Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Olson Center for Women's Health, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE 68198-3255, USA.
Biol Reprod. 2024 Sep 14;111(3):667-677. doi: 10.1093/biolre/ioae084.
Conceptus-derived interferon-tau (IFNT) initiates maternal recognition of pregnancy in ewes by paracrine actions on the endometrium and endocrine action on the corpus luteum (CL). To examine the effect of IFNT on the CL without inducing IFN-stimulated genes (ISGs) in the endometrium, recombinant ovine IFNT (roIFNT) or bovine serum albumin was delivered directly into CLs via osmotic pumps at a rate of 10, 50, or 100 ng/h from days 9 to 12 of the estrous cycle. Endometrial and CL samples were collected on day 12. 50 ng/h of roIFNT induced ISG15 in the CL on day 12 without affecting endometrial ISG15 concentrations. In a second experiment, roIFNT (50 ng/h) was infused into the CL from days 10 to 17 of the estrous cycle and serum samples were collected daily. Serum progesterone concentrations were significantly higher from days 15 to 17 in roIFNT-infused ewes compared to controls. Levels of LHCGR, STAR, CYP11A1, HSL, OPA1, and protein kinase A mRNA and proteins were higher in the roIFNT-infused CLs compared to the controls. Levels of ISG15 and MX1 mRNA increased in the CLs of roIFNT-infused ewes but not in the endometrium. Endometrial ESR1 mRNA and protein concentrations were higher in the controls compared to roIFNT-infused ewes. In conclusion, intra-luteal delivery of roIFNT induced ISGs, stabilized steroidogenesis in the CL, and delayed luteolysis without inducing endometrial IFN-stimulated genes. Inhibition of ESR1 in the endometrium of roIFNT-infused ewes was observed suggesting that direct delivery of IFNT to the CL has an additional anti-luteolytic effect on the endometrium.
概念滋养层衍生的干扰素-τ（IFNT）通过旁分泌作用于子宫内膜和内分泌作用于黄体（CL）来启动母羊对妊娠的识别。为了在不诱导子宫内膜中 IFN 刺激基因（ISGs）的情况下研究 IFNT 对 CL 的影响，通过渗透泵以每天 10、50 或 100ng/h 的速率从发情周期的第 9 天到第 12 天将重组绵羊 IFNT（roIFNT）或牛血清白蛋白直接递送至 CL。在第 12 天采集子宫内膜和 CL 样本。每天 50ng/h 的 roIFNT 在第 12 天诱导 CL 中的 ISG15，而不影响子宫内膜 ISG15 浓度。在第二个实验中，roIFNT（50ng/h）从发情周期的第 10 天到第 17 天被输注到 CL 中，并且每天采集血清样本。与对照组相比，roIFNT 输注母羊的血清孕激素浓度从第 15 天到第 17 天显著升高。roIFNT 输注 CL 中的 LHCGR、STAR、CYP11A1、HSL、OPA1 和蛋白激酶 A mRNA 和蛋白水平高于对照组。roIFNT 输注母羊的 CL 中的 ISG15 和 MX1 mRNA 水平增加，但子宫内膜中没有增加。与 roIFNT 输注母羊相比，对照组的子宫内膜 ESR1 mRNA 和蛋白浓度更高。总之，roIFNT 的黄体内递送诱导了 ISGs，稳定了 CL 中的类固醇生成，并延迟了黄体溶解，而没有诱导子宫内膜中的 IFN 刺激基因。在 roIFNT 输注母羊的子宫内膜中观察到 ESR1 抑制，表明 IFNT 直接递送至 CL 对子宫内膜具有额外的抗黄体溶解作用。
