Changes in Inflammatory Cytokines, Vascular Markers, Cell Cycle Regulators, and Gonadotropin Receptors in Granulosa Cells of COVID-19 Infected Women

Background: COVID-19 infection can negatively affect multiple organ systems, including the reproductive system. Previous research has indicated altered levels of inflammatory markers in the reproductive tissues of women with chronic diseases. This study aimed to assess the expression of inflammatory, vascular, cell cycle, and gonadotropin receptor genes in the granulosa cells and oocytes of women with recent COVID-19 infection undergoing Assisted Reproductive Technology (ART), compared to healthy controls. Materials and Methods: The study involved 15 women who had tested positive for COVID-19 within three months of ART treatment and 15 age-matched healthy women as controls. Granulosa cells were collected during oocyte retrieval, and RNA was isolated to analyze gene expression using quantitative real-time PCR. The evaluated genes included inflammatory cytokines (IL-1B, TNF-α, IL-6, IL-8), vascular genes (VEGF, ANGPT1), cell cycle regulators (FOXL2, Cyclin D1, Cyclin D2, KLF4), and gonadotropin receptors (LHCGR, FSHR). Results: Results showed significantly higher expression of inflammatory cytokines in the granulosa cells of COVID-19 positive women, including IL-1B (4.2-fold), TNF-α (3.8-fold), IL-8 (2.5-fold), and IL-6 (3.2-fold). Vascular genes VEGF and ANGPT1 were also overexpressed, while FOXL2 was downregulated and Cyclin D1/D2 were upregulated in the study group. However, LH and FSH receptor expression remained similar between both groups. Conclusion: The present study demonstrates altered gene expression of inflammatory cytokines, vascular factors and cell cycle regulators in granulosa cells and oocytes of COVID-19 positive women undergoing ART. The dysregulated molecular pathways could potentially impair folliculogenesis and oocyte development in SARS-CoV-2 infected individuals.