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.