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Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos.

Ryan M Finnerty | Daniel J Carulli | Akshata Hedge | Yanli Wang | Frimpong Boadu | Sarayut Winuthayanon | Jianlin Jack Cheng | Wipawee Winuthayanon
eLife | 2025

The oviduct is the site of fertilization and preimplantation embryo development in mammals. Evidence suggests that gametes alter oviductal gene expression. To delineate the adaptive interactions between the oviduct and gamete/embryo, we performed a multi-omics characterization of oviductal tissues utilizing bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and proteomics collected from distal and proximal at various stages after mating in mice. We observed robust region-specific transcriptional signatures. Specifically, the presence of sperm induces genes involved in pro-inflammatory responses in the proximal region at 0.5 days post-coitus (dpc). Genes involved in inflammatory responses were produced specifically by secretory epithelial cells in the oviduct. At 1.5 and 2.5 dpc, genes involved in pyruvate and glycolysis were enriched in the proximal region, potentially providing metabolic support for developing embryos. Abundant proteins in the oviductal fluid were differentially observed between naturally fertilized and superovulated samples. RNA-seq data were used to identify transcription factors predicted to influence protein abundance in the proteomic data via a novel machine learning model based on transformers of integrating transcriptomics and proteomics data. The transformers identified influential transcription factors and correlated predictive protein expressions in alignment with the in vivo-derived data. Lastly, we found some differences between inflammatory responses in sperm-exposed mouse oviducts compared to hydrosalpinx Fallopian tubes from patients. In conclusion, our multi-omics characterization and subsequent in vivo confirmation of proteins/RNAs indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner.

Pubmed ID: 40009070

Associated grants

  • Agency: University of Missouri,
    Id: Start-up fund
  • Agency: National Science Foundation,
    Id: DBI2308699
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM008336
  • Agency: NIGMS NIH HHS, United States
    Id: T32GM008336
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD097087
  • Agency: National Science Foundation,
    Id: CCF2343612
  • Agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development,
    Id: R01HD097087
  • Agency: Washington State University,
    Id: RA+$10K

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