Estrous cycle stage-dependent manner of type I interferon-stimulated genes induction in the bovine endometrium

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  • SHIROZU Takahiro
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • IWANO Hiroki
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • OGISO Takatoshi
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • SUZUKI Toshiyuki
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • BALBOULA Ahmed Z.
    Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt
  • BAI Hanako
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • KAWAHARA Manabu
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan
  • KIMURA Koji
    Laboratory of Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, Japan
  • TAKAHASHI Hitomi
    Animal Breeding and Reproduction Research Division, NARO Institute of Livestock and Grassland Science, Ibaraki 305-8517, Japan
  • RULAN Bai
    Laboratory of Animal Breeding, Veterinary Medical Sciences, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo 113-8657, Japan
  • KIM Sung-Woo
    National Institute of Animal Science, Animal Genetic Resources Research Center, Namwon 590-832, Republic of Korea
  • YANAGAWA Yojiro
    Laboratory of Theriogenology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido 060-8589, Japan
  • NAGANO Masashi
    Laboratory of Theriogenology, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido 060-8589, Japan
  • IMAKAWA Kazuhiko
    Laboratory of Animal Breeding, Veterinary Medical Sciences, Graduate School of Agricultural and Life Science, The University of Tokyo, Tokyo 113-8657, Japan
  • TAKAHASHI Masashi
    Laboratory of Animal Genetics and Reproduction, Department of Animal Science, Research Faculty of Agriculture, Hokkaido University, Hokkaido 060-8589, Japan

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<p> Interferon tau (IFN-τ) is a ruminant-specific type I IFN secreted by a conceptus before its attachment to the uterus. IFN-τ induces the expression of IFN-stimulated genes (ISGs) via the type I IFN receptor (IFNAR), which is composed of IFNAR1 and IFNAR2 subunits in the endometrium. However, expression patterns of IFNARs during the estrous cycle have not been reported. We hypothesized that the response to a type I IFN changes along with IFNARs and the IFN-regulatory factors (IRFs) driving transcription of IFN signal-related genes and modulating a type I IFN signal during the estrous cycle. We investigated the estrous cycle stage-dependent type I IFN induction of ISGs and expression patterns of IFN signal-related genes in bovine endometrial tissues. Endometrial tissue pieces collected from bovine uteri at each estrous stage (early, mid, and late) were cultured with or without recombinant bovine IFN-α or concentrated pregnant uterine flushing (PUF) on day 18 after confirming the presence of a conceptus. IFN-α and PUF each significantly increased the expression of ISGs in endometrial tissues. The induction levels of the typical ISGs (MX1-a and ISG15) were significantly higher at the mid stage and correlated with high expression of IRFs at the mid stage. The immunostaining of IFNARs showed strong fluorescence intensities in luminal and glandular epithelia at the early and mid stages. Collectively, these results suggest that the endometrium exhibits estrous cycle stage-dependent responsiveness to type I IFN that may be associated with the expression of IFNARs and IRFs for pregnancy recognition.</p>

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