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Peer-reviewedCC BY 4.0Nature Communications

Pregnancy establishment in cattle without embryonic interferon tau

  • Asghar Ali1,2
  • Valeri Zakhartchenko3,4
  • Tuna Güngör3,4
  • Stefan Nüske5
  • Jan B. Stöckl6
  • Sarah Hecken6
  • Andreas Hauser6
  • Stefan Krebs6
  • Sven Reese7
  • Marcel Suchowski8
  • Robert Friedl9
  • Sebastian Schwanitz5
7 more authors
  • Armin Manfred Scholz5
  • Andreas Blutke10
  • Martina Protschka11
  • Mathias Büttner11
  • Thomas Fröhlich6
  • Horst-Dieter Reichenbach12
  • Eckhard Wolf13,14,15
15 affiliations
  1. 1Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany. [email protected]
  2. 2Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany. [email protected]
  3. 3Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany
  4. 4Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany
  5. 5Livestock Center, Faculty of Veterinary Medicine, LMU Munich, Oberschleißheim, Germany
  6. 6Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany
  7. 7Department of Veterinary Sciences, Chair of Anatomy, Histology and Embryology, LMU Munich, Munich, Germany
  8. 8Bavarian Health and Food Safety Authority (LGL), Oberschleißheim, Germany
  9. 9Vion Waldkraiburg GmbH, Waldkraiburg, Germany
  10. 10Institute of Veterinary Pathology, Center for Clinical Veterinary Medicine, LMU Munich, Munich, Germany
  11. 11Institute of Immunology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
  12. 12Institute for Animal Breeding, Bavarian State Research Center for Agriculture (LfL), Grub, Germany
  13. 13Center for Innovative Medical Models (CiMM), LMU Munich, Oberschleißheim, Germany. [email protected]
  14. 14Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany. [email protected]
  15. 15Laboratory for Functional Genome Analysis (LAFUGA), Gene Center, LMU Munich, Munich, Germany. [email protected]
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Abstract

In ruminants, embryonic interferon tau (IFNT) is widely considered the indispensable signal for maternal recognition of pregnancy, driving endometrial gene expression to prevent luteolysis. However, this canonical paradigm has never been directly tested using genomic loss-of-function models. Here we show that IFNT is completely dispensable for pregnancy recognition, luteal maintenance, and full-term gestation in cattle. Using CRISPR-Cas9, we generate bovine fibroblasts lacking all functional copies of the multigene IFNT locus for somatic cell nuclear transfer. IFNT -null embryos develop into blastocysts in vitro at normal rates and exhibit typical elongation at day 18 post-transfer without inducing endometrial interferon-stimulated genes. Crucially, these IFNT -null conceptuses successfully prevent luteal regression, establish normal placentation, and progress through full-term gestations, culminating in the birth of healthy female calves. These findings provide the first direct genetic evidence that embryonic IFNT is dispensable for pregnancy recognition and establishment in cattle, fundamentally revising the long-standing model of ruminant reproduction and uncovering alternative embryo-maternal signaling mechanisms.

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Cite

BibTeXRIS
BibTeX
@article{ali2026pregnancy,
  title = {{Pregnancy establishment in cattle without embryonic interferon tau}},
  author = {Asghar Ali and Valeri Zakhartchenko and Tuna Güngör and Stefan Nüske and Jan B. Stöckl and Sarah Hecken and Andreas Hauser and Stefan Krebs and Sven Reese and Marcel Suchowski and Robert Friedl and Sebastian Schwanitz and Armin Manfred Scholz and Andreas Blutke and Martina Protschka and Mathias Büttner and Thomas Fröhlich and Horst-Dieter Reichenbach and Eckhard Wolf},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78446-4},
  url = {https://www.nature.com/articles/s41467-026-78446-4},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Pregnancy establishment in cattle without embryonic interferon tau
AU  - Asghar Ali
AU  - Valeri Zakhartchenko
AU  - Tuna Güngör
AU  - Stefan Nüske
AU  - Jan B. Stöckl
AU  - Sarah Hecken
AU  - Andreas Hauser
AU  - Stefan Krebs
AU  - Sven Reese
AU  - Marcel Suchowski
AU  - Robert Friedl
AU  - Sebastian Schwanitz
AU  - Armin Manfred Scholz
AU  - Andreas Blutke
AU  - Martina Protschka
AU  - Mathias Büttner
AU  - Thomas Fröhlich
AU  - Horst-Dieter Reichenbach
AU  - Eckhard Wolf
PY  - 2026
DA  - 2026/10/08
JO  - Nature Communications
DO  - 10.1038/s41467-026-78446-4
UR  - https://www.nature.com/articles/s41467-026-78446-4
AB  - In ruminants, embryonic interferon tau (IFNT) is widely considered the indispensable signal for maternal recognition of pregnancy, driving endometrial gene expression to prevent luteolysis. However, this canonical paradigm has never been directly tested using genomic loss-of-function models. Here we show that IFNT is completely dispensable for pregnancy recognition, luteal maintenance, and full-term gestation in cattle. Using CRISPR-Cas9, we generate bovine fibroblasts lacking all functional copies of the multigene IFNT locus for somatic cell nuclear transfer. IFNT -null embryos develop into blastocysts in vitro at normal rates and exhibit typical elongation at day 18 post-transfer without inducing endometrial interferon-stimulated genes. Crucially, these IFNT -null conceptuses successfully prevent luteal regression, establish normal placentation, and progress through full-term gestations, culminating in the birth of healthy female calves. These findings provide the first direct genetic evidence that embryonic IFNT is dispensable for pregnancy recognition and establishment in cattle, fundamentally revising the long-standing model of ruminant reproduction and uncovering alternative embryo-maternal signaling mechanisms.
SN  - 2041-1723
ER  -