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Mitochondrial and Cardiovascular Physiopathology | UMR Inserm U1083 - CNRS 6015

Separated by coma

Mitochondria and Reproduction

 

Pascale May-Panloup, University Professor-Hospital Practitioner

 

pascale.may-panloup @ univ-angers.fr

 

 

 

 

Magalie Boguenet, PhD Engineer

 

magalie.boguenet @ univ-angers.fr

 

 

 

State of the art and objectives

Mitochondria are directly involved in many cellular functions such as energy production. They have the particularity to possess their own genome, the mitochondrial DNA (mtDNA), which is maternally transmitted. Recently, much attention has been focused on the role the mtDNA plays in reproduction, evidencing links between mitochondrial function mtDNA copy number and sperm quality. Mitochondria and his genome are recognized as essential to spermatozoa, but their exact pathophysiological role and their functioning are complex and still debated.

Moreover, progresses have been made in determining the role of mitochondria with respect to oocyte maturation, fertilization and embryo development. Mitochondrial dysfunctions have also been found in various infertility related pathologies such as ovarian ageing and endometriosis. Lastly, mtDNA content of granulosa cells and trophoectoderm, and free mtDNA in embryo culture medium, are explored as biomarkers of oocyte competence and embryo viability with the aim to improve Assisted Reproductive Technologies efficiency. Over the last 15 years, we have contributed to this field by the publication of several articles on the theme of “Mitochondria and Reproduction” and various projects are in progress.

Main results from the last 5 years

We are interested on the role of mitochondria in ovarian ageing and oocyte quality:

  • Using deep sequencing, we demonstrated that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing (2017).
  • We also found in cumulus cells a relationship between the decrease of ovarian reserve and mitochondrial biogenesis (2015)
  • We have proposed that the quantification of mtDNA in cumulus cells can serve as a biomarker of embryonic quality (2017) and of embryo implantation (2018).
  • Using a murine model, we demonstrated a dysregulation of mtDNA kinetics in early embryogenesis during ageing (2019)

We are interested on the role of mitochondria in male infertility:

  • We have shown a specific metabolomic signature of seminal plasma in severe oligo-asthenospermic men. Our signature includes several metabolic changes with different impacts on sperm quality (2020).
  • In a review, we have summarized the available literature on mitochondria in spermatozoa, and, in particular, that with respect to humans, with the perspective of better understanding the anomalies that could be implicated in male infertility (2021).
  • Using next-generation sequencing, we have investigated the integrality of mitochondrial genome of spermatozoa of infertile and fertile men. We have shown that sperm mtDNA is the site of numerous rearrangements affecting paradoxically more normal spermatozoa that also contain a reduced mtDNA copy number. The increased frequency of mtDNA rearrangements in the most fertile spermatozoa is a novel result that brings a new vision to the debate about the relationship between sperm quality and mtDNA (2021).

 People involved

  • Seniors: Pascal Reynier, Pascale May-Panloup, Lisa Boucret.
  • Students:, Arthur Clément, Alexis Taugourdeau, , Pauline Teixeira, Jeanne Dasty.
  • Engineers : Valérie Desquiret-Dumas, Magalie Boguenet.

