Author(s)

  • Océane Girard (Presenting Author) | Nantes University, CHU Nantes, Inserm, CR2TI | 30, Boulevard Jean Monnet, 44093, Nantes, France
  • Régis Lavigne | Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Biosit – UMS 3480, US_S 018 | 9 Avenue du Professeur Léon Bernard, 35000, Rennes, France
  • Samuel Besseau | Nantes University, CHU Nantes, Inserm, CR2TI | 30, Boulevard Jean Monnet, 44093, Nantes, France
  • Eva Moinard | Nantes University, CHU Nantes, Inserm, CR2TI | 30, Boulevard Jean Monnet, 44093, Nantes, France
  • Maelys Le Gallou | Nantes University, CHU Nantes, Inserm, CR2TI | 30, Boulevard Jean Monnet, 44093, Nantes, France
  • Jenna Lammers | CHU Nantes, Service de Biologie de la Reproduction | 38, Boulevard Jean Monnet, 44093, Nantes, France
  • Maena Le Corvec | Univ Rennes, UAR 2025 ScanMAT | Campus de Beaulieu, 35000, Rennes, France
  • Emmanuelle Com | Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Biosit – UMS 3480, US_S 018 | 9 Avenue du Professeur Léon Bernard, 35000, Rennes, France
  • Alain Moreac | Univ Rennes, IPR (Institut de Physiques de Rennes) - CNRS-UMR 6251 | Campus de Beaulieu, 35000, Rennes, France
  • Charles Pineau | Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Biosit – UMS 3480, US_S 018 | 9 Avenue du Professeur Léon Bernard, 35000, Rennes, France
  • Arnaud Reignier | CHU Nantes, Service de Biologie de la Reproduction | 38, Boulevard Jean Monnet, 44093, Nantes, France
  • Thomas Freour | CHU Nantes, Service de Biologie de la Reproduction | 38, Boulevard Jean Monnet, 44093, Nantes, France
  • Laurent David | Nantes University, CHU Nantes, Inserm, CR2TI | 30, Boulevard Jean Monnet, 44093, Nantes, France

Abstract

Infertility concerns 1 out 6 couples wishing to conceive and the worldwide use of assisted reproduction technique increases by 5 to 10% each year. Nevertheless, the average success rate for in vitro fertilization (IVF), is only around 27%. Understanding the window of human embryo peri-implantation development (hEPID) is essential to appreciate the beginning of human life but also for multiple clinical approaches such as IVF and placenta physiopathology.

Here, we investigated the proteome of human embryo by MS at 4 days post fertilization (dpf), 6dpf, and after prolonged culture, equivalent to post-implantation, at 8dpf and 10dpf. Our DIA approach identified 3,846 to 4,716 proteins. By combining proteome analysis with scRNAseq and metabolome analysis, we highlighted gene regulatory networks, metabolic capacities and implantation strategies established upon implantation. In particular, we identified GCM1 and GRHL1 transcription factors as specific markers of polar trophectoderm, the cells of the embryo that are adhering to the endometrium. We also identified integrin α5:β1–fibronectin as the main adhesion molecules present at the embryo-endometrium interface upon implantation. Finally, we mapped metabolic shifts required including glucose/pyruvate dynamics during hEPID.

Altogether, our work lead to the first proteome landscape of the hEPID. We are now following up to identify druggable targets to improve implantation of embryos in patients with recurrent implantation failure.