Regulatory roles of non-coding RNAs and m6A modification in trophoblast functions and the occurrence of its related adverse pregnancy outcomes

Abstract

Adverse pregnancy outcomes, such as preeclampsia, gestational diabetes mellitus, fetal growth restriction, and recurrent miscarriage, occur frequently in pregnant women and might further induce morbidity and mortality for both mother and fetus. Increasing studies have shown that dysfunctions of human trophoblast are related to these adverse pregnancy outcomes. Recent studies also showed that environmental toxicants could induce trophoblast dysfunctions. Moreover, non-coding RNAs (ncRNAs) have been reported to play important regulatory roles in various cellular processes. However, the roles of ncRNAs in the regulation of trophoblast dysfunctions and the occurrence of adverse pregnancy outcomes still need to be further investigated, especially with exposure to environmental toxicants. In this review, we analyzed the regulatory mechanisms of ncRNAs and m6A methylation modification in the dysfunctions of trophoblast cells and the occurrence of adverse pregnancy outcomes and also summarized the harmful effects of environmental toxicants. In addition to DNA replication, mRNA transcription, and protein translation, ncRNAs and m6A modification might be considered as the fourth and fifth elements that regulate the genetic central dogma, respectively. Environmental toxicants might also affect these processes. In this review, we expect to provide a deeper scientific understanding of the occurrence of adverse pregnancy outcomes and to discover potential biomarkers for the diagnosis and treatment of these outcomes.

Keywords:

• ncRNAs
• m6A
• trophoblast dysfunctions
• adverse pregnancy outcomes
• environmental toxicants

Acknowledgments

The authors acknowledge Roger O. McClellan, the Editor-in-Chief of Critical Reviews in Toxicology, as well as two anonymous reviewers, for careful reading and very valuable comments. All authors gave final approval and agreed to be accountable for all aspects of work in ensuring that questions relating to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of interest

The affiliations of the authors are listed on the cover page. All individuals who contributed to this manuscript are mentioned as authors or listed in the acknowledgment. The authors have sole responsibility for the preparation, analysis, interpretation, and writing of the content of this manuscript. No potential conflict of interest was reported by the authors. No other individuals or entities had input into the text, and the funders had no roles in the written content. The content of this critical review represents the views and professional opinions of the authors. In addition, the authors have no connection with any legal or regulatory agency related to the contents of this manuscript.

Additional information

Funding

The authors also acknowledge financial support from the Natural Science Foundation of China (NSFC No. 82073589), the Fundamental Research Funds for the Central Universities, Shenzhen Science and Technology Program (No. JCYJ20210324114814038), and Futian Healthcare Research Project (No. FTWS2021009).