Research Projects

Endometriosis (EM) and adenomyosis (AM) are estrogen-dependent uterine disorders affecting approximately 10% and 1% women of reproductive age globally, respectively (Gajbhiye et al, 2021; Munshi, et al, 2025; Mishra et al, 2023). While EM is characterized by the ectopic endometrial lesions outside the uterus (Sampson, 1927; Suginami, 1991; Jerman and Hey-Cunningham, 2015), in AM the lesions form within the uterine myometrium (Rossi et al, 2022). Despite distinct lesion location, both disorders share similar clinical symptoms such as dysmenorrhea, chronic pelvic pain, and infertility (Rossi et al, 2022; Bulun et al, 2021). Notably, women with EM often exhibit concurrent AM, with 6% prevalence in subfertile women (Mishra et al, 2023). Substantial evidence shows that eutopic endometrium (EE) in both disorders differs from healthy controls. In EM, EE had higher natural killer T cells and upregulation of the PI3K and focal adhesion pathways (Poli-Neto et al, 2020; Méar et al, 2022). In AM, EE had higher macrophage and lymphocytes, altered inflammatory signals, platelet aggregation and elevated estradiol level (Bourdon et al, 2021). Only two studies have compared endometrium in EM and AM- one found KRAS mutations in EE of both disorders (Bulun et al, 2021), and another reported PI3K pathway enrichment in DIE and RAS pathway in AM, although tissue source (eutopic or ectopic) was unspecified (Marshall et al, 2023). No study has yet investigated etiopathogenesis, cellular heterogeneity and cell type and cell state specific transcriptional programmes between EM and AM using single-cell transcriptomics in the same settings. Although two reviews highlight differences between EM and AM (Giudice et al, 2025, Li et al, 2024), their findings may be confounded by varying menstrual cycle stages. We hypothesize that EE of adenomyosis, adenomyosis with endometriosis and endometriosis exhibits distinct cellular compositions and disease-specific transcriptional programmes compared to healthy controls. To identify altered cell types and cell states across the conditions, we will perform single-cell transcriptomic profiling of EE from AM (N=5), AM with EM (N=5), EM (N=5) and healthy controls (N=5) in proliferative phase. To determine whether the evolution of cell states alter across conditions, we will perform pseudotime trajectory analysis based on their gene activity. Differential gene expression and pathway analysis will be conducted to uncover biological pathways enriched in each cell type and cell state across different conditions. In additional ten samples per group, we will validate predominant cell types using flow cytometry, and confirm cell-type specific differentially expressed genes using flow cytometry and real time quantitative polymerase chain reaction. This study will provide novel insights into the pathogenesis of EM and AM which have same tissue of origin–endometrium, and will guide to design targeted interventions in terms of therapeutics.