Fertility & Brain Immunity: New Link Discovered by Spanish Researcher

Researchers have discovered a surprising link between fertility and immune cells in the brain, potentially opening new avenues for understanding and addressing infertility. A study led by Eva González-Suárez at the Spanish National Cancer Research Centre (CNIO) revealed that microglia – defensive cells of the nervous system – and the protein RANK play a role in the hormonal regulation system governing sexual maturation.

The findings, published in the journal Science, were initially made in animal models but have also identified genetic mutations associated with a rare syndrome linked to infertility in humans. This suggests the connection between brain immunity and reproductive function may extend to people.

How the Brain Influences Fertility

The process of puberty and the development of fertility typically begins in the hypothalamus, a region of the brain. Here, neurons release a hormone that activates the pituitary gland, which then releases other hormones to initiate the maturation of the ovaries or testes. This is known as the hypothalamic-pituitary-gonadal (HPG) axis.

The CNIO research demonstrates that microglia and the protein RANK are also involved in this complex hormonal system. RANK is already known for its role in bone remodeling and the development of mammary glands, but its connection to the brain’s immune system and fertility had not been previously understood.

The Role of RANK and Microglia

According to the study, microglia, the resident immune cells of the brain, interact with RANK to influence the HPG axis. While the exact mechanisms are still being investigated, the researchers believe this interaction modulates the hormonal signals necessary for proper sexual maturation and reproductive function.

The team has unexpectedly discovered that cells from the brain immune system play a role in the sexual maturation process. The link between them is RANK, a protein involved in mammary gland development.

Eva González-Suárez, researcher at the Spanish National Cancer Research Centre

González-Suárez previously discovered the key role of RANK in the development of breast cancer in 2010. This new research builds upon that foundation, revealing a broader function for RANK in regulating physiological processes beyond cancer development.

Implications for Infertility Treatment

The discovery of this brain-fertility connection could have significant implications for the development of new infertility treatments. Currently, most treatments focus on addressing hormonal imbalances or physical obstructions in the reproductive system. This research suggests that targeting the brain’s immune system could offer a novel approach.

The identification of genetic mutations associated with infertility in humans that also affect this brain-immune pathway is particularly promising. It suggests that these mutations may disrupt the normal communication between microglia, RANK, and the HPG axis, leading to reproductive dysfunction.

However, researchers caution that this is still early-stage research. Further studies are needed to fully understand the complex interplay between the brain’s immune system, RANK, and fertility. The research was conducted in animal models, and more work is required to confirm these findings in humans.

The team plans to continue investigating the specific mechanisms by which microglia and RANK influence the HPG axis, as well as exploring potential therapeutic targets for restoring reproductive function in individuals with infertility related to disruptions in this pathway. This research opens a new and exciting field of study in reproductive biology.

The study was led by Eva González-Suárez, head of the CNIO Transformation and Metastasis Group, with Alejandro Collado as the first author and co-corresponding author.