Upregulation of Circulating MiR-211 and MiR-744 is Related to Postpartum Depression via Estrogen Receptor 1 Targeting

Abstract

Background and Objective: Postpartum depression (PPD), a severe psychiatric disorder, affects more than 10% of women worldwide. Traditional screening for depression cannot identify patients without a history of mood disorders. This study aimed to identify new candidate biomarkers in exosomes isolated from peripheral blood and explore their function in patients with PPD. Methods: Forty-four patients with PPD and 20 healthy controls were recruited fofr plasma collection. Isolation of extracellular vesicles (EVs) was confirmed by immunoblotting and transmission electron microscopy. Five candidate miRNAs in exosomes were quantified using quantitative reverse transcription PCR (RT-qPCR). Genes repressed by the miRNAs (microRNAs) were identified using a luciferase assay. Results: The levels of miR-211 and miR-744 in plasma exosomes were significantly upregulated in patients with PPD. MiR-211 interacted with the mRNAs of estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2), and repressed their expression. miR-744 can inhibit ESR1 expression but not that of ESR2. Upregulation of miR-211 and miR-744 inhibited estradiol (E2) signaling and repressed the expression of downstream genes including brain-derived neurotrophic factor (BDNF) and cyclin D1 (CCND1). Bioinformatic analysis indicated that 85 genes were directly targeted by both miR-211 and miR-744. These potential target genes were enriched in neuron differentiation, nervous system, and miRNA function. ESR1, SRY-box transcription factor 11 (SOX11), BDNF, EPH receptor B2 (EPHB2), and argonaute 3 (AGO3) were the hub genes in the gene ontology map. Conclusions: The expression of miR-211 and miR-744 was upregulated in exosomes from patients with PPD, which may contribute to the development of PPD by targeting ESR1 and ESR2.