Proteomic and functional analysis of proteins related to embryonic development of decidua in patients with recurrent pregnancy loss

Abstract Recurrent pregnancy loss (RPL) is defined as the loss of two or more consecutive pregnancies before the 20 weeks of gestation. Recurrent pregnancy loss affects about 1–2% of couples trying to conceive; however, the mechanisms leading to this complication are largely unknown. Our previous studies using comparative proteomics identified 314 differentially expressed proteins (DEPs) in the placental villous. In this study, we identified 5479 proteins from a total of 34,157 peptides in decidua of patients with early recurrent pregnancy loss (Data are available via ProteomeXchange with identifier PXD023849). Further analysis identified 311 DEPs in the decidua tissue; and 159 proteins were highly expressed while 152 proteins were lowly expressed. These 311 proteins were further analyzed by using Ingenuity Pathway Analysis (IPA). The results suggested that 50 DEPs played important roles in the embryonic development. Upstream analysis of these DEPs revealed that AGT was the most important upstream regulator. Furthermore, protein - protein interaction (PPI) analysis of the embryonic development DEPs from the placental villous and decidua was performed in the STRING database. This study identified several proteins specifically associated with embryonic development in decidua of patients with early recurrent pregnancy loss. Therefore, these results provide new insights into potential biological mechanisms, that may ultimately inform recurrent pregnancy loss.

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Paternal factors and embryonic development: Role in recurrent pregnancy loss

Andrologia ◽

10.1111/and.13171 ◽

2018 ◽

Vol 51 (1) ◽

pp. e13171 ◽

Cited By ~ 3

Author(s):

Vidhu Dhawan ◽

Manoj Kumar ◽

Dipika Deka ◽

Neena Malhotra ◽

Neeta Singh ◽

...

Keyword(s):

Embryonic Development ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Paternal Factors

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Molecular mechanisms of imprinted gene disturbance in the embryonic development pathology and recurrent pregnancy loss

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.11.79-80 ◽

2020 ◽

pp. 79-80

Author(s):

Е.А. Саженова ◽

И.Н. Лебедев

Keyword(s):

Embryonic Development ◽

Pregnancy Loss ◽

Molecular Mechanisms ◽

Recurrent Pregnancy Loss ◽

Gene Mutations ◽

Spontaneous Abortions ◽

Imprinted Gene ◽

Heterozygous Carriers

Установлено, что остановка эмбрионального развития человека сопровождается мультилокусными дефектами метилирования импринтированных генов, частота которых повышена в плацентарных тканях спонтанных абортусов от женщин с привычным невынашиванием беременности. Показано, что множественные дефекты метилирования импринтированных генов сопровождаются мутациями гена NLRP7 у спонтанных абортусов от женщин с привычным невынашиванием беременности, а родители являются гетерозиготными носителями данных мутаций. It was found that disturbances of embryonic development are accompanied by multi-locus imprinting disturbance (MLID), the frequency of which is increased in placental tissues of spontaneous abortions from women with recurrent pregnancy loss. It is shown that MLID are accompanied by NLRP7 gene mutations in spontaneous abortions from women with recurrent pregnancy loss, and parents are heterozygous carriers of these mutations.

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Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction

Clinical Proteomics ◽

10.1186/s12014-021-09312-2 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Xiang-Jie Yin ◽

Wei Hong ◽

Fu-Ju Tian ◽

Xiao-Cui Li

Keyword(s):

