Molecular and ultrastructure studies on cumulus ovarian cells in cases of unexplained infertility undergoing intracytoplasmic sperm injection (ICSI) treatment

Attia, Azza A.; Abdelkareem, Ahmed E.; Galal, Ahmed F.; Etman, Ahmed; ElMazoudy, Reda; Fawzy, Nada

doi:10.21608/BBJ.2025.323829.1018

Molecular and ultrastructure studies on cumulus ovarian cells in cases of unexplained infertility undergoing intracytoplasmic sperm injection (ICSI) treatment

Document Type : Original Article

Authors

¹ Zoology Department, Faculty of Science, Alexandria University, Egypt.

² Obstetrics and Gynaecology Department, Faculty of Medicine, Alexandria University, Egypt.

³ Clinical Embryology, REPRO FERTILITY CENTER, Alexandria, Egypt.

10.21608/BBJ.2025.323829.1018

Abstract

Unexplained infertility remains a significant barrier in assisted reproductive technologies, particularly in in vitro fertilization (IVF). The contribution of the cumulus–oocyte complex microenvironment to this condition is still poorly defined. This study aimed to characterize molecular, biochemical, and ultrastructural alterations in cumulus cells (CCs) and follicular fluid (FF) associated with unexplained infertility. Women with unexplained infertility undergoing intracytoplasmic sperm injection (ICSI) and fertile donor controls were recruited. CCs were isolated, and corresponding FF samples were collected. Biochemical analyses included malondialdehyde (MDA), caspase-3, tumor necrosis factor-α (TNF-α), reduced glutathione (GSH), calcium, zinc ions, phosphatase, and tensin homolog (PTEN). DNA fragmentation was evaluated, and CC ultrastructure was examined by transmission electron microscopy. Compared with fertile controls, infertile patients exhibited significantly elevated levels of MDA, caspase-3, TNF-α, PTEN, and zinc ions, while calcium ion concentrations remained unchanged. FF showed a significant reduction in GSH. CCs from infertile patients demonstrated pronounced DNA fragmentation and ultrastructural abnormalities, including nuclear deformation, loss of microvilli, hypertrophied Golgi bodies, mitochondrial disruption, autophagic vacuoles, and expansion of smooth endoplasmic reticulum. The interplay of oxidative stress, apoptotic signaling, PTEN dysregulation, and ultrastructural damage in CCs appears to compromise oocyte maturation and competence, thereby contributing to unexplained infertility. Elevated PTEN in FF may represent a novel biomarker with potential diagnostic value, warranting validation in larger cohorts.

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