Integrated single-cell RNA-seq and DNA methylation reveal the effects of air pollution in patients with recurrent spontaneous abortion

Abstract

Background Maternal air pollutants exposure is associated with a number of adverse pregnancy outcomes, including recurrent spontaneous abortion (RSA). However, the underlying mechanisms are still unknown. The present study aimed to understand the mechanism of RSA and its relationship with air pollution exposure. We compared data of decidual tissue from individuals with induced abortions and those with RSA by bulk RNA sequencing (RNA-seq), reduced representation bisulfite sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq). Differentially expressed genes (DEGs) were verified using RT-qPCR and pyrosequencing. A logistic regression model was used to investigate the association between air pollutants exposure and RSA. Results We identified 98 DEGs with aberrant methylation by overlapping the RRBS and RNA-seq data. Nineteen immune cell subsets were identified. Compared with normal controls, NK cells and macrophages accounted for different proportions in the decidua of patients with RSA. We observed that the methylation and expression of IGF2BP1 were different between patients with RSA and controls. Furthermore, we observed significant positive associations between maternal air pollutants exposure during the year prior to pregnancy and in early pregnancy and the risk of RSA. Mediation analyses suggested that 24.5% of the effects of air pollution on the risk of RSA were mediated through IGF2BP1 methylation. Conclusion These findings reveal a comprehensive cellular and molecular mechanism of RSA and suggest that air pollution might cause pregnancy loss by affecting the methylation level of the IGF2BP1 promoter.

A new "single" era of biomedicine and implications in disease research

“…All in all, in the new era of biomedicine, more novel techniques and related applications will help us to get more discoveries and breakthroughs. [151][152][153] In fact, a next-generation sequencing from RNA-seq to scRNA-seq, in particular combined with GWAS and/or DNA methylation analysis, [154][155][156] will identify novel susceptibility loci, reveal molecular characteristics and comprehensive cellular and molecular mechanisms. Different from whole-exome sequencing, [157,158] this new targeted and next-generation sequencing at the SC level, [159][160][161] that is scRNA-seq, [162][163][164] will definitely help to screen, diagnose, and treatment of CHD, [165] COVID, [166] and others.…”

The impact of DNA methylation as a factor of Adverse Pregnancy and Birth Outcomes (APBOs): a systematic review protocol

“…Adverse pregnancy and birth outcomes (APBOs) including miscarriage, Low birth weight (LBW), preterm birth (PTB), sepsis, and intrauterine growth restriction (IUGR) are major public health problems and have been linked with a high risk of mortality and morbidities during both the neonatal period and later in life [ 1 – 4 ]. The majority of these APBOs are associated with maternal exposure to genetic and environmental factors during pregnancy.…”

SLC8A1, a novel prognostic biomarker and immunotherapy target in RSA and UCEC based on scRNA-seq and pan-cancer analysis

“…Zhu et al conducted a comprehensive analysis of decidual tissue data obtained from individuals who underwent induced abortions and those with recurrent spontaneous abortion (RSA). This analysis involved the use of bulk RNA sequencing (RNAseq), reduced representation bisul te sequencing (RRBS), and single-cell RNA sequencing (scRNA-seq) [13]. The ndings of this study revealed that a thorough understanding of the cellular and molecular mechanisms underlying RSA can be achieved, with a particular focus on the potential impact of IGF2BP1 promoter methylation on pregnancy loss.…”