Interferon tau in ruminant reproduction: Mechanisms of maternal recognition of pregnancy and implications for fertility enhancement.

Low conception rates and early embryonic loss remain major constraints to reproductive efficiency in ruminants, particularly during the peri-implantation period. Maternal recognition of pregnancy (MRP) is largely mediated by interferon tau (IFNT), a ruminant-specific type I interferon secreted by the elongating conceptus. Initially recognized for its anti-luteolytic action through suppression of endometrial prostaglandin F2α, (PGF2α). IFNT is now known to exert systemic effects beyond the uterus. It induces interferon-stimulated genes in endometrial and peripheral immune cells, shaping an immune environment conducive to embryo tolerance. By modulating nuclear factor kappa B, signal transducer and activator of transcription 1, and interferon regulatory factors, IFNT downregulates pro-inflammatory cytokines such as tumor necrosis factor alpha and interferon gamma, while enhancing anti-inflammatory mediators including interleukin-10 and interleukin-4. This shift promotes a T-helper 2-dominant immune profile favorable for maternal-fetal tolerance. In addition, IFNT safeguards corpus luteum function by mitigating PGF2α-induced luteolysis and preserving vascular integrity. This occurs through downregulation of pro-regression genes such as transforming growth factor beta 1, endothelin 1, thrombospondin 1/2, and serpin family E member 1, alongside upregulation of angiogenic mediators such as platelet-derived growth factor subunit B. These actions stabilize the luteal microenvironment and ensure sustained progesterone secretion. This review highlights IFNT's pivotal role in MRP, emphasizing its endocrine and paracrine actions on luteal maintenance, ISG induction, and immune modulation. It also explores IFNT's potential as a biomarker for early pregnancy detection and its applications in reproductive biotechnology, with bovine data supported by ovine, murine, and human models for translational insights.