Khaberni - Researchers have uncovered a complex biological process that protects germ cells, the precursor cells to sperm, from genetic threats during their early developmental stages, in a manner similar to the immune system.
The study explains how this mechanism prevents "genetic chaos" and maintains the health of the genome to ensure the production of healthy sperm.
The challenge begins long before the sperm reaches the egg, as germ cells in embryos are extremely sensitive. These cells need to protect their DNA during fetal growth to later become regenerative cells that produce healthy sperm throughout adult life.
The discovered mechanism resembles the immune system: it scans the genome and stops known aberrant genes called "jumping genes", while maintaining the integrity of essential genes. This process provides germ cells with what can be called "genetic immortality", i.e., their ability to survive early death and transmit genetic information from parents to offspring.
How do germ cells protect themselves?
During their development, germ cells undergo a reprogramming process that makes them susceptible to jumping genes, which can cause DNA damage and infertility.
Professor Donald O'Carroll, the lead author of the study, explains: "Our immune system protects us from external threats, while germ cells face an internal threat from their own genes. Jumping genes can move across the genome and control gene usage, but their activity must be precisely regulated to avoid damage. If left unchecked, they could cause genetic chaos and destroy the cells."
Researchers at the University of Edinburgh studied the development of germ cells in mouse embryos and found that two genes, SPOCD1 and C19orf84, attract protective chemical markers known as "DNA methylation" to disable jumping genes during reprogramming, a phase that makes cells highly sensitive to damage, making this mechanism a primary line of defense.
A vulnerability in the genome
The study revealed a "blind spot" in the genome: the defense mechanism only reaches certain accessible parts, while other areas remain naturally protected, which may allow jumping genes to hide in them.
The researcher Tamoghna Chowdhury, the main author, clarifies: "Proteins SPOCD1 and TPR (a protein found within germ cells) work together as a checkpoint that prevents jumping genes from hiding in these regions, while maintaining the integrity of the rest of the genome. This mechanism is similar to the way the immune system works, which attacks threats without harming healthy cells."
Effects of the discovery on male infertility
The results indicate that any malfunction in the germ cell protection mechanism, even if it leads to the failure to control just one jumping gene out of hundreds that are active, may cause severe damage to the cells. This damage could potentially be a cause for some forms of unexplained male infertility.
Previous research has shown that rare mutations in the gene SPOCD1 and other genes in this pathway could explain some rare cases of severe forms of infertility. About 1% of men suffer from conditions of low sperm count or azoospermia, i.e., producing very few or no sperm at all.
