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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)

 

 

pascale.may-panloup @ 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. 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;

  • We have disclosed a link between the mitochondrial genetics i.e. the mitochondrial haplogroups and ovarian reserve depletion, with the JT macro-haplogroup playing a protective role in ovarian aging (2014).
  • 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).
  • Finally, using a murine model, we demonstrated a dysregulation of mtDNA kinetics in early embryogenesis during ageing (manuscript in revision)

  People involved

  • Seniors: Pascal Reynier, Pascale May-Panloup
  • Students: Lisa Boucret, Arthur Clément, Alexis Taugourdeau, Magalie Boguenet
  • Engineers/technicians : Valérie Desquiret-Dumas, Stéphanie Chupin

 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 201732(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.
  • 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.
  • 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.

 Collaborations:

  • INRA Jouy en Josas UMR 1198

 Acknowledgements for the financial supports

  • Agence de la Biomédecine – Appel d’Offre Recherche “AMP, diagnostic prenatal et diagnostic génétique” 2017
  • University Hospital of Angers, University of Angers, France, and the French national research centers INSERM and the CNRS.
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