HDAC3 Regulates Transcriptional Networks Governing Decidualization.

Area of Science:

• Reproductive Biology
• Epigenetics
• Genomics

Background:

• Decidualization is vital for pregnancy, involving fibroblast transformation into decidual cells.
• Epigenetic regulators, like histone modifications, are critical for uterine receptivity and decidualization.
• Previous work showed histone deacetylase 3 (HDAC3) loss impairs decidualization and causes infertility.

Purpose of the Study:

• To investigate the genome-wide transcriptomic changes in HDAC3-deficient uteri.
• To elucidate the molecular mechanisms underlying impaired decidualization due to HDAC3 loss.

Main Methods:

• Uterine-specific Hdac3 knockout mice (Pgr^cre/+Hdac3^f/f; Hdac3^d/d) were used.
• Artificial decidualization was induced for 3 days.
• RNA sequencing analyzed transcriptomic alterations in control versus Hdac3-deficient uteri.

Main Results:

• Hdac3 deficiency led to decidual defects and widespread gene/pathway dysregulation.
• Key pathways altered included RHOA, AMPK-NOTCH1-HEY1, and oxidative stress signaling.
• Expression of Limk1, Prkag1, and Cbx2 was significantly reduced in Hdac3-deficient uteri.

Conclusions:

• HDAC3 is a critical regulator of the transcriptional and signaling networks essential for decidualization.
• HDAC3 deficiency disrupts cytoskeletal remodeling, cellular metabolism, and oxidative stress responses.
• This study provides a transcriptomic profile of HDAC3-deficient uteri, advancing understanding of pregnancy establishment.