Stromal fibroblasts from perimenopausal endometrium exhibit a different transcriptome than those from the premenopausal endometrium

David Erikson, Fatima Barragan, Terhi T. Piltonen, Joseph C. Chen, Shaina Balayan, Juan C. Irwin, Linda C. Giudice

Research output: Contribution to journalArticle

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Abstract

Human endometrium undergoes extensive regeneration on a cyclic basis in premenopausal women and likely occurs through the contribution of stem/progenitor cells. Menopause results in the permanent cessation of menstrual cycles and is preceded by perimenopause, a period of several years in which endocrine and biological changes occur and is a period of risk for endometrial proliferative disorders. The objectives of this study were to identify endometrial mesenchymal stem cells (eMSC) and endometrial stromal fibroblasts (eSF) in endometrium of perimenopausal women and perform expression profile analysis of perimenopausal eMSC and eSF to gain insight into the biology of stem/progenitor and lineage cell populations during the transition to menopause. Endometrial tissue was collected from perimenopausal and premenopausal women (n = 9 each). Microarray analysis was performed on fluorescence-activated cell sorting-isolated eSF and eMSC, and data were validated by quantitative real-time PCR. Principal component analysis showed that cells clustered into three distinct groups in 3-dimensional space: perimenopausal eMSC and premenopausal eMSC clustered together, while perimenopausal eSF and premenopausal eSF formed two discrete clusters separate from eMSC. Hierarchical clustering revealed a branching pattern consistent with principle clustering analysis results, indicating that eMSC from premenopausal and perimenopausal women exhibit similar transcriptomic signatures. Pathway analysis revealed dysregulation of cytoskeleton, proliferation, and survival pathways in perimenopausal vs. premenopausal eSF. These data demonstrate that cell populations have altered gene expression in perimenopausal vs. premenopausal endometrium, and that perimenopausal eSF had altered pathway activation when compared to premenopausal eSF. This study provides insight into aging endometrium with relevance to function in reproductively older women. Summary Sentence The hormonal milieu during the transition to menopause has an effect on endometrial stromal fibroblast gene expression and a minimal effect on the endometrial mesenchymal stem cell population, offering insight into the mechanisms by which the endometrium remains functional after menopause.

Original languageEnglish (US)
Pages (from-to)387-399
Number of pages13
JournalBiology of Reproduction
Volume97
Issue number3
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

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Endometrium
Transcriptome
Mesenchymal Stromal Cells
Fibroblasts
Menopause
Stem Cells
Cluster Analysis
Perimenopause
Population
Gene Expression
Microarray Analysis
Menstrual Cycle
Principal Component Analysis
Cytoskeleton
Real-Time Polymerase Chain Reaction
Regeneration
Flow Cytometry
Survival

ASJC Scopus subject areas

  • Cell Biology

Cite this

Erikson, D., Barragan, F., Piltonen, T. T., Chen, J. C., Balayan, S., Irwin, J. C., & Giudice, L. C. (2017). Stromal fibroblasts from perimenopausal endometrium exhibit a different transcriptome than those from the premenopausal endometrium. Biology of Reproduction, 97(3), 387-399. https://doi.org/10.1093/biolre/iox092

Stromal fibroblasts from perimenopausal endometrium exhibit a different transcriptome than those from the premenopausal endometrium. / Erikson, David; Barragan, Fatima; Piltonen, Terhi T.; Chen, Joseph C.; Balayan, Shaina; Irwin, Juan C.; Giudice, Linda C.

In: Biology of Reproduction, Vol. 97, No. 3, 01.01.2017, p. 387-399.

Research output: Contribution to journalArticle

Erikson, David ; Barragan, Fatima ; Piltonen, Terhi T. ; Chen, Joseph C. ; Balayan, Shaina ; Irwin, Juan C. ; Giudice, Linda C. / Stromal fibroblasts from perimenopausal endometrium exhibit a different transcriptome than those from the premenopausal endometrium. In: Biology of Reproduction. 2017 ; Vol. 97, No. 3. pp. 387-399.
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