Oxidative Stress ◽

Western Blotting ◽

Pregnancy Loss ◽

Molecular Mechanisms ◽

Recurrent Pregnancy Loss ◽

Differentially Expressed ◽

Decidual Cell ◽

Differentially Expressed Proteins ◽

Absolute Quantitation ◽

Cox 2

Abstract Background Pregnancy is a complicated physiological process. The multifaceted regulation of maternal–fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion. However, no significant breakthrough has been made. Therefore, it is important to understand the molecular mechanisms of recurrent pregnancy loss (RPL) to identify potential therapeutic strategies. The aim of this study was to investigate the pathogenesis of RPL. Methods In this study, Relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis was used to identify differentially expressed proteins in decidual from RPL patients and matched normal controls. Further, Molecules NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 (ndufb3) and cyclooxygenase-2 (COX-2) were validated by immunohistochemistry (IHC), Western blotting, CCK8 and mitochondrial red fluorescent probe (Mito-Tracker Red CMXRos). Results A total of 456 proteins reached the threshold of a 1.5-fold change were identified for further bioinformatics analysis. Upon mapping the differentially expressed proteins using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways database, iTRAQ results were confirmed by assessing NDUFB3 and COX-2 protein levels in specimens of decidual tissue by Western blotting. Our study indicates that the level of COX-2 and NDUFB3 were significantly increased in decidual cell from RPL patients. Overexpression of NDUFB3 inhibited cell vitality and oxidative stress of decimal cell. Further, our found that overexpression NDUFBD3 in decidual cell decreased the mitochondrial membrane potential expression levels. These results suggest that NDUFB3 might play an important role in promote the pathological process of RPL. Conclusions This comprehensive analysis of RPL proteomics reveals novel candidate: NDUFB3, which could be further investigated for explanation of the pathological mechanism of RPL.

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Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

10.21203/rs.2.20745/v1 ◽

2020 ◽

Author(s):

Le Huang ◽

Changqiang Wei ◽

Zhao Zhang ◽

Jiao Cen ◽

Zhiwei Zhu ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Early Pregnancy ◽

Regulatory Networks ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Gene Expression Omnibus ◽

Potential Mechanism ◽

Omics Analysis ◽

Key Genes

Abstract BackgroundThe potential mechanism of early recurrent pregnancy loss (ERPL) has not been fully elucidated, a multi-omics analysis can help us find key genes.ResultsWe download data from Gene Expression Omnibus (GEO), 90 hypermethylation-down regulated genes and 49 hypomethylation-up regulated genes were identified by intersection. Compared with the normal early pregnancy group, the expression of ERCC2 and MLH1 was lower in ERPL group, but the expression of PLEK and FOS was higher, and the expression of MLH1 was statistically significant (p<0.05). Compared with the anembryonic (empty sac) miscarriage group, the expression of MLH1, PLEK, FOS decreased, and that of ERCC2 increased in the embryonic miscarriage group. TF-MDEGs networks predicted SP1, POLR2A, YY1, CREM and CREB1 were involved in methylation regulation of DNA promoter with MDEGs. Among them, YY1, FOXP3 and p53 may be related to the mechanism of MLH1 in ERPL.ConclusionsOur study identified possible aberrant MDEGs, and TF- MDEGs regulatory networks may be related to its mechanism. MLH1 may play an important role in early embryonic development.

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Prediction key genes and the potential molecular mechanism for early recurrent pregnancy loss by Multi-Omics analysis

10.21203/rs.3.rs-15435/v1 ◽

2020 ◽

Author(s):

Le Huang ◽

Changqiang Wei ◽

Zhao Zhang ◽

Jiao Cen ◽

Zhiwei Zhu ◽

...

Keyword(s):

Gene Expression ◽

Embryonic Development ◽

Early Pregnancy ◽

Regulatory Networks ◽

Pregnancy Loss ◽

Recurrent Pregnancy Loss ◽

Gene Expression Omnibus ◽

Potential Mechanism ◽

Omics Analysis ◽

Key Genes

Abstract Background: The potential mechanism of early recurrent pregnancy loss (ERPL) has not been fully elucidated, a multi-omics analysis can help us find key genes.Results: We download data from Gene Expression Omnibus (GEO), 90 hypermethylation-down regulated genes and 49 hypomethylation-up regulated genes were identified by intersection. Compared with the normal early pregnancy group, the expression of ERCC2 and MLH1 was lower in ERPL group, but the expression of PLEK and FOS was higher, and the expression of MLH1 was statistically significant (p<0.05). Compared with the anembryonic (empty sac) miscarriage group, the expression of MLH1, PLEK, FOS decreased, and that of ERCC2 increased in the embryonic miscarriage group. TF-MDEGs networks predicted SP1, POLR2A, YY1, CREM and CREB1 were involved in methylation regulation of DNA promoter with MDEGs. Among them, YY1, FOXP3 and p53 may be related to the mechanism of MLH1 in ERPL.Conclusions: Our study identified possible aberrant MDEGs, and TF- MDEGs regulatory networks may be related to its mechanism. MLH1 may play an important role in early embryonic development.

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