Identification of global transcriptome abnormalities and potential biomarkers in eutopic endometria of women with endometriosis: A preliminary study

Abstract

The etiology and pathophysiology of endometriosis remain unclear. The aim of the current study was to identify a candidate pathogenic gene, as well as potential biomarkers of endometriosis using messenger RNA (mRNA) sequencing (mRNA-seq). Twenty-three eutopic endometria from women with endometriosis and 20 endometria from control subjects were investigated. Eight eutopic endometria and five normal endometria were selected for mRNA-seq. Differentially expressed genes (DEGs) were identified and functional analysis was conducted. Validation of certain DEGs was performed in the remaining cases and control subjects by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 72 DEGs (66 upregulated and 6 downregulated) were identified in samples from women with endometriosis and compared with the control subjects. High DEGs included those involved in various functions, such as extracellular matrix (ECM) remodeling, angiogenesis, cell proliferation and differentiation. Enriched by these DEGs, 100 Gene Ontology terms were identified as significantly important, particularly ‘ECM’ and ‘endogenous stimulus’. Validation using RT-qPCR indicated that matrix metallopeptidase 11, dual specificity phosphatase 1, Fos proto-oncogeneand serpin family E member 1 were significantly upregulated and adenosine deaminase 2 was significantly downregulated in the eutopic endometrium of patients with endometriosis. The identified DEGs may be involved in the pathogenesis of endometriosis and may be potential biomarkers in the eutopic endometrium. The current study provides a comprehensive, but preliminary insight for elucidating the mechanisms of endometriosis, which require further in-depth studies for confirmation.

Regulation of Inflammation Pathways and Inflammasome by Sex Steroid Hormones in Endometriosis

“…Different transcriptomic alterations have been detected in endometriosis patients; for example, by using cDNA microarray analysis specific genes that mainly encode components of the immune system and inflammatory pathways, proteins involved in cell adhesion and remodeling of the extracellular matrix as well components of signal transduction pathways were found differentially expressed in ectopic endometrium when compared to eutopic endometrium; some altered genes are those that encode phospholipase A2 group IIA (PLA2 IIA), PLA2 group V (PLA2 V), fatty acid-binding protein 4 (FABP4), prostacyclin synthase (PGIS), complement component 7, claudin 11, heptoglobin, some integrins, and tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) (44). Furthermore, next-generation sequencing analysis of eutopic endometrium transcriptome has shown abnormalities in comparison with endometrium from healthy women, demonstrating differential expression of genes involved in extracellular matrix remodeling, angiogenesis, cell proliferation and differentiation, such as matrix metallopeptidase 11 (MMP-11), dual specific phosphatase 1 (DUSP1), Fos proto-oncogene (FOS), serpin family E member 1 (SERPINE1), and adenosine deaminase 2 (ADA2) (45).…”

Molecular-genetic background of endometriosis: diagnostic potential of heritable and expressed factors

“…к сожалению, число таких исследований край-не ограничено, что не позволяет провести мета-анализ данных и оценить воспроизводимость полученных результатов. Так, безупречное с точки зрения дизайна, но пока единствен-ное в своем роде исследование было проведе-но китайской научной группой [25]. Ученые исследовали восемь образцов эутопического эндометрия женщин с гистологически вери-фицированным эндометриозом III-IV стадий и пять образцов эндометрия здоровых женщин.…”

“…Уровень экспрессии обо-значен цветом. Воспроизведен с согласия издатель-ства и соблюдением лицензионных соглашений из [25] fig. 1.…”

“…The expression levels are indicated using colors. Reproduced by the authors with the consent of the publisher and subject to license agreements from [25] [25]. Другое аналогичное исследование было про-ведено американской научной группой [26].…”

The Role of Biomarkers in the Early Diagnosis of Endometriosis

“…This inevitably leads to major disability and impaired quality of life. Indeed due to the nature of this condition many women may mistakenly think the symptoms they suffer are normal [3].…”