Decidualization of Human Endometrial Stromal Fibroblasts is a Multiphasic Process Involving Distinct Transcriptional...

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Genomics

Background:

• Decidual stromal cells are vital for pregnancy, originating from endometrial stromal fibroblasts (ESFs) under hormonal influence.
• Their evolution coincides with the development of implantation in placental mammals.

Purpose of the Study:

• To compare early (3-day) and late (8-day) gene transcription patterns during in vitro decidualization of human ESFs.
• To elucidate the dynamic molecular changes and regulatory pathways involved in decidualization.

Main Methods:

• Utilized a well-established in vitro decidualization protocol.
• Analyzed gene transcription patterns (transcriptomes) at early and late time points (3 and 8 days) in immortalized human ESFs.
• Investigated the impact of progesterone withdrawal on cell proliferation and death.

Main Results:

• Observed extensive and dynamic changes in the decidual cell transcriptome over time.
• Identified an early phase dominated by signal transducer and activator of transcription (STAT) pathways and a later phase regulated by nuclear factor κB (NFKB) pathways.
• Confirmed that both phases are under progesterone receptor (PGR) control, with decidualization inducing proliferative quiescence that is reversible by progesterone withdrawal, though less so after prolonged exposure.

Conclusions:

• Decidualization exhibits a biphasic gene expression dynamic, transitioning between STAT and NFKB pathway dominance.
• These distinct phases likely reflect sequential events in establishing the critical fetal-maternal interface for successful pregnancy.
• Progesterone withdrawal induces cell death, highlighting the hormone's role in decidual cell survival.