Selective estradiol sensitivity in 12Z human endometriotic epithelial cell line

Area of Science:

• Cell Biology
• Endocrinology
• Reproductive Biology

Background:

• Estradiol (E2) is a key estrogen regulating physiological and pathophysiological processes.
• Accurate in vitro modeling of estrogen-dependent cellular activities requires cell lines sensitive to E2.
• The 12Z human endometriotic epithelial cell line is a potential model for estrogen-dependent conditions, but its E2 responsiveness is uncharacterized.

Purpose of the Study:

• To characterize the functional responsiveness of the 12Z human endometriotic epithelial cell line to estradiol (E2).
• To investigate the impact of E2 on 12Z cell proliferation, migration, and response in 3D models.
• To explore the molecular mechanisms underlying 12Z cell sensitivity or resistance to E2.

Main Methods:

• Assessed E2 effects on 12Z proliferation and migration (collective and single-cell).
• Evaluated 12Z response to E2 in 3D migration models under physical confinement.
• Overexpressed estrogen receptor alpha (ERα) in 12Z cells to assess functional E2 sensitivity.
• Performed RNA sequencing on E2-treated and control 12Z cells, and on ESR1-overexpressing cells.

Main Results:

• Estradiol (E2) did not significantly affect 12Z cell proliferation, collective migration, or single-cell migration.
• 12Z cells exhibited selective responsiveness to E2 in confined 3D migration models.
• Upregulating ERα in 12Z cells did not enhance their functional E2 sensitivity.
• RNA sequencing revealed differential expression of pseudogenes and non-coding RNAs in response to E2.
• ESR1 overexpression led to downregulation of several signal transduction genes, potentially explaining the lack of E2 sensitivity.

Conclusions:

• The 12Z cell line demonstrates limited functional responsiveness to estradiol (E2) in vitro.
• Estradiol responsiveness in 12Z cells is context-dependent, observed only in confined 3D migration models.
• The molecular underpinnings, including altered gene expression and signal transduction pathways, contribute to the limited E2 sensitivity.
• The utility of the 12Z cell line as a model for estrogen-dependent processes warrants careful consideration due to its predominantly non-responsive phenotype.