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Concentration-Dependent Type 1 Interferon-Induced Regulation of MX1 and FABP3 in Bovine Endometrial Explants
Simone Tamara Schabmeyer1, Anna Maria Kneidl1, Julia Katharina Schneider1
1Clinic for Ruminants with Ambulatory and Herd Health Services, Centre for Clinical Veterinary Medicine Ludwig Maximilians University Munich, 85764 Oberschleissheim, Germany.
Insights
Maternal recognition of embryonic interferon tau (IFNτ) is key for cattle fertility. This study modeled how IFNτ and IFNα interact, revealing competition in type 1 interferon pathways and offering insights into subfertility causes.
Area of Science:
- Reproductive biology
- Immunology
- Molecular endocrinology
Background:
- Subfertility in cattle is linked to inadequate maternal recognition of embryonic interferon tau (IFNτ).
- Understanding type 1 interferon (IFN) pathways is crucial for reproductive success.
Purpose of the Study:
- To model the inducibility of type 1 interferon receptor subunits 1/2 (IFNAR1/2).
- To mimic competition between embryonic IFNτ and infection-associated IFNα.
- To simulate type 1 interferon signaling pathways in vitro.
Main Methods:
- Endometrial explants from healthy cattle uteri were challenged with varying concentrations of IFNτ and/or IFNα.
- Incubation for 24 hours followed by gene expression analysis.
- Investigated inducibility of IFNAR1/2, MX1 (classical), and FABP3 (non-classical) pathways.
Main Results:
- IFNAR1/2 inducibility was confirmed, with IFNAR2 most responsive to 10 ng/mL IFNα.
- Upregulation of MX1 was dose-dependent on IFNτ, while FABP3 showed significant downregulation.
- IFNτ and IFNα competed downstream of regulatory factors in explants treated with both.
Conclusions:
- A well-defined in vitro explant model demonstrated interactions between infection-associated signals and embryonic IFNτ.
- This model can explore embryo-maternal communication and verify findings on bovine subfertility.
- Competition within type 1 interferon pathways may contribute to reproductive challenges in cattle.
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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