Dynamic Transcriptomic Profiling of Mouse Endometrium Across the Estrous Cycle Reveals Phase-Specific Regulatory...

Area of Science:

• Reproductive Biology
• Genomics
• Molecular Endocrinology

Background:

• The mouse estrous cycle involves cyclical endometrial remodeling crucial for uterine function and embryo implantation.
• The precise molecular mechanisms governing these dynamic endometrial changes are not fully understood.

Purpose of the Study:

• To comprehensively map the transcriptomic landscape of the mouse endometrium across the four estrous cycle phases.
• To identify key molecular regulators and pathways orchestrating endometrial regeneration and preparation for implantation.

Main Methods:

• Vaginal smear cytology for estrous staging and histological assessment of endometrial morphology.
• Comprehensive RNA sequencing of endometrial tissue across proestrus, estrus, metestrus, and diestrus.
• Integration of Weighted Gene Co-expression Network Analysis (WGCNA), MFUZZ, and differential gene expression analysis (DESeq2).

Main Results:

• Identified phase-specific gene expression signatures related to cell cycle, extracellular matrix organization, oxidative phosphorylation, and DNA replication.
• Discovered high-connectivity hub genes and pathways, including Natural Killer (NK) cell-mediated cytotoxicity, Estrogen signaling, and Wnt signaling.
• Pinpointed transcription factors (Sox4, Lef1) and cell cycle regulators (Cks1b) with expression patterns linked to endometrial proliferation.

Conclusions:

• Delineated a complex hub-gene regulatory network governing cyclic endometrial regeneration in mice.
• Provided a comprehensive transcriptomic atlas of the murine endometrium.
• Offered novel insights into uterine biology relevant to reproductive health and disease.