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Maternal Circulating Exosomal miR-185-5p as Non-invasive Biomarker for the Prediction of Recurrent Pregnancy Loss.

ABSTRACT: Pregnancy losses usually happening suddenly and are irreversible, this study aims to find a predictive biomarker of the upcoming pregnancy loss. We collected serum exosomes from pregnant women prospectively from 6 to 8 weeks gestation and divided the patients into ongoing pregnancy (OP) group, sporadic pregnancy loss (SPL) group, and recurrent pregnancy loss (RPL) group according to the pregnancy progress and pregnancy history. Then we performed genome-wide miRNA expression profiling by small RNA sequencing to identify differences between patients who are going to lose pregnancy and who would not. The results showed there were 68 miRNAs differently expressed among three groups. When comparing RPL group with OP group, there was a set of 43 miRNAs differentially expressed including 25 miRNAs up-regulated in the RPL group and 18 miRNAs down-regulated. Compared SPL group with OP group, there was a set of 76 miRNAs differentially expressed including 24 miRNAs up-regulated in the SPL group and 52 miRNAs down-regulated. Moreover, we combined RPL group and SPL group into PL group, and then compared PL group with OP group, there were 81 miRNAs expressed differently while 60 were up-regulated and 21 were down-regulated. Our study found that there were significant differences in the expression levels of exosomal miRNAs in peripheral blood between patients who continued pregnancy and those who were about to miscarriage, suggesting that maternal peripheral blood exosomal miRNAs could be used as predictive molecular markers for miscarriage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200122 | GEO | 2024/04/25

REPOSITORIES: GEO

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Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.

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Maternal Circulating Exosomal miR-185-5p as Non-invasive Biomarker for the Prediction of Recurrent Pregnancy Loss.

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