institut MITOVASC, CNRS 6214, INSERM U1083, Université d'Angers, Angers, France. Laboratoire de Biologie de la Reproduction, Centre Hospitalier Universitaire d'Angers, 49933 Angers Cedex 9, France.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28077604

Citation

Desquiret-Dumas, V, et al. "The Mitochondrial DNA Content of Cumulus Granulosa Cells Is Linked to Embryo Quality." Human Reproduction (Oxford, England), vol. 32, no. 3, 2017, pp. 607-614.
Desquiret-Dumas V, Clément A, Seegers V, et al. The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Hum Reprod. 2017;32(3):607-614.
Desquiret-Dumas, V., Clément, A., Seegers, V., Boucret, L., Ferré-L'Hotellier, V., Bouet, P. E., Descamps, P., Procaccio, V., Reynier, P., & May-Panloup, P. (2017). The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Human Reproduction (Oxford, England), 32(3), 607-614. https://doi.org/10.1093/humrep/dew341
Desquiret-Dumas V, et al. The Mitochondrial DNA Content of Cumulus Granulosa Cells Is Linked to Embryo Quality. Hum Reprod. 2017 03 1;32(3):607-614. PubMed PMID: 28077604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. AU - Desquiret-Dumas,V, AU - Clément,A, AU - Seegers,V, AU - Boucret,L, AU - Ferré-L'Hotellier,V, AU - Bouet,P E, AU - Descamps,P, AU - Procaccio,V, AU - Reynier,P, AU - May-Panloup,P, PY - 2016/07/21/received PY - 2016/12/08/accepted PY - 2017/1/13/pubmed PY - 2018/2/23/medline PY - 2017/1/13/entrez KW - cumulus cells KW - embryo quality KW - granulosa cells KW - mitochondria KW - mitochondrial DNA SP - 607 EP - 614 JF - Human reproduction (Oxford, England) JO - Hum. Reprod. VL - 32 IS - 3 N2 - STUDY QUESTION: Could the mitochondrial DNA (mtDNA) content of cumulus granulosa cells (CGCs) be related to oocyte competence? SUMMARY ANSWER: The quality of embryos obtained during IVF procedures appears to be linked to mtDNA copy numbers in the CGCs. WHAT IS KNOWN ALREADY: Oocyte quality is linked to oocyte mtDNA content in the human and other species, and the mtDNA copy number of the oocyte is related to that of the corresponding CGCs. Moreover, the quantification of CGC mtDNA has recently been proposed as a biomarker of embryo viability. STUDY DESIGN SIZE, DURATION: An observational study was performed on 452 oocyte-cumulus complexes retrieved from 62 patients undergoing ICSI at the ART Center of the University Hospital of Angers, France, from January to May 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: The average mtDNA content of CGCs was assessed by using a quantitative real-time PCR technique. The relationship between CGC mtDNA content and oocyte maturity and fertilizability, on one hand, and embryo quality, on the other, was investigated using univariate and multivariate generalized models with fixed and mixed effects. MAIN RESULTS AND THE ROLE OF CHANCE: No relationship was found between CGC mtDNA content and oocyte maturity or fertilizability. In contrast, there was a significant link between the content of mtDNA in CGCs surrounding an oocyte and the embryo quality, with significantly higher mtDNA copy numbers being associated with good quality embryos compared with fair or poor quality embryos [interquartile range, respectively, 738 (250-1228) and 342 (159-818); P = 0.006]. However, the indication provided by the quantification of CGC mtDNA concerning the eventuality of good embryo quality was seriously subject to patient effect (AUC = 0.806, 95%CI = 0.719-0.869). The quantity of CGC mtDNA was influenced by BMI and smoking. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The quantification of CGC mtDNA may indicate embryo quality. However, since it is affected by patient specificity, it should be used with caution. It remains to be seen whether this marker could directly predict the implantation capacity of the embryo, which is the main objective in IVF practice. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that the quantification of CGC mtDNA may be a novel biomarker of embryo viability. However, patient specificity makes it impossible to establish a general threshold value, valid for all patients. Nevertheless, further studies are needed to determine whether the quantification of CGC mtDNA may, in combination with the morpho-kinetic method, offer an additional criterion for selecting the best embryo for transfer from a given cohort. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University Hospital of Angers, the University of Angers, France, and the French national research centres INSERM and the CNRS. There were no competing interests. SN - 1460-2350 UR - https://www.unboundmedicine.com/medline/citation/28077604/The_mitochondrial_DNA_content_of_cumulus_granulosa_cells_is_linked_to_embryo_quality_ L2 - https://academic.oup.com/humrep/article-lookup/doi/10.1093/humrep/dew341 DB - PRIME DP - Unbound Medicine ER -