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Mechanism of hsa_circ_0069443 promoting early pregnancy loss through ALKBH5/FN1 axis in trophoblast cells
Bai-Xue Li1,2,3,4,5,6, Mei-Yao Wu1,2,3,4,7,5,6, Zhi-Hui Wang1,2,3,4,5,6
1Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China.
Insights
Circular RNAs (circRNAs) like hsa_circ_0069443 are crucial for early pregnancy. A decrease in hsa_circ_0069443 may cause pregnancy loss, highlighting its role in embryo implantation and adhesion.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are recognized for their regulatory roles in trophoblast function and embryonic development.
- Exosomes secreted by trophoblast cells mediate crucial uterus-embryo interactions for successful pregnancy.
Purpose of the Study:
- To investigate the regulatory role of hsa_circ_0069443 in trophoblast cells and its potential link to early pregnancy loss.
- To elucidate the mechanism by which hsa_circ_0069443 influences endometrial cells and embryo implantation.
Main Methods:
- Sequencing and functional experiments were employed to identify and characterize hsa_circ_0069443.
- Trophoblast cell-derived exosomes overexpressing hsa_circ_0069443 were used to assess effects on endometrial cells.
- Interactions between hsa_circ_0069443, ALKBH5, and FN1 were investigated.
Main Results:
- Trophoblast cell-derived exosomes with increased hsa_circ_0069443 promoted endometrial stromal cell migration and invasion.
- hsa_circ_0069443 overexpression facilitated the epithelial-mesenchymal transition (EMT) in endometrial glandular epithelial cells, aiding embryo implantation.
- A decrease in hsa_circ_0069443 was identified as a potential factor in early pregnancy loss.
- hsa_circ_0069443 binds to ALKBH5, influencing m6A levels and regulating FN1 expression via the 0069443/ALKBH5/FN1 axis.
Conclusions:
- hsa_circ_0069443 plays a significant role in promoting embryo implantation and adhesion through its effects on trophoblast and endometrial cells.
- Reduced levels of hsa_circ_0069443 are implicated as a key factor contributing to early pregnancy loss.
- The hsa_circ_0069443/ALKBH5/FN1 axis offers potential as a target for early diagnostic markers for pregnancy loss.
Abstract:
Studies have shown that circRNAs play an important regulatory role in trophoblast function and embryonic development. Based on sequencing and functional experiments, we found that hsa_circ_0069443 can regulate the function of trophoblast cells, and its presence is found in the exosomes secreted by trophoblast cells. It is known that exosomes mediate the interaction between the uterus and embryo, which is crucial for successful pregnancy. We found that trophoblast cell-derived exosomes overexpressing hsa_circ_0069443 promoted the migration and invasion of endometrial stromal cells as well as the EMT process of endometrial glandular epithelial cells, and this process promotes embryo implantation and adhesion, thus proving that a decrease in hsa_circ_0069443 may be the key factor leading to early pregnancy loss. This study also found that hsa_circ_0069443 can bind to the RNA-binding protein demethylase ALKBH5, affecting the overall m6A level of trophoblast cells, and hsa_circ_0069443 and ALKBH5 can regulate the expression level of FN1, verifying the role of the 0069443/ALKBH5/FN1 axis in trophoblast cells and endometrial stromal cells. In summary, this study demonstrates that hsa_circ_0069443 may be a key factor leading to early pregnancy loss, and the regulation of the hsa_circ_0069443/ALKBH5/FN1 axis may provide new insights into early diagnostic markers for early pregnancy loss.
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