SARS-CoV-2 Hijacks Steroidogenesis and Lipid Metabolism in Male Reproductive Cells to Fuel Its Replication!
Nikhil Prasad Fact checked by:Thailand Medical News Team Apr 25, 2025 6 hours, 36 minutes ago
Medical News: A new scientific investigation has shed light on why men tend to suffer more severe outcomes from COVID-19 compared to women. An international team of researchers from the Federal University of São Paulo, the School of Medicine at the University of Virginia, the University of Ribeirão Preto, and São Paulo State University has discovered that SARS-CoV-2 directly infects testosterone-producing cells in the male reproductive system and manipulates their biological processes to boost its own survival and replication.
SARS-CoV-2 Hijacks Steroidogenesis and Lipid Metabolism in Male Reproductive Cells to Fuel Its Replication
COVID-19’s Hidden Impact on Male Hormonal Health
The research team studied Leydig cells—cells located in the testes that are primarily responsible for producing testosterone. Using K18-hACE2 mice, which are genetically modified to express human ACE2 receptors (the same ones the virus uses to enter human cells), the scientists observed how SARS-CoV-2 infiltrates these vital cells and rewires them for its own benefit.
This
Medical News report highlights that Leydig cells in the infected mice showed increased presence of human ACE2, along with viral proteins including the spike and nucleocapsid proteins. The virus also triggered the immune sensor RIG-I and led to elevated levels of pro-inflammatory markers like TNF-α, IL-1β, and IL-6. The result was a significant decline in testosterone levels and steroidogenic proteins such as SF1.
What Is Steroidogenesis and Why Does It Matter?
Steroidogenesis is the process by which steroid hormones, such as testosterone, are synthesized from cholesterol through a series of complex, enzyme-driven steps. This critical biological process takes place in specialized cells in the adrenal glands and gonads (including the Leydig cells in the testes). Disruption of steroidogenesis can result in hormonal imbalances that affect fertility, metabolism, mood, and immune function.
The Virus Exploits Fat and Hormone Pathways
Beyond disrupting hormone production, SARS-CoV-2 was shown to hijack the lipid metabolism pathways in Leydig cells. The study identified increased expression of genes such as Dgat1, Srebp, and Scarb1, all of which are involved in fat synthesis and regulation. Under electron microscopy, the Leydig cells were filled with lipid droplets, and viral particles were found hiding inside them. This suggests that the virus may use these fat stores as energy sources and as shelter to evade the immune system while replicating.
Local Inflammation Adds to the Damage
Researchers also observed an increase in testicular macrophages and the immune modulator MIF (macrophage inhibitory factor), which indicates that the infection triggers a local immune response that could further impair the functionality of these reproductive cells. Inflammatory damage in this region may lead to longer-term reproductive issues, even af
ter the virus has been cleared from the body.
Why This Matters for Men with COVID-19
The findings from this study support clinical observations that men with severe COVID-19 often have significantly reduced levels of testosterone and high-density lipoprotein (HDL), a key component of healthy cholesterol balance. The study provides biological evidence that SARS-CoV-2 not only infects but also manipulates steroidogenesis and lipid metabolic processes in Leydig cells to facilitate its own replication. This may help explain the higher mortality and complication rates seen in male COVID-19 patients.
Final Thoughts
These findings are a critical step toward understanding how SARS-CoV-2 affects the male reproductive system at a cellular level. The virus’s ability to hijack both hormone-producing and fat-processing mechanisms in Leydig cells highlights a dual-threat strategy that may lead to long-term hormonal and fertility problems. Addressing these consequences may become a new priority in the post-COVID-19 era of men’s health.
The study findings were published as an abstract in the peer reviewed journal: Frontiers in Cellular and Infection Microbiology.
https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1538461/abstract
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