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Oviduct as a sensor of embryo quality: deciphering the extracellular vesicle (EV)-mediated embryo-maternal dialogue


Embryo-derived extracellular vesicles (EVs) may play a role in mediating the embryo-maternal dialogue at the oviduct, potentially carrying signals reflecting embryo quality. We investigated the effects of bovine embryo-derived EVs on the gene expression of bovine oviductal epithelial cells (BOECs), and whether these effects are dependent on embryo quality. Presumptive zygotes were cultured individually in vitro in culture medium droplets until day 8 while their development was assessed at day 2, 5 and 8. Conditioned medium samples were collected at day 5 and pooled based on embryo development (good quality embryo media and degenerating embryo media). EVs were isolated from conditioned media by size exclusion chromatography and supplemented to primary BOEC monolayer cultures to evaluate the effects of embryo-derived EVs on gene expression profile of BOEC. Gene expression was quantified by RNA-seq and RT-qPCR. A total of 7 upregulated and 18 downregulated genes were detected in the BOECs supplemented with good quality embryo-derived EV compared to the control. The upregulated genes included interferon-τ-induced genes, such as OAS1Y, MX1 and ISG15, which have previously been reported as upregulated in the oviductal epithelial cells in the presence of embryos. Of the upregulated genes, OAS1Y and MX1 were validated with RT-qPCR. In contrast, only one differentially expressed gene was detected in BOECs in response to degenerating embryo-derived EVs, suggesting that oviductal responses are dependent on embryo quality. Our results support the hypothesis that embryo-derived EVs are involved in embryo-maternal communication at the oviduct and the oviductal response is dependant on the embryo quality.

Key messages

• Extracellular vesicles (EVs) released by individually cultured pre-implantation bovine embryos can alter the gene expression of primary oviductal epithelial cells.

• The oviductal response, in terms of gene expression, to the bovine embryo-derived EVs varied depending on the embryo quality.

• In vivo, the oviduct may have the ability to sense the quality of the pre-implantation embryos.

• The observed effect of embryo-derived EVs on oviductal epithelial cells could serve as a non-invasive method of evaluating the embryo quality.

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Data availability

The RNA sequencing data has been uploaded to the NCBI SRA repository ( under NCBI BioProject ID PRJNA660346.


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We thank Annika Häling for her support during the laboratory work.


This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 668989 (TRANSGENO) and 857418 (COMBIVET); the Estonian Ministry of Education and Research (grant IUT34-16); Enterprise Estonia (grant EU48695); the European Commission Horizon 2020 research and innovation programme under grant agreement 692065 (Project WIDENLIFE) and European Commission Horizon 2020 research and innovation programme under grant agreement 692299 (Project SEARMET); Rep-Eat-H2020-MSCA-COFUND 713714.

Author information




KD, AF and MN developed the concept and designed the experiments; MN and YR produced embryos in vitro; QR carried out primary BOEC culture; KD carried out EV isolation, extended BOEC culture, EV supplementation and RNA extraction; KJ and AVM carried out RNAseq library preparation and RNAseq; JV did BOEC immunofluorescence assay; FL and JO carried out RNAseq data analysis; KD and KG carried out RT-qPCR; KD wrote the manuscript with conceptual contribution from JO, FL and AF; AF, ÜJ and AS supervised KD. All authors approved the final manuscript.

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Correspondence to Alireza Fazeli.

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Supplementary information

Online Resource 1

, file format-.pdf, Primer sequences of the genes used for qPCR (PDF 194 kb)

Online Resource 2

, file format-.xls, Good embryo-derived EVs supplemented BOECs vs Control BOECs, RNAseq differential gene expression analysis (XLSX 966 kb)

Online Resource 3

, file format-.xls, Degenerating embryo-derived EVs supplemented BOECs vs Control BOECs, RNAseq differential gene expression analysis (XLSX 958 kb)

Online Resource 4

, file format-.xls, Good embryo-derived EVs supplemented BOECs vs degenerating embryo-derived EVs supplemented BOECs, RNAseq differential gene expression analysis (XLSX 959 kb)

Online Resource 5

, file format-.xls, Good_vs_control_kegg_gsea, GSEA with KEGG pathway annotations based on the results of differential expression tests (XLS 120 kb)

Online Resource 6

, file format-.xls, Good_vs_degenerating_kegg_gsea, GSEA with KEGG pathway annotations based on the results of differential expression tests (XLS 118 kb)

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Dissanayake, K., Nõmm, M., Lättekivi, F. et al. Oviduct as a sensor of embryo quality: deciphering the extracellular vesicle (EV)-mediated embryo-maternal dialogue. J Mol Med 99, 685–697 (2021).

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  • Bovine embryo
  • Embryo-maternal communication
  • Extracellular vesicles
  • Oviduct