What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

Abstract

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial–mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

LGALS2 and EGR1: markers of endometriosis for predictive, preventive and personalized medicine

“…According to previous research, Egr1, a transcription factor, interacts with CAIX and is necessary for endometrial stromal cell proliferation, migration, and invasion [42]. The present study shows that EGR1 expression is much higher in ectopic endometrium than eutopic endometrium and in normal individuals, which is consistent with Penariol's work [43]. This indicatess that EGR1 may play a role in the etiology of EM by influencing the balance of endometrial stromal cell proliferation and apoptosis.…”

Downregulation of DROSHA: Could It Affect miRNA Biogenesis in Endometriotic Menstrual Blood Mesenchymal Stem Cells?

“…Our group recently published the first study that integrated transcriptome and proteome data in endometriotic MenSCs; of note, we found no major changes in these two different landscapes [ 17 ]. Thus, DROSHA compensatory mechanisms may be acting in these progenitor cells, making it favorable to study miRNoma under these experimental conditions to profile the miRNAs in these cells to understand the mechanisms involved in the disease.…”

“…In addition, given the important particularities evidenced in the endometrium of women with endometriosis [ 13 , 14 ], and although the participation of the endometrium as a carrier of changes is not fully understood, tracking molecular alterations in these progenitor cell types could demonstrate their involvement in the disease. The few studies on differential expression of genes or proteins in endometriotic MenSCs suggest that primary cell alterations are related to impaired decidualization potential and the chronic inflammatory endometrial microenvironment [ 15 , 16 , 17 , 18 ].…”

Uterine Transcriptome: Understanding Physiology and Disease Processes

“…Simultaneously discovering these progenitor cells, several approaches such as genomics, epigenomics, transcriptomics, and proteomics have been applied to better understand physiologic and pathologic conditions associated with human endometrium. The new ‘–omics’ technology has emphasized understanding and characterizing ways to identify the transcriptomic physiological profile in each menstrual cycle [ 9 ], assessing endometrial profiles of fertile patients, i.e., endometrial receptivity window [ 10 ], and those with infertility or recurrent implantation failure [ 11 , 12 ]; and finally, comparisons of profiles between healthy women and women with endometrial pathologies such as endometriosis, adenomyosis, and endometrial cancer [ 13 , 14 , 15 ].…”