Abstract
Recurrent spontaneous abortion (RSA) remains a critical and challenging problem in reproduction. To discover novel biomarkers for RSA, ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) metabolomics approach was applied to detect RSA serum metabolic profiles and explore its possible pathogenesis and mechanism. The abortion rat model was established, and a metabolomics analysis was performed to evaluate the differentially expressed metabolites between the control and model groups. Immunohistochemistry (IHC), qRT-PCR, and Western blot further examined the expression of Arachidonic acid metabolism-related genes in uterus tissues. To identify arachidonic acid metabolism-related changes in RSA, ELISA’s potential mechanisms were further confirmed in serum. Ninety-one metabolites were significantly different between the two groups, as indicated by a VIP ≥1, fold change ≥1. The metabolic pathways involving arachidonic acid metabolism pathway (P = 0.00044) are related to RSA. Verification by experimental showed that compared with the control rats, the expression of the COX-1, COX-2, PTGFR, and TBXA2R genes associated with the arachidonic acid metabolism pathway has significantly increased the uterus and serum of RSA rats (P < 0.05). Regulation of the arachidonic acid metabolism pathway might serve as a promising therapeutic strategy for relieving RSA women’s symptoms.
Highlights
Natural abortion occurs in 10% of women with normal pregnancy, and recurrent spontaneous abortion (RSA) accounts for about 5% [1]
All of the results indicate that the repeatability and stability of the proposed method were statistically acceptable
This result confirms that the significant differences observed between the two groups using multivariate statistical analysis were more likely to result from genuine metabolites’ changes rather than from technical errors
Summary
Natural abortion occurs in 10% of women with normal pregnancy, and recurrent spontaneous abortion (RSA) accounts for about 5% [1]. Mechanism in Recurrent Spontaneous Abortion women who have had an abortion experience have a risk of up to 75% in the second pregnancy, which seriously affects patients’ physical and mental health. Approximately 50% of RSA causes remain unknown. Human normal physiological activities will produce specific metabolites, but the metabolism may damage maternal and fetal health in some pregnant women [15]. There is a lack of systematic study on serum metabolites and markers of recurrent abortion. Metabolomics has rarely been used to identify novel metabolic biomarkers for RSA, and since the specific pathogenesis of RSA remains unclear, this valuable tool can be used as a means to reveal its underlying etiology
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