Diao Honglu, Xiao Shuo, Zhou Tong, Martin Taylor E, Watford Wendy T, Ye Xiaoqin
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA.
Reprod Dev Med. 2024 Mar;8(1):61-65. doi: 10.1097/RD9.0000000000000090. Epub 2024 Jan 15.
The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological mother) or an allogeneic embryo (to a surrogate) for implantation. To gain insights, we examined uterine early response genes approaching embryo attachment on day 3 post coitum (D3) at 22 hours when blue dye reaction, an indication of embryo attachment, had not manifested in mice. C57BL/6 pseudo-pregnant (control) and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis. The self-assembling-manifold () algorithm identified 21,858 unique probesets. Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups. There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change (fc) >1.5 and value <5%. Gene ontology (GO) analysis of the 106 upregulated genes revealed 38 significant GO biological process (GOBP) terms ( <0.05), and 32 (84%) of them were associated with immune responses, with a dominant natural killer (NK) cell activation signature. Among the top eight upregulated protein-coding genes, inactivates retinoic acid (RA) while promotes vitamin A storage, both of which are expected to attenuate RA bioavailability; and play roles in ion transport and transmembrane transport; , , and are involved in immune responses; and is important for kynurenine pathway. Most of these genes or their related pathways have functions in immune regulations. RA signaling has been implicated in immune tolerance and immune homeostasis, and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta. The mechanisms of immune responses approaching embryo attachment remain to be elucidated. The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.
子宫对胚胎着床具有短暂的接受性。子宫为何不排斥半同种异体胚胎（相对于生物学母亲而言）或同种异体胚胎（相对于代孕母亲而言）以供着床，这一点仍有待了解。为了深入探究，我们在交配后第3天（D3）的22小时检查了接近胚胎附着时子宫的早期反应基因，此时在小鼠中尚未出现作为胚胎附着指标的蓝色染料反应。在D3的22小时收集C57BL/6假孕（对照）和怀孕小鼠的子宫用于微阵列分析。自组装流形（）算法识别出21,858个独特的探针集。主成分分析表明假孕组和怀孕组之间有明显区分。怀孕子宫中有106个上调和5个下调的蛋白质编码基因，其倍数变化（fc）>1.5且 值<5%。对这106个上调基因的基因本体（GO）分析揭示了38个显著的GO生物学过程（GOBP）术语（<0.05），其中32个（84%）与免疫反应相关，具有占主导地位的自然杀伤（NK）细胞激活特征。在上调程度最高的前八个蛋白质编码基因中，抑制视黄酸（RA），而促进维生素A储存，这两者都预期会减弱RA的生物利用度；和在离子转运和跨膜运输中起作用；、和参与免疫反应；并且对犬尿氨酸途径很重要。这些基因中的大多数或其相关途径在免疫调节中发挥作用。RA信号传导与免疫耐受和免疫稳态有关，子宫NK细胞与胎盘母婴界面的免疫耐受有关。接近胚胎附着时免疫反应的机制仍有待阐明。早期反应基因的协同作用可能是子宫不排斥着床胚胎这一问题的关键所在。
