Biogenesis and function of exosome lncRNAs and their role in female pathological pregnancy

Abstract

Preeclampsia, gestational diabetes mellitus, and recurrent spontaneous abortion are common maternal pregnancy complications that seriously endanger women's lives and health, and their occurrence is increasing year after year with a rejuvenation trend. In contrast to biomarkers found freely in tissues or body fluids, exosomes exist in a relatively independent environment and provide a higher level of stability. As backbone molecules, guidance molecules, and signaling molecules in the nucleus, lncRNAs can regulate gene expression. In the cytoplasm, lncRNAs can influence gene expression levels by modifying mRNA stability, acting as competitive endogenous RNAs to bind miRNAs, and so on. Exosomal lncRNAs can exist indefinitely and are important in intercellular communication and signal transduction. Changes in maternal serum exosome lncRNA expression can accurately and timely reflect the progression and regression of pregnancy-related diseases. The purpose of this paper is to provide a reference for clinical research on the pathogenesis, diagnosis, and treatment methods of pregnancy-related diseases by reviewing the role of exosome lncRNAs in female pathological pregnancy and related molecular mechanisms.

Keywords: abortion; biomarkers; diabetes; exosome lncRNA; gestational; pre-eclampsia; pregnancy.

Figure 1

Biogenesis and identification of exosomes. Fluid and extracellular constituents such as proteins, lipids, metabolites, small molecules, and ions can enter cells, along with cell surface proteins, through endocytosis and plasma membrane invagination. The resulting plasma membrane bud formation in the luminal side of the cell presents with outside-in plasma membrane orientation. Several proteins are implicated in exosome biogenesis and include ESCRT proteins, as well as others that are also used as markers for exosomes (CD9, CD81, CD63, flotillin, ceramide, and Alix). Exosome surface proteins include tetraspanins, integrins, immunomodulatory proteins, and more. Exosomes can contain different types of cell surface proteins, intracellular proteins, RNA, DNA, amino acids, and metabolites (15).

Figure 2

Conceptual summary of supragenomic regulation by lncRNAs Vast and heterogeneous lncRNAs interact broadly with gene regulatory machineries. By providing a supragenomic layer of control built upon genomic and epigenomic processes, lncRNAs modulate many levels of gene regulation, from transcription to protein modification (26).

Figure 3

Exosomes and exosomal noncoding RNAs throughout human gestation (9).