Devvanshi Himadri, Kachhwaha Rohit, Manhswita Anima, Bhatnagar Shinjini, Kshetrapal Pallavi
Maternal and Child Health, Translational Health Science and Technology Institute, Faridabad, India.
School of Agriculture and Food Science, The University of Queensland, Brisbane, QLD, Australia.
Front Pharmacol. 2022 Apr 20;13:895254. doi: 10.3389/fphar.2022.895254. eCollection 2022.
Stringent balance of the immune system is a key regulatory factor in defining successful implantation, fetal development, and timely parturition. Interference in these primary regulatory mechanisms, either at adolescence or prenatal state led to adverse pregnancy outcomes. Fertility restoration with the help of injectable gonadotrophins/progesterone, ovulation-inducing drugs, immunomodulatory drugs (corticosteroids), and reproductive surgeries provides inadequate responses, which manifest its own side effects. The development of a potential diagnostic biomarker and an effectual treatment for adverse pregnancy outcomes is a prerequisite to maternal and child health. Parent cell originated bi-layered-intraluminal nano-vesicles (30-150 nm) also known as exosomes are detected in all types of bodily fluids like blood, saliva, breast milk, urine, etc. Exosomes being the most biological residual structures with the least cytotoxicity are loaded with cargo in the form of RNAs (miRNAs), proteins (cytokines), hormones (estrogen, progesterone, etc.), cDNAs, and metabolites making them chief molecules of cell-cell communication. Their keen involvement in the regulation of biological processes has portrayed them as the power shots of cues to understand the disease's pathophysiology and progression. Recent studies have demonstrated the role of immunexosomes (immunomodulating exosomes) in maintaining unwavering immune homeostasis between the mother and developing fetus for a healthy pregnancy. Moreover, the concentration and size of the exosomes are extensively studied in adverse pregnancies like preeclampsia, gestational diabetes mellitus (GDM), and preterm premature rupture of membrane (pPROMs) as an early diagnostic marker, thus giving in-depth information about their pathophysiology. Exosomes have also been engineered physically as well as genetically to enhance their encapsulation efficiency and specificity in therapy for cancer and adverse pregnancies. Successful bench to bedside discoveries and interventions in cancer has motivated developmental biologists to investigate the role of immunexosomes and their active components. Our review summarizes the pre-clinical studies for the use of these power-shots as therapeutic agents. We envisage that these studies will pave the path for the use of immunexosomes in clinical settings for reproductive problems that arise due to immune perturbance in homeostasis either at adolescence or prenatal state.
免疫系统的严格平衡是决定成功着床、胎儿发育和适时分娩的关键调节因素。在青春期或产前状态对这些主要调节机制的干扰会导致不良妊娠结局。借助注射用促性腺激素/孕酮、促排卵药物、免疫调节药物（皮质类固醇）和生殖手术来恢复生育能力，效果并不理想，且会产生自身的副作用。开发潜在的诊断生物标志物和针对不良妊娠结局的有效治疗方法是母婴健康的先决条件。母细胞起源的双层腔内纳米囊泡（30 - 150纳米），也被称为外泌体，在血液、唾液、母乳、尿液等所有类型的体液中都能检测到。外泌体是细胞毒性最小的生物残留结构，其携带的物质包括RNA（微小RNA）、蛋白质（细胞因子）、激素（雌激素、孕酮等）、互补DNA和代谢物，使其成为细胞间通讯的主要分子。它们积极参与生物过程的调节，这使其成为理解疾病病理生理学和进展的关键线索。最近的研究表明免疫外泌体（免疫调节外泌体）在维持母亲与发育中的胎儿之间稳定的免疫稳态以实现健康妊娠方面发挥着作用。此外，在子痫前期、妊娠期糖尿病（GDM）和胎膜早破（pPROMs）等不良妊娠中，对外泌体的浓度和大小进行了广泛研究，将其作为早期诊断标志物，从而深入了解其病理生理学。外泌体还通过物理和基因工程进行改造，以提高其在癌症和不良妊娠治疗中的包封效率和特异性。癌症领域从实验室到临床的成功发现和干预激发了发育生物学家去研究免疫外泌体及其活性成分的作用。我们的综述总结了将这些关键物质用作治疗剂的临床前研究。我们设想这些研究将为免疫外泌体在临床环境中用于治疗因青春期或产前状态下免疫稳态紊乱而出现的生殖问题铺平道路。
