Khaberni - Spanish researchers have discovered that immune cells in the brain play a crucial role in regulating fertility, alongside a protein previously known for its role in bone health, potentially opening new avenues for the treatment of infertility and puberty disorders,
Puberty begins in a deep area of the brain called the "hypothalamus." There, specific neuronal cells secrete a hormone that activates the pituitary gland at the base of the skull. This gland, in turn, releases other hormones that stimulate the maturation of the ovaries in females or the testes in males. This complex chain is known as the "hypothalamic-pituitary-gonadal axis," and it is responsible for transforming the body into a being capable of reproduction.
A new study from the Spanish National Cancer Research Center (CNIO), published in the journal Science, reveals new "heroes" in this equation previously unknown. The first are "microglia," immune cells that act as a defense and protection system for the nervous system. The second is the RANK protein, already known for its role in bone renewal and mammary gland functions.
The study is led by Dr. Eva Gonzalez-Suarez, who had previously discovered this protein's role in the development of breast cancer in 2010. She confirms that "finding immune cells, not neural, regulating fertility is a very important development."
How does the new mechanism work?
Researchers found that microglia regulate the neuronal cells responsible for fertility through the RANK protein. When the team disabled this protein in test animals, they found:
Animals born without the protein or removed before puberty never reached sexual maturity and suffered a sharp decline in sex hormones.
Mature animals from which the protein was removed became completely infertile within just one month.
The research did not stop at animal experiments but extended to studying human samples from patients suffering from a rare condition called "congenital hypogonadotropic hypogonadism," which causes delayed or absent puberty and infertility. The results were exciting; mutations in the gene responsible for producing the RANK protein were found in some of these patients. This means that the RANK protein could be a promising therapeutic target for fertility disorders and used as a genetic marker to diagnose some cases of unexplained infertility.
Dr. Gonzalez-Suarez points out that the discovery's impact might extend beyond fertility. The presence of immune cells that regulate brain functions in this way opens the door to understanding similar mechanisms in other biological processes, such as regulating appetite and satiety or stress response.
The lead author of the study, Alejandro Quijado, emphasizes the importance of collaboration between different disciplines in achieving this milestone. What began as a question about the role of the RANK protein in breast tissues during puberty led them to consult experts in fertility, neuroscience, and cell biology, resulting in unexpected findings that Quijado describes as "conclusions we would never have reached without this collaboration."
