Stromal fibroblasts exhibit a similar transcriptome to mesenchymal stem cells in the perimenopausal endometrium

Mesenchymal stem cells (eMSC) from perimenopausal (PeriM) endometrium do not exhibit significantly different transcriptomes from their premenopausal (PreM) counterparts, but PeriM endometrial stromal fibroblasts (eSF) demonstrate altered pathway activation.We compared transcriptomes of PeriM and PreM eSF, investigated if eMSC persist in PeriM endometrium, and whether eMSC and eSF undergo changes as a result of the perimenopausal endocrine milieu.Endometrium was obtained from 9 PeriM and 9 PreM women. Microarray analysis was performed on FACS-isolated eSF and eMSC and data were validated by quantitative RT-PCR. eMSC were immuofluorescently localized to the perivascular region of PeriM endometrium.Principal component analysis showed that cells clustered into three distinct groups in 3-dimensional space: PeriM eMSC and PreM eMSC clustered together, while PeriM eSF and PreM eSF formed two discrete clusters separate from eMSC. Hierarchical clustering revealed a branching pattern consistent with the PCA results, indicating that eMSC from PreM and PeriM women exhibited a similar transcriptomic signature. Pathway analysis revealed dysregulation of cytoskeleton, proliferation, and survival pathways in PeriM vs. PreM eSF. A number of small nucleolar RNAs were also differentially regulated in PeriM eSF.Cell populations have altered gene expression in PeriM vs. PreM endometrium. While eMSC populations exhibited similar transcriptomes, PeriM eSF had altered pathway activation when compared to PreM eSF. This study provides insight into aging endometrium with relevance to function, including pregnancy establishment in reproductively older women.

33