Core Binding Factor-β Knockdown Alters Ovarian Gene Expression and Function in the Mouse.

Area of Science:

• Reproductive biology and endocrinology
• Molecular genetics and epigenetics
• Cellular and developmental biology

Background:

• Core binding factor (CBF) is a transcription factor complex essential for gene regulation.
• CBFβ subunit is critical for the DNA binding and stability of the CBF complex.
• CBF expression in the ovary suggests a role in ovulation.

Purpose of the Study:

• To investigate the functional role of CBF complexes (RUNX1/CBFβ and RUNX2/CBFβ) in ovarian function.
• To examine the ovarian phenotype of granulosa cell-specific CBFβ knockdown mice.
• To identify genes regulated by CBFβ in the ovary.

Main Methods:

• Generated granulosa cell-specific CBFβ knockdown mice (Cbfb f/f * Cyp19 cre).
• Assessed fertility parameters, including litter size and progesterone levels.
• Utilized RNA sequencing to analyze gene expression changes in granulosa cells post-hCG stimulation.
• Examined ovarian morphology and corpora lutea gene expression.

Main Results:

• CBFβ knockdown mice exhibited significantly reduced fertility, smaller litter sizes, and decreased gestational progesterone.
• Superovulation yielded fewer cumulus oocyte complexes in mutant mice.
• RNA sequencing revealed altered expression of over 200 mRNA transcripts, including key ovulation regulators.
• Morphological changes and decreased luteal gene expression were observed in knockdown ovaries.

Conclusions:

• CBFβ plays a critical role in regulating gene expression, ovulatory processes, and luteal development in the ovary.
• Disruption of CBFβ impacts female fertility and ovarian structure.
• CBF complexes are significant regulators of ovarian function and require further investigation.