Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, USA.
Reproduction. 2024 Sep 4;168(4). doi: 10.1530/REP-24-0130. Print 2024 Oct 1.
The trophectoderm of the elongating conceptuses of cattle, sheep, and pigs secrete high amounts of interferons that increase or induce the expression of interferon-stimulated genes (ISGs) in the endometrium. Research concerning ISGs, performed from 1995 through 2023, is reviewed in this manuscript.
Expression of the classical interferon (IFN) stimulated genes (ISGs) increases in the endometrial stroma and glandular epithelium (GE) through activation of signal transducer and activator of transcription (STAT) signaling in response to the secretion of IFN tau (IFNT) and IFN gamma (IFNG) by the conceptuses of ruminants, including cattle and sheep, and pigs, respectively. The first of the classical ISGs to be characterized was ISG15 in cattle. Classical ISGs are not expressed by the endometrial luminal epithelium (LE) due to the expression of interferon regulatory factor 2 (IRF2) in the LE that prevents the expression of ISGs in the LE. Classical ISG expression in the endometrium serves as a reliable indicator of conceptus health and elongation in cattle. There are also nonclassical ISGs that are upregulated in endometrial LE in response to progesterone (P4) that are further stimulated by IFNT in sheep, the intracellular signaling pathway responsible for IFN effects on expression is unknown. ISGs are also upregulated in extrauterine tissues including CL and peripheral blood mononuclear cells (PBMCs). The expression of ISGs by the PBMCs of cattle serves as an early prognosticator of pregnancy. The physiological roles of ISGs remain obscure, but evidence suggests that they are at least in part involved in modifying the immune system to support endometrial remodeling necessary for the successful implantation of the conceptus. Our understanding of these ISGs is primarily the result of work from the laboratories of Drs Fuller Bazer, Thomas (Tod) Hansen, Gregory Johnson, Hakhyun Ka, Patrick Lonergan, Troy Ott, and Thomas Spencer.
牛、绵羊和猪的延长胚泡的滋养层大量分泌干扰素，增加或诱导子宫内膜中干扰素刺激基因（ISGs）的表达。本文综述了 1995 年至 2023 年期间关于 ISGs 的研究。
通过信号转导和转录激活因子（STAT）信号的激活，反刍动物（包括牛和绵羊以及猪）的胚泡分泌 IFNtau（IFNT）和 IFNgamma（IFNG），导致子宫内膜基质和腺上皮（GE）中经典干扰素（IFN）刺激基因（ISGs）的表达增加。首先在牛中鉴定的经典 ISG 是 ISG15。由于 LE 中干扰素调节因子 2（IRF2）的表达，阻止了 LE 中 ISG 的表达，因此 LE 中不表达经典 ISGs。经典 ISG 在牛子宫内膜中的表达是胚胎健康和延长的可靠指标。还有非经典的 ISGs，它们在子宫内膜 LE 中响应孕激素（P4）而上调，并在绵羊中进一步被 IFNT 刺激，负责 IFN 对表达影响的细胞内信号通路尚不清楚。ISGs 也在上皮外组织（包括 CL 和外周血单核细胞（PBMCs））中上调。牛 PBMCs 中 ISGs 的表达是妊娠的早期预测因子。ISGs 的生理作用仍然不清楚，但有证据表明，它们至少部分参与调节免疫系统，以支持成功植入胚胎所需的子宫内膜重塑。我们对这些 ISGs 的理解主要是由于 Fuller Bazer、Thomas（Tod）Hansen、Gregory Johnson、Hakhyun Ka、Patrick Lonergan、Troy Ott 和 Thomas Spencer 博士的实验室的工作。
