Circular RNAs: Novel potential regulators in embryogenesis, female infertility, and pregnancy‐related diseases

Abstract

Circular RNAs (circRNAs) are endogenous noncoding RNAs with unique cyclic structures. Although they were previously considered as nonfunctional transcription byproducts, numerous studies have demonstrated that circRNAs regulate gene transcription and expression via different mechanisms. Reproductive health influences the quality of life and affects offspring propagation in women. CircRNAs have been found to modify pregnancy‐related diseases, gynecologic cancers, polycystic ovary syndrome, aging, gamete, and embryo development. It's promising for circRNAs to be the novel diagnostic and therapeutic targets for multiple reproductive diseases. With the widespread application of assisted reproduction technology (ART), it has been revealed that circRNA identification contributes to estimating the quality of gametes and embryos, reflecting the success rate of ART. CRISPR‐Cas9 gene editing technology has enabled the discovery of new roles of circRNAs. So far, the roles of circRNAs in the reproductive system remain poorly defined. In this review, we describe the classification and functions of circRNAs in embryogenesis and the female reproductive system diseases, revealing potential roles of circRNAs physiologically and pathologically. In so‐doing, we provide ideas for developing circRNA‐based therapeutic treatment and clinical application of various female reproductive system diseases.

CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR‐136‐3p/IGF2R axis

“…24 The advancement of high-throughput sequencing has led to the discovery of numerous circRNAs, which have been found to play a role in disease progression. 25,26 However, the investigation of circRNAs in the context of FGR remains limited. Given the conserved and stable characteristics of circRNAs, they possess great potential as biomarkers for disease diagnosis.…”

“…The crucial role of placental trophoblastic cells in pregnancy and embryonic development is widely recognized, and the research on the pathogenesis of FGR has specifically emphasized their invasive function 24 . The advancement of high‐throughput sequencing has led to the discovery of numerous circRNAs, which have been found to play a role in disease progression 25,26 . However, the investigation of circRNAs in the context of FGR remains limited 27,28 .…”

The Circ-CYP24A1-miR-224-PRLR Axis Impairs Cell Proliferation and Apoptosis in Recurrent Miscarriage

“…It has been reported that circRNAs are significantly involved in regulating cell proliferation, apoptosis, and differentiation ( Jia and Li, 2019 ; Chen et al, 2021 ; Gao et al, 2021 ; Sun et al, 2021 ). High levels of circRNA_33186 have been reported to promote apoptosis and inhibit proliferation in osteoarthritis ( Zhou et al, 2019 ).…”

Circular RNA in disease: Basic properties and biomedical relevance

“…Endometrial fibrosis, endometriosis‐associated infertility, and pre‐eclampsia (PE) are some of the most common gynecological diseases worldwide, and the association of circRNAs with those diseases has been revealed (Gao et al, 2021; Koninckx et al, 2019; Yu et al, 2008; Table 3). CircPTPN12 is up‐regulated in endometrial epithelial cells (EECs) of fibrotic endometrium, and elevates the expression of DeltaNp63alpha by sponging miR‐21‐5p to induce the epithelial–mesenchymal transition (EMT) of EECs (M. Song, Zhao, et al, 2021).…”