Dialogue(s) for fertility: deciphering spermatozoa-oviduct interactions and their implications for artificial insemination in dairy cattle

• Applicant: Professorin Dr. Jennifer Schön
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry ; Animal Physiology and Biochemistry ; Reproductive Medicine, Urology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 406942793

• Final Report Year: 2024

Final Report Abstract

The oviducts (or Fallopian tubes in humans) are central reproductive organs in which the final maturation of germ cells, fertilization and early embryonic development take place. Before fertilization, male gametes bind to the epithelial cells lining the lumen of the proximal part of the oviduct, the isthmus. The epithelial cells build a “reservoir” where the gametes mature, are selected, stored and released in order to provide an optimal number of fertile sperm at the time of ovulation. The molecular mechanisms of oviductal sperm storage and release in cattle are largely unknown. Therefore, the German-French DIALOG project aimed at 1) characterizing the oviductal fluid proteome in spatio-temporal resolution; 2) establishing cell culture models for mechanistic studies in the reservoir; 3) characterizing sperm-epithelium and sperm-fluid interactions; 4) deciphering the mechanisms of sperm-oviduct interactions. The oviductal fluid analysis conducted by the French project partner resulted in the most comprehensive mammalian oviductal fluid proteome published so far and revealed that oviduct region, proximity to the ovulation site and cycle stage largely influence the protein composition of the fluid. Furthermore, sperm-interacting proteins within the oviductal fluid were identified. The DIALOG cooperation partners created compartmentalised air-liquid interface and 3D spheroid models of different regions of the oviduct, which enabled the simulation of oestrus cycle stages and sperm binding studies in vitro. The project partners further developed a protocol for the proteome analysis of samples obtained by laser microdissection from fixed, paraffin-embedded oviduct epithelial tissue. This approach was used to identify new candidate proteins potentially involved in the binding of sperm to the reservoir. The results indicate a coordinated interplay between sperm-interacting proteins in the oviductal fluid and on the epithelial cells. In conclusion, the DIALOG project has provided new insights into the complex, dynamic composition of the bovine sperm reservoir. The models and methods established during the funding period lay the foundation for future comparative studies of the sperm reservoir in species with divergent reproductive strategies, which will serve to improve fertility in domestic animals and support conservation efforts in wildlife species.

Link to the final report

https://doi.org/10.4126/FRL01-006511250

Publications

• Air‐liquid interface cell culture: From airway epithelium to the female reproductive tract. Reproduction in Domestic Animals, 54(S3), 38-45.
  Chen, Shuai & Schoen, Jennifer
  
• Composing the Early Embryonic Microenvironment: Physiology and Regulation of Oviductal Secretions. International Journal of Molecular Sciences, 21(1), 223.
  Saint-Dizier, Marie; Schoen, Jennifer; Chen, Shuai; Banliat, Charles & Mermillod, Pascal
  
• Sperm interactions with the female reproductive tract: A key for successful fertilization in mammals. Molecular and Cellular Endocrinology, 516, 110956.
  Saint-Dizier, Marie; Mahé, Coline; Reynaud, Karine; Tsikis, Guillaume; Mermillod, Pascal & Druart, Xavier
  
• Sperm migration, selection, survival, and fertilizing ability in the mammalian oviduct. Biology of Reproduction, 105(2), 317-331.
  Mahé, Coline; Zlotkowska, Aleksandra Maria; Reynaud, Karine; Tsikis, Guillaume; Mermillod, Pascal; Druart, Xavier; Schoen, Jennifer & Saint-Dizier, Marie
  
• Using the Air–Liquid Interface Approach to Foster Apical–Basal Polarization of Mammalian Female Reproductive Tract Epithelia In Vitro. Methods in Molecular Biology, 251-262. Springer US.
  Chen, Shuai & Schoen, Jennifer
  
• Air-liquid interface models of the oviduct epithelium: advances, applications, and challenges. ICAR, Bologna, Italy.
  Schoen, J. & Chen, S.
  
• Role of secreted proteins and heparan sulfate on sperm binding to oviduct epithelial cells in cattle. AETE, Utrecht, Netherlands.
  Mahé, C.
  
• Spatiotemporal profiling of the bovine oviduct fluid proteome around the time of ovulation. Scientific Reports, 12(1).
  Mahé, Coline; Lavigne, Régis; Com, Emmanuelle; Pineau, Charles; Locatelli, Yann; Zlotkowska, Aleksandra Maria; Almiñana, Carmen; Tsikis, Guillaume; Mermillod, Pascal; Schoen, Jennifer & Saint-Dizier, Marie
  
• Spatiotemporal regulation of sperm-interacting proteins in the bovine oviduct fluid around the time of ovulation. ICAR, Bologna, Italy
  Mahé, C.
  
• The proteomic landscape of the oviduct fluid around the time of fertilization in cattle. ICAR, Bologna, Italy
  Mahé, C.
  
• Modelling the oviduct epithelium in vitro: oxygen level and media regime influence functional parameters of oviduct epithelial cells cultured at the air-liquid interface. DVR congress, Bonn, Germany.
  Huo, J.
  
• Sperm-fluid-cell interplays in the bovine oviduct: glycosaminoglycans modulate sperm binding to the isthmic reservoir. Scientific Reports, 13(1).
  Mahé, Coline; Pranomphon, Thanya; Reynaud, Karine; Laffont, Ludivine; Meylheuc, Thierry; Schoen, Jennifer; Mermillod, Pascal & Saint-Dizier, Marie
  
• The sperm-interacting proteome in the bovine isthmus and ampulla during the periovulatory period. Journal of Animal Science and Biotechnology, 14(1).
  Mahé, Coline; Lavigne, Régis; Com, Emmanuelle; Pineau, Charles; Zlotkowska, Aleksandra Maria; Tsikis, Guillaume; Mermillod, Pascal; Schoen, Jennifer & Saint-Dizier, Marie
  
• Oxygen levels affect oviduct epithelium functions in air–liquid interface culture. Histochemistry and Cell Biology, 161(6), 521-537.
  Huo, Jianchao; Mówińska, Aleksandra Maria; Eren, Ali Necmi; Schoen, Jennifer & Chen, Shuai