The relationship between different granulosa cell morphologies and apoptosis in women with PCOS: Impact on clinical outcomes

Abstract

Objective: The microenvironment of the oocyte is composed of granulosa cells (GC), which play a vital role in the process of oogenesis. During Assisted Reproductive Technology (ART) treatment, the morphological characteristics of GC are evaluated. However, this evaluation does not provide definitive clarity. There is a limited amount of research on the underlying mechanisms of abnormal GC morphology, and it remains incompletely understood. Therefore, the aim of our study was to investigate apoptosis in GCs with varied morphologies in patients with different infertility etiologies undergoing intracytoplasmic sperm injection (ICSI). We performed an immunohistochemical analysis of caspase-3, cytochrome c, and heat shock protein-70 (HSP-70) expression levels, and evaluated their impact on assisted reproduction. Patients and Methods: The study comprised 142 patients, including 65 with polycystic ovary syndrome (PCOS) and 77 with male factor (MF) infertility. The granulosa-oocyte complex was analyzed under a stereomicroscope and classified into dark granulosa cells (DGC) and light granulosa cells (LGC). Fertilization rates, embryonic development, and pregnancy outcomes following ICSI were evaluated. DGC exhibited reduced fertilization and pregnancy rates. Results: Caspase-3 and cytochrome c expression levels were significantly elevated in the PCOS DGC (26, 86.6%; 25, 83.3%) and MF DGC (34, 77.2%; 32, 72.7%) groups compared to the PCOS LGC (8, 22.8%; 5, 14.2%) and MF LGC (4, 12.1%; 7, 21.2%) groups (p = 0.001; p = 0.001), respectively. In contrast, expression levels of HSP-70 were significantly lower in the PCOS DGC (6, 20%) and MF DGC (7, 15.9%) groups compared to the PCOS LGC (31, 88.5%) and MF LGC (32, 96.9%) groups (p = 0.001). Conclusion: In the PCOS group, the number of good quality embryos on day 3 exhibited a positive correlation with HSP-70 expression levels and a negative correlation with cytochrome c expression levels. Our findings suggest that DGC morphology is a reflection of apoptosis, which impacts oocyte quality and, consequently, embryonic development, with PCOS contributing to the worsening of this condition.

Keywords

• Granulosa cell
• PCOS
• Apoptosis
• In vitro fertilization
• Embryo development

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