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

## TL;DR

This study finds that women with recent COVID-19 infection show changes in genes related to inflammation, blood vessels, and cell cycles in their reproductive cells, which could affect fertility.

## Contribution

The study is the first to report gene expression changes in granulosa cells of women with recent SARS-CoV-2 infection undergoing ART.

## Key findings

- Inflammatory cytokines IL-1B, TNF-α, IL-6, and IL-8 were significantly upregulated in granulosa cells of women with recent COVID-19.
- Vascular genes VEGF and ANGPT1 were overexpressed, while FOXL2 was downregulated and Cyclin D1/D2 were upregulated in infected women.
- LH and FSH receptor expression remained unchanged between the groups.

## Abstract

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.