Expression of pro-apoptotic and anti-apoptotic proteins in granulosa cells of women with diminished ovarian reserve.

Purpose: To evaluate the expressions of caspase-3 and cytochrome c and heat shock protein 70 (Hsp70) in granulosa cells (GCs) from women with normal ovarian reserve (NOR) and diminished ovarian reserve (DOR) undergoing intracytoplasmic sperm injection (ICSI).

Methods: GCs were collected from 117 infertile women during oocyte retrieval. Patients were classified into four groups as follows: DOR-COC score of 0, DOR-COC score of I, NOR-COC score of 0, and NOR-COC score of I. The caspase-3, cytochrome c, and Hsp70 analyses were performed immunohistochemically in GCs. The ICSI outcomes were evaluated prospectively.

Results: The clinical pregnancy and live birth rates were higher in DOR-COC score of I (15, 30.6%; 14, 38.9%) and NOR-COC score of I (19, 38.77%; 19, 52.7%) groups, compared with DOR-COC score of 0 (12, 24.4%; 3, 6.1%) and NOR-COC score of 0 (3, 6.1%; 0%) groups (p = 0.0001; 0.00002), respectively. Caspase-3 and cytochrome c expression levels were higher in DOR-COC score of 0 (23, 65.7%; 25, 71.4%) and NOR-COC score of 0 groups (19, 61.3%; 20, 64.5%), compared with DOR-COC score of I (8, 32%; 9, 36%) and NOR-COC score of I groups (7, 26.9%; 8, 30.8%) (p = 0.00297; p = 0.002), respectively. Lower expression levels of Hsp70 were found in DOR-COC score of 0 (11, 31.4%) and NOR-COC score of 0 groups (10, 32.3%), compared with DOR-COC score of I (16, 64%) and NOR-COC score of I groups (20, 76.9%) (p = 0.001), respectively. Hsp70 expression levels were positively correlated with the number of day 3 good-quality embryo and negatively correlated with estradiol levels in the DOR group.

Conclusion: Our data suggest that COC score of 0 is associated with increased expression levels of apoptotic proteins, decreased expression levels of anti-apoptotic protein, and poor ICSI clinical outcomes in women with and without DOR.