Mitochondrial Stress Response Gene Clpp Is Not Required for Granulosa Cell Function

Area of Science:

• Cellular Biology
• Reproductive Biology
• Mitochondrial Biology

Background:

• The mitochondrial unfolded protein response (UPR^mt) is a cellular stress response crucial for maintaining mitochondrial homeostasis.
• Caseinolytic peptidase P (CLPP) is a key protease in the UPR^mt pathway, degrading misfolded mitochondrial proteins.
• Global deletion of CLPP in mice leads to female infertility and premature ovarian aging.

Purpose of the Study:

• To investigate the role of CLPP specifically within granulosa and cumulus cells in female reproductive function.
• To determine if granulosa/cumulus cell-specific disruption of the UPR^mt pathway affects fertility and folliculogenesis.

Main Methods:

• Generation of mice with granulosa/cumulus cell-specific deletion of CLPP using a Cre-lox system (Clpp^ΔGC).
• Comparison of reproductive parameters, including fertility, litter size, and folliculogenesis, between Clpp^ΔGC and wild-type (WT) female mice.
• Assessment of oocyte quality by counting germinal vesicle (GV) and MII oocytes.

Main Results:

• Mature Clpp^ΔGC female mice exhibited normal fertility and produced a comparable number of pups per litter to WT mice.
• Folliculogenesis was unaffected, with no significant differences in the numbers of primordial, primary, secondary, early antral, or antral follicles between genotypes.
• The yield of germinal vesicle (GV) and MII oocytes was similar in both Clpp^ΔGC and WT mice.

Conclusions:

• Granulosa/cumulus cell-specific deletion of CLPP does not impair female fertility in mice.
• The UPR^mt pathway mediated by CLPP in granulosa/cumulus cells is not essential for maintaining ovarian follicle development or oocyte quality.
• These findings indicate that CLPP's role in female infertility observed in global knockout models may be due to effects in other tissues or cell types.