Microscopic view of endometrial cells transforming, representing menopause.

Decoding Menopause: How Endometrial Cells Change with Age

Avery Sinclair in Health & Wellness December 2025 • 4 min read.

"Unlocking the Secrets of Aging Endometrium: A Deep Dive into Stromal Fibroblasts and Transcriptome Shifts During Menopause"

The endometrium, the inner lining of the uterus, undergoes cyclic regeneration in premenopausal women, orchestrated by the hormones estradiol (E2) and progesterone (P4). This intricate process relies on stem and progenitor cells from epithelial, mesenchymal, and endothelial lineages, ensuring the endometrium's renewal with each menstrual cycle. Understanding this dynamic process is critical for women's health.

As women transition into menopause, marked by a decline in ovarian follicles, menstrual cycles cease. This phase, known as perimenopause, is characterized by fluctuating endocrine levels and biological changes, often leading to prolonged estrogen exposure without sufficient progesterone. This hormonal imbalance elevates the risk of endometrial disorders, including polyps, hyperplasia, and cancer. A deeper understanding of cellular changes during this transition is essential.

Recent research has identified mesenchymal stem cells (eMSC) within the endometrium, co-expressing markers such as CD146 and PDGFRB. These eMSCs can differentiate into endometrial stromal fibroblasts (eSF), playing a vital role in tissue regeneration. Investigating how these cell populations evolve during perimenopause can offer insights into maintaining endometrial functionality and preventing related disorders as women age.

What Happens to Endometrial Cells During the Menopause Transition?

Microscopic view of endometrial cells transforming, representing menopause.

A recent study by Erikson et al. investigated the gene expression profiles of eMSC and eSF cells in perimenopausal women compared to premenopausal women. Endometrial tissue samples were collected from both groups, and microarray analysis was performed on FACS-isolated eSF and eMSC cells. The goal was to understand how these cell populations change during the menopausal transition.

The researchers used principal component analysis (PCA) and hierarchical clustering (HC) to analyze the data. These statistical methods allowed them to group cells with similar gene expression patterns. The results revealed distinct clustering patterns:

Perimenopausal and Premenopausal eMSC Clustered Together: eMSC cells from both groups showed similar transcriptomic signatures.
Perimenopausal and Premenopausal eSF Formed Separate Clusters: eSF cells from perimenopausal women exhibited different gene expression profiles compared to those from premenopausal women.

These findings suggest that while the fundamental characteristics of eMSC remain relatively stable during the menopausal transition, eSF undergo significant changes. Pathway analysis further revealed that perimenopausal eSF exhibit dysregulation of cytoskeleton, proliferation, and survival pathways compared to their premenopausal counterparts.

The Implications for Women's Health

This research highlights that the changing hormonal environment of perimenopause significantly impacts endometrial stromal fibroblasts, leading to altered gene expression and pathway activation. Understanding these changes can provide insights into the aging endometrium and its relevance to reproductive health in older women. Further studies are needed to explore the specific mechanisms driving these changes and their potential implications for endometrial disorders.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

What is the normal function of the endometrium in premenopausal women?

The endometrium, which is the inner lining of the uterus, relies on stem and progenitor cells from epithelial, mesenchymal, and endothelial lineages to regenerate during each menstrual cycle in premenopausal women. This regeneration is orchestrated by the hormones estradiol (E2) and progesterone (P4). These hormones ensure the endometrium's renewal, which is vital for reproductive health. The dynamic process is important because any disruption can lead to endometrial disorders, making the understanding of these cell dynamics critical.

Why does the risk of endometrial disorders increase during perimenopause?

During perimenopause, as ovarian follicles decline, women experience fluctuating endocrine levels, often with prolonged estrogen exposure and insufficient progesterone. This hormonal imbalance elevates the risk of endometrial disorders such as polyps, hyperplasia, and cancer. The balance of hormones such as estradiol (E2) and progesterone (P4) is critical to maintaining a healthy endometrium.

What are endometrial stromal fibroblasts (eSF), and how do they change during the menopausal transition?

Endometrial stromal fibroblasts (eSF) are cells within the endometrium that undergo significant changes during the menopausal transition. Research shows that eSF cells from perimenopausal women exhibit different gene expression profiles compared to those from premenopausal women. These changes include dysregulation of cytoskeleton, proliferation, and survival pathways. These alterations in gene expression and pathway activation can provide insights into the aging endometrium and its relevance to reproductive health in older women.

What role do mesenchymal stem cells (eMSC) play in the endometrium during menopause, and how are they affected?

Mesenchymal stem cells (eMSC), specifically those co-expressing markers such as CD146 and PDGFRB within the endometrium, play a vital role in tissue regeneration. These eMSCs can differentiate into endometrial stromal fibroblasts (eSF). The study indicated that eMSC cells remain relatively stable during the menopausal transition, maintaining similar transcriptomic signatures in both premenopausal and perimenopausal women. This stability is crucial for the ongoing maintenance and potential repair of the endometrial lining despite hormonal changes.

What are principal component analysis (PCA) and hierarchical clustering (HC), and how were they used in the study of endometrial cells?

Principal component analysis (PCA) and hierarchical clustering (HC) are statistical methods used to analyze gene expression data from endometrial cells. PCA helps reduce the dimensionality of complex data sets by identifying principal components that capture the most variance, while HC groups cells with similar gene expression patterns into clusters. These methods allowed researchers to reveal that endometrial stromal fibroblasts (eSF) from perimenopausal women formed separate clusters from those of premenopausal women, indicating significant differences in gene expression profiles. These techniques are essential for making sense of large datasets and identifying meaningful patterns.