Meta-analysis of endometrial transcriptome data reveals novel molecular targets for recurrent implantation failure.

PURPOSE: Gene expression analysis of the endometrium has been shown to be a useful approach for identifying the molecular signatures and pathways involved in recurrent implantation failure (RIF). Nevertheless, individual studies have limitations in terms of study design, methodology and analysis to detect minor changes in expression levels or identify novel gene signatures associated with RIF. METHOD: To overcome this, we conducted an in silico meta-analysis of nine studies, the systematic collection and integration of gene expression data, utilizing rigorous selection criteria and statistical techniques to ensure the robustness of our findings. RESULTS: Our meta-analysis successfully unveiled a meta-signature of 49 genes closely associated with RIF. Of these genes, 38 were upregulated and 11 downregulated in RIF patients' endometrium and believed to participate in key processes like cell differentiation, communication, and adhesion. GADD45A, IGF2, and LIF, known for their roles in implantation, were identified, along with lesser-studied genes like OPRK1, PSIP1, SMCHD1, and SOD2 related to female infertility. Many of these genes are involved in MAPK and PI3K-Akt pathways, indicating their role in inflammation. We also investigated to look for key miRNAs regulating these 49 dysregulated mRNAs as potential diagnostic biomarkers. Along with this, we went to associate protein-protein interactions of 49 genes, and we could recognize one cluster consisting of 11 genes (consisted of 22 nodes and 11 edges) with the highest score (p = 0.001). Finally, we validated some of the genes by qRT-PCR in our samples. CONCLUSION: In summary, the meta-signature genes hold promise for improving RIF patient identification and facilitating the development of personalized treatment strategies, illuminating the multifaceted nature of this complex condition.

Dysfunctional regulation of pivotal and key inflammatory pathways in infertile Indian women with genital tuberculosis.

PROBLEM: Diagnosis of female genital tuberculosis (FGTB) remains elusive due to the paucibacillary nature of the disease. We evaluated if analysis of inflammatory pathways of endometrial tissue could establish a better diagnosis of FGTB. METHOD OF STUDY: One hundred and four infertile women suspected of having GTB or having been treated for GTB in the past, underwent endometrial biopsies for diagnosis and Gene Inflammatory Pathways analysis at our center between 2018-2020. Diagnosis of FGTB was based on acid-fast bacilli culture, immunocytochemistry, nested-polymerase chain reaction, histopathological examination, TB GeneXpert, or combinations thereof. Gene expression profiles were also analyzed. RESULTS: Based on diagnostic tests of 104 women, 44 (42%) were considered TB-positive, 35 (34%) TB-negative, and 25 (24%) TB-negative after TB treatment in the past. Inflammatory pathways were significantly upregulated in TB-positive women versus TB-negative (41% vs. 6%; p = .0005), and in women who were TB-negative after TB treatment in the past versus TB-negative (never treated for TB in the past) (38% vs. 6%; p = .0037). Two-hundred seventy-one genes were upregulated, and 61 genes were downregulated in TB-positive women versus those who were TB-negative. Differentially expressed genes were mapped to various interlinked inflammatory signaling pathways, including mitogen-activated protein kinase (MAPK), Natural Killer (NK) cells, nuclear factor kappa-B (NF-kB), tumor necrosis factor (TNF), and Toll-like receptors (TLR) signaling. CONCLUSIONS: Inflammatory pathways and gene expression profiles add to the diagnostic tools to identify TB-positive women at an early stage. The results from this study are still experimental and large multi-centric studies are suggested before their recommendation in routine clinical practice.