Circular RNAs as a novel class of potential therapeutic and diagnostic biomarkers in reproductive biology/diseases

Abstract

Infertility is a prevalent problem among 10% of people within their reproductive years. Sometimes, even advanced treatment options like assisted reproduction technology have the potential to result in failed implantation. Because of the expected changes in gene expression during both in vitro and in vivo fertilization processes, these methods of assisting fertility have also been associated with undesirable pregnancy outcomes related to infertility. In this aspect, Circular RNAs (circRNAs) play a crucial role as epigenetic modifiers in a wide range of biological and pathological activities, including problems with fertility. CircRNAs are integral pieces in multiple cellular functions, including moving substances within the nucleus, silencing one X chromosome, cell death, the ability of stem cells to differentiate into different cell types, and the process of gene expression inherited from parental genes. Due to the progress made in high-speed gene sequencing, a large amount of circRNA molecules have been detected, revealing their significant functions in diverse biological functions like enhancing testicular development, preserving the differentiation and renewal of spermatogonial cells, and controlling spermatocyte meiosis. Moreover, these non-coding RNAs contribute in different aspects of female reproductive system including pregnancy-related diseases, gynecologic cancers, and endometriosis. In conclusion, there is no denying that circRNAs have immense potential to be used as biomarkers and treatments for reproductive disorders in males and females. In this research, we provide a comprehensive analysis of the multiple circRNAs associated with women's infertility.

Keywords: Circular RNAs; Infertility; Reproductive system.

Fig. 1

CircRNA formation and its importance in biological processes are intricately linked. A Circularization facilitated by RBP. B Circularization through the process of intron pairing. C Circularization occurring using a lariat. D TricRNAs are created when pre-tRNAs undergo the splicing process. E One aspect of this event includes EIciRNAs interacting with U1 small nuclear ribonucleoproteins, which causes an increase in transcription of their parent genes by binding with RNA polymerase II. In addition, a direct link between ciRNAs and the RNA polymerase II complex could potentially contribute to the control of transcription for the parental gene. F Potential substitution method for traditional splicing techniques could be the implementation of the circularization process. G EcircRNAs are able to trap mRNAs. H CircRNAs can sponge miRNAs. I CircRNA itself is capable of being used as a sponge to sequester proteins. J circRNAs possess the capability to carry out the process of translation and yield peptides or proteins as a result

Fig. 2

Major function of circRNA is to control gene expression through the manipulation of pre-messenger RNA processing, specifically concerning intronic circRNAs, ciRNAs, and EIciRNAs. Furthermore, it has the ability to sponge and regulate the levels of miRNAs and proteins, acting as a barrier. Moreover, circRNA is also involved in the process of ribosomal RNA maturation, which controls the translation of proteins. This is achieved through the functions of ciRNA, intronic circRNA, circRNAs, EIciRNAs, and mRNAs

Fig. 3

CircRNAs have a strong connection to embryogenesis and embryo implantation, as they have a major influence on the development of granulosa cells and sperm production

Fig. 4

CircRNA molecules play crucial roles in the processes of spermatogenesis and sperm motility. These circular entities can influence the expression of genes through the process of miRNA sequestration