 Main publications and patents from the 5 last years

  •  Boucret, L.; Chao de la Barca, J. M.; Morinière, C.; Desquiret, V.; Ferré-L'Hôtellier, V.; Descamps, P.; Marcaillou, C.; Reynier, P.; Procaccio, V.; May-Panloup, P. Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells. Hum Reprod 2015, 30 (7), 1653-64.
  • May-Panloup, P.; Boucret, L.; Chao de la Barca, J. M.; Desquiret-Dumas, V.; Ferré-L'Hotellier, V.; Morinière, C.; Descamps, P.; Procaccio, V.; Reynier, P. Ovarian ageing: the role of mitochondria in oocytes and follicles. Hum Reprod Update 2016, 22 (6), 725-743.
  • 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. The mitochondrial DNA content of cumulus granulosa cells is linked to embryo quality. Hum Reprod 2017, 32(3) :607-614.
  • Boucret, L., Bris, C., Seegers, V., Goudenège, D., Desquiret-Dumas, V., Domin-Bernhard, M., Ferré-L’Hotellier, V., Bouet, P.E., Descamps, P., Reynier, P., Procaccio, V., and May-Panloup, P. Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing. Hum Reprod 2017, 32(10), 2101-2109.
  • Chao de la Barca, J. M., Boueilh, T., Simard,G., Boucret, L., Ferré-L’Hotellier, V., Tessier, L., Gadras, C., Bouet,P.E., Descamps, P., Procaccio, V., Reynier, P., May-Panloup, P. Targeted metabolomics reveals reduced levels of polyunsaturated choline plasmalogens and a smaller dimethyl-arginine/arginine ratio in the follicular fluid of patients with a diminished ovarian reserve. Hum Reprod 2017, 32(11), 2269-2278.
  • Stimpfel M, Hämäläinen RH, May-Panloup P. Mitochondria: More than Just "Power Plants" in Stem Cells. Stem Cells Int. 2017; 1826746. doi: 10.1155/2017/1826746. Epub 2017 Oct 12.
  • Taugourdeau A, Desquiret-Dumas V, Hamel JF, Chupin S, Boucret L, Ferré-L’Hotellier V, Bouet PE, Descamps P, Procaccio V, Reynier P, May-Panloup P. The mitochondrial DNA content of cumulus cells may help predict embryo implantation. J Assist Reprod Genet 2018 Oct 25.
  • May-Panloup P, Brochard V, Hamel JF, Desquiret-Dumas V, Chupin S, Reynier P, Duranthon V. Maternal ageing impairs mitochondrial DNA kinetics during early embryogenesis in mice. Hum Reprod. 2019 Jul 8;34(7):1313-1324.
  • Bouet PE, Chao de la Barca JM, El Hachem H, Descamps P, Legendre G, Reynier P, May-Panloup P.  Metabolomics shows no impairment of the microenvironment of the cumulus-oocyte complex in women with isolated endometriosis. Reprod Biomed Online. 2019 Dec;39(6):885-892.
  • Bouet PE, Chao de la Barca JM, Boucret L, Descamps P, Legendre G, Hachem HE, Blanchard S, Jeannin P, Reynier P, May-Panloup P. Elevated Levels of Monocyte Chemotactic Protein-1 in the Follicular Fluid Reveals Different Populations among Women with Severe Endometriosis. J Clin Med. 2020 May 1;9(5):1306.
  • Boucret L, Bouet PE, Riou J, Legendre G, Delbos L, Hachem HE, Descamps P, Reynier P, May-Panloup P. Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality. J Clin Med. 2020 Aug 1;9(8):E2478.
  • Boguenet M, Bocca C, Bouet P, Serri O, Chupin S, Tessier L, Blanchet O, El Hachem H, Chao de la Barca JM, Reynier P, May-Panloup P. Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia. Andrology 2020:andr.12882.
  • May-Panloup P, Boguenet M, El Hachem H, Bouet P-E, Reynier P. Embryo and Its Mitochondria. Antioxidants 2021;10:139.
  • Boguenet M, Bouet P-E, Spiers A, Reynier P, May-Panloup P. Mitochondria: their role in spermatozoa and in male infertility. Human Reproduction Update 2021:dmab001.
  • Boguenet M, Desquiret-Dumas V, Goudenège D, Bris C, Boucret L, Blanchet O, Procaccio V, Bouet P-E, Reynier P and May-Panloup P. Deep sequencing coupled with digital PCR shows that mitochondrial DNA content reduction in the most fertile spermatozoa is accompanied by increased mtDNA degradation. Human Reproduction (accepted).

 Collaborations

  • INRA Jouy en Josas UMR 1198.

 Acknowledgements for the financial supports

  • CHU Angers – Appel d’Offre Interne 2018.
  • Agence de la Biomédecine – Appel d’Offre Recherche “AMP, diagnostic prenatal et diagnostic génétique” 2020.
  • University Hospital of Angers, University of Angers, France, and the French national research centers INSERM and the CNRS.

Discover our teams

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