Center of Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Department of Andrology/Sichuan Human Sperm Bank, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Int J Med Sci. 2024 Oct 28;21(14):2824-2836. doi: 10.7150/ijms.101865. eCollection 2024.
In the early stages of pregnancy, the maternal-fetal interface is enriched with natural killer (NK) cells that release growth factors to support fetal development and promote the remodeling of uterine spiral arteries. Previous studies have shown that the aberrant frequency and activity of decidual natural killer (dNK) cells are associated with recurrent pregnancy loss (RPL). Various factors regulate the roles of dNK cells and their interactions with trophoblasts to facilitate the colonization and maturation of semiallogeneic embryos. However, knowing precise molecular mechanisms involved in this requires further investigation. Earlier studies revealed that microRNAs (miRNAs) play a significant role in regulating the functions of decidual stromal and trophoblast cells. Although there are few studies on the intervention of malfunctioning dNK cells, this strategy shows promise in regulating abnormal miRNA production in NK cells. This study confirmed miR-122-5p downregulation in dNK cells from patients experiencing unexplained RPL. miR-122-5p regulates apoptosis, inflammatory factor secretion, and cytotoxicity of NK cells. miR-122-5p may contribute to immune tolerance at the maternal-fetal interface by targeting transcription factor T-bet. This study provides a deeper understanding of the mechanisms by which miR-122-5p regulates the function of dNK cells and trophoblasts at the maternal-fetal interface to ensure successful pregnancy.
在妊娠早期,母体-胎儿界面富含自然杀伤 (NK) 细胞,这些细胞释放生长因子以支持胎儿发育并促进子宫螺旋动脉重塑。先前的研究表明,异常的蜕膜自然杀伤 (dNK) 细胞频率和活性与复发性妊娠丢失 (RPL) 有关。各种因素调节 dNK 细胞的作用及其与滋养层细胞的相互作用,以促进半同种异体胚胎的定植和成熟。然而,要了解涉及其中的确切分子机制还需要进一步研究。早期研究表明,微小 RNA (miRNA) 在调节蜕膜基质和滋养层细胞的功能方面发挥着重要作用。尽管关于干预功能失调的 dNK 细胞的研究较少,但这种策略在调节 NK 细胞中异常 miRNA 产生方面显示出了希望。本研究证实了不明原因 RPL 患者的 dNK 细胞中 miR-122-5p 下调。miR-122-5p 调节 NK 细胞的凋亡、炎症因子分泌和细胞毒性。miR-122-5p 可能通过靶向转录因子 T-bet 来促进母体-胎儿界面的免疫耐受。本研究更深入地了解了 miR-122-5p 调节 dNK 细胞和滋养层细胞在母体-胎儿界面功能的机制,以确保成功妊娠。