Cervico-vaginal ISGs and interferon tau: emerging biomarkers for early pregnancy detection in cattle

Early pregnancy detection in cattle is essential for improving reproductive efficiency, reducing days open, and enabling timely rebreeding of non-pregnant animals. Although several pregnancy diagnostic methods are available, none can reliably identify pregnancy before Day 21 post-insemination. Interferon tau (IFNT), the pregnancy recognition signal produced by the ruminant conceptus, initiates maternal responses through the induction of interferon-stimulated genes (ISGs). While this response is most pronounced in the endometrium, recent studies have shown that the cervix and vagina also respond to conceptus-derived IFNT, creating new possibilities for minimally invasive early pregnancy diagnosis. This review summarizes recent findings on the dynamics of ISG expression in the cervix and vagina, the detection of IFNT in cervico-vaginal secretions, and the diagnostic performance of these biomarkers. Available evidence indicates that cervical and vaginal tissues respond to conceptus-derived IFNT by upregulating the classical ISGs (ISG15, MX1, and MX2) as early as Days 14-16 post-insemination, coinciding with maternal recognition of pregnancy. Notably, cervical ISG15 expression on Day 16 demonstrates excellent diagnostic performance (AUC = 1.0). Furthermore, IFNT has been detected in cervical secretions on Days 16-19 with reported sensitivities of 94.5% in dairy cows and 96.6-100% in beef cows. The review also discusses the possible routes by which IFNT reaches the cervix and vagina and highlights the potential of IFNT-based lateral-flow assays for on-farm pregnancy diagnosis. Overall, the available evidence supports cervico-vaginal ISGs and IFNT as biologically grounded, minimally invasive biomarkers for the development of field-applicable early pregnancy diagnostic kits for dairy and beef cattle.