Concentration-dependent type 1 interferon-induced regulation of mx1 and fabp3 in bovine endometrial explants

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Abstract

The inadequate maternal recognition of embryonic interferon τ (IFNτ) might explain subfertility in cattle. This study aimed at modeling the inducibility of type 1 interferon receptor subunits 1/2 (IFNAR1/2), mimicking competition between IFNτ and infection-associated interferon α (IFNα), and simulating type 1 interferon pathways in vitro. Endometrial explants (n = 728 from n = 26 healthy uteri) were collected at the abattoir, challenged with IFNτ and/or IFNα in different concentrations, and incubated for 24 h. Gene expression analysis confirmed the inducibility of IFNAR1/2 within this model, it being most prominent in IFNAR2 with 10 ng/mL IFNα (p = 0.001). The upregulation of interferon-induced GTP-binding protein (MX1, classical pathway) was higher in explants treated with 300 ng/mL compared to 10 ng/mL IFNτ (p < 0.0001), whereas the non-classical candidate fatty acid binding protein 3 (FABP3) exhibited significant downregulation comparing 300 ng/mL to 10 ng/mL IFNτ. The comparison of explants challenged with IFNτ + IFNα indicated the competition of IFNτ and IFNα downstream of the regulatory factors. In conclusion, using this well-defined explant model, interactions between infection-associated signals and IFNτ were indicated. This model can be applied to verify these findings and to mimic and explore the embryo– maternal contact zone in more detail.

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Schabmeyer, S. T., Kneidl, A. M., Schneider, J. K., Kirsch, S., Zablotski, Y., Petzl, W., … Meyerholz, M. M. (2021). Concentration-dependent type 1 interferon-induced regulation of mx1 and fabp3 in bovine endometrial explants. Animals, 11(2), 1–14. https://doi.org/10.3390/ani11020262

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