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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1397633

Proteomics Profiling Reveals Lipid Metabolism Abnormalities During Oogenesis in Unexplained Recurrent Pregnancy Loss

Provisionally accepted
Kun Liu Kun Liu 1*Xiaojuan Xu Xiaojuan Xu 1Liang Sun Liang Sun 1Hongxing Li Hongxing Li 1Yi Jin Yi Jin 1Xiaoling Ma Xiaoling Ma 1Bairong Shen Bairong Shen 2*Cesar Martin Cesar Martin 3*
  • 1 First Hospital of Lanzhou University, Lanzhou, China
  • 2 West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
  • 3 University of the Basque Country, Bilbao, Basque Country, Spain

The final, formatted version of the article will be published soon.

    Background: Unexplained recurrent pregnancy loss (URPL) is a clinical dilemma in reproductive fields. Its diagnosis is mainly exclusionary after extensive clinical examination, and some of the patients may still face the risk of miscarriage.We analyzed follicular fluid (FF) from in vitro fertilization (IVF) in eight patients with URPL without endocrine abnormalities or verifiable causes of abortion and eight secondary infertility controls with no history of pregnancy loss who had experienced at least one normal pregnancy and delivery by direct data independent acquisition (dDIA) quantitative proteomics to identify differentially expressed proteins (DEPs). In this study, bioinformatics analysis was performed using online software including g:profiler, String, and ToppGene.Cytoscape was used to construct the protein-protein interaction (PPI) network, and ELISA was used for validation.Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEPs are involved in the biological processes (BP) of complement and coagulation cascades.Apolipoproteins (APOs) are key proteins in the PPI network. ELISA confirmed that APOB was low-expressed in both the FF and peripheral blood of URPL patients.Dysregulation of the immune network intersecting coagulation and inflammatory response is an essential feature of URPL, and this disequilibrium exists as early as the oogenesis stage. Therefore, earlier intervention is necessary to prevent the development of URPL. Moreover, aberrant lipoprotein regulation appears to be a key factor contributing to URPL. The mechanism by which these factors are involved in the complement and coagulation cascade pathways remains to be further investigated, which also provides new candidate targets for URPL treatment.

    Keywords: DDIA, Recurrent pregnancy loss, human follicular fluid, apolipoprotein, biomarkers * E2, estradiol; P, Progesterone

    Received: 04 Apr 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Liu, Xu, Sun, Li, Jin, Ma, Shen and Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Kun Liu, First Hospital of Lanzhou University, Lanzhou, China
    Bairong Shen, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610000, Sichuan Province, China
    Cesar Martin, University of the Basque Country, Bilbao, 48940, Basque Country, Spain

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