p73 Is Required for Ovarian Follicle Development and Regulates a Gene Network Involved in Cell-to-Cell Adhesion

Area of Science:

• Reproductive Biology
• Molecular Biology
• Cell Biology

Background:

• The p73 protein, a member of the p53 family, is expressed in ovarian granulosa cells.
• Its precise role in ovarian folliculogenesis and associated physiological processes remains incompletely understood.

Purpose of the Study:

• To investigate the function of p73 in ovarian follicle development and mammary gland branching.
• To elucidate the molecular mechanisms underlying p73's role in these processes.

Main Methods:

• Utilized p73-deficient mouse models to assess ovarian and mammary gland phenotypes.
• Performed RNA sequencing (RNA-seq) on murine granulosa cells and antral follicles.
• Conducted chromatin immunoprecipitation sequencing (ChIP-seq) to identify p73-regulated genes.

Main Results:

• Loss of p73 resulted in impaired follicle development, ovulation, and corpus luteum formation, leading to reduced progesterone levels.
• p73 deficiency caused defects in mammary gland branching, which were partially rescued by ectopic progesterone.
• RNA-seq identified differentially expressed genes involved in cell adhesion and migration, including components of the focimatrix, in p73-deficient granulosa cells.

Conclusions:

• p73 is essential for ovarian folliculogenesis and plays a critical role in regulating a gene network involved in cell-to-cell adhesion and migration.
• p73's function extends to mammary gland development, with progesterone signaling playing a key role.