Molecular and ultrastructure studies on cumulus ovarian cells in cases of unexplained infertility undergoing intracytoplasmic sperm injection (ICSI) treatment | ||||
Biological and Biomedical Journal | ||||
Volume 3, Issue 2, July 2025, Page 145-160 PDF (1.57 MB) | ||||
Document Type: Original Article | ||||
DOI: 10.21608/BBJ.2025.323829.1018 | ||||
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Authors | ||||
Azza A. Attia* 1; Ahmed E. Abdelkareem1; Ahmed F. Galal2; Ahmed Etman3; Reda ElMazoudy1; Nada Fawzy1 | ||||
1Zoology Department, Faculty of Science, Alexandria University, Egypt. | ||||
2Obstetrics and Gynaecology Department, Faculty of Medicine, Alexandria University, Egypt. | ||||
3Clinical Embryology, REPRO FERTILITY CENTER, Alexandria, Egypt. | ||||
Abstract | ||||
Unexplained infertility cases pose a puzzling concern of in vitro fertilization (IVF) protocols. The related mechanisms and signalling pathways of the microenvironment surrounding the cumulus-oocyte complex remain unclear. Herein, the current study is conducted to elucidate the causes of these cases. Patients undergoing unexplained infertility during intracytoplasmic sperm injection (ICSI) and donor females with proven fertility were included in this study. Cumulus cells (CCs) were aspirated and isolated, and the corresponding follicular fluid (FF) was collected. A significant increase was found in malondialdehyde (MDA), caspase-3, and tumor necrosis factor-α (TNF-α) concentrations in CCs of all infertile patients compared to the controls, but no significant changes were noticed in calcium ion concentrations. A marked DNA fragmentation pattern was observed, along with a significant increase in the calculated DNA length, in the patients' cumulus cells. Additionally, a significant decrease in reduced glutathione (GSH) levels was detected in the follicular fluid (FF) of all infertile patients compared to the controls. A significant increase in the concnetration of phosphatase and tensin homolog (PTEN). Zinc ion concentration was significantly increased in patients. Ultrastructurally, distinct alterations in the nuclei, loss of microvilli, hypertrophied Golgi bodies, abnormal mitochondria, large autophagic vacuoles, and increased smooth endoplasmic reticulum were evident in CCs of patients. Under molecular and biochemical levels, the intricacy of componentry of microenvironment, like caspase-3, TNF-α, PTEN and DNA damage, MDA, GSH, may likely play a crucial role in creating defective conditions for unexplained infertility and may be linked to oocytes' failure to complete maturation and subsequent competency. These were also evident by ultrastructural alterations of CCs. Understanding this complexity could be key to unlocking solutions for those facing challenges in conception. we suggest that PTEN in the FF represents a valuable diagnostic biomarker for unexplained infertility. Further investigation under a large-scale cohort is required to prove the validity of these findings and to explore possible implementation in unexpected infertility. | ||||
Keywords | ||||
Cumulus cells; Electron microscope; Follicular fluid; In vitro fertilization; PTEN; Tumor necrosis factor; Unexplained infertility | ||||
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