Batool Iqra, Kausar Rehana, Qamar Muhammad Shahbaz
Post Graduate Program of Veterinary Medicine, Federal University of Santa Maria (UFSM), Santa Maria, RS 97105-900, Brazil; Post Graduate Program of Animal Science, Laboratory of Animal Physiology, Federal university of Ceara (UFC), Brazil.
Animal Sciences Division, Nuclear Institute for Agriculture and Biology College, Pakistan Institute of Engineering and Applied Sciences (NIAB-C, PIEAS), Faisalabad, Pakistan.
Cytokine. 2025 Sep 19;196:157035. doi: 10.1016/j.cyto.2025.157035.
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.
低受孕率和早期胚胎丢失仍然是反刍动物繁殖效率的主要制约因素，尤其是在着床前期。母体对妊娠的识别（MRP）很大程度上由干扰素τ（IFNT）介导，IFNT是一种由伸长的孕体分泌的反刍动物特异性I型干扰素。最初，它因通过抑制子宫内膜前列腺素F2α（PGF2α）的抗黄体溶解作用而被认识。现在已知IFNT会在子宫之外产生全身效应。它能诱导子宫内膜和外周免疫细胞中的干扰素刺激基因，塑造有利于胚胎耐受的免疫环境。通过调节核因子κB、信号转导和转录激活因子1以及干扰素调节因子，IFNT下调促炎细胞因子，如肿瘤坏死因子α和干扰素γ，同时增强抗炎介质，包括白细胞介素-10和白细胞介素-4。这种转变促进了有利于母胎耐受的以辅助性T细胞2为主导的免疫特征。此外，IFNT通过减轻PGF2α诱导的黄体溶解并维持血管完整性来保护黄体功能。这是通过下调促退化基因，如转化生长因子β1、内皮素1、血小板反应蛋白1/2和丝氨酸蛋白酶家族E成员1，同时上调血管生成介质，如血小板衍生生长因子亚基B来实现的。这些作用稳定了黄体微环境并确保持续的孕酮分泌。本综述强调了IFNT在MRP中的关键作用，着重阐述了其在黄体维持、ISG诱导和免疫调节方面的内分泌和旁分泌作用。它还探讨了IFNT作为早期妊娠检测生物标志物的潜力及其在生殖生物技术中的应用，以牛的数据为支撑，并参考绵羊、小鼠和人类模型以获得转化见解。
