ATR function is indispensable to allow proper mammalian follicle development.

Area of Science:

• Reproductive Biology
• Cellular Biology
• Genetics

Background:

• Mammalian female fertility depends on ovarian follicle development.
• Oocytes and somatic cells form follicles post-birth, which mature to produce gametes.
• The ATM and rad3-related (ATR) kinase plays a role in DNA repair and cell cycle regulation.

Purpose of the Study:

• To investigate the role of the ATR kinase in mouse oogenesis and folliculogenesis.
• To determine if reduced ATR levels affect meiotic recombination or follicle development.
• To understand the cause of sterility in mice with a hypomorphic Atr mutation.

Main Methods:

• Utilized a hypomorphic mutation of the Atr gene in mice.
• Analyzed oocyte meiotic prophase progression.
• Assessed follicle development, cell death, and proliferation in Atr mutant ovaries.

Main Results:

• Reduced ATR levels did not grossly alter female meiotic prophase.
• Follicle development was significantly compromised in Atr mutant ovaries.
• A decrease in growing follicles and altered cell proliferation/death were observed.

Conclusions:

• Wild-type ATR levels are essential for optimal follicular development.
• Reduced ATR expression causes female sterility primarily due to defects in follicular progression, not meiotic recombination.
• Findings have implications for ATR inhibitor side-effects on female fertility.