Madrid- Researchers of the National Cancer Research Center (CNIO) Spanish researchers have unexpectedly discovered in animal models a link between fertility and immune cells present in the brain and that would participate in the process of sexual maturation.
The research has been done in animal models, but the findings have also led to the detection of mutations associated with a rare infertility syndrome in humans, the CNIO reported; The results of the work have been published today in the Science magazine.
The signal for puberty to begin begins in the brain, specifically in the hypothalamus, where specific neurons release a hormone that activates the pituitary gland, at the base of the skull, which in turn releases other hormones that trigger the maturation of the gonads – the ovaries or testicles.
This mechanism, which culminates in a fertile organism, is the ‘hypothalamic-pituitary-gonadal’ axis, and researchers have now discovered that two hitherto unsuspected elements also participate in this hormonal regulation system: microglia – defensive cells of the nervous system -, and a protein (RANK), which contributes to the remodeling of bones and is essential in the functioning of the mammary glands.
The work has been directed by Eva González-Suárez, head of the Transformation and Metastasis Group at the CNIO, who discovered in 2010 the key role of this protein in the development of breast cancer, and the researcher Alejandro Collado has participated in it.
The ‘hypothalamic-pituitary-gonadal’ axis regulates many processes related to reproduction and the main protagonists in the hypothalamus are neurons that release a type of hormones that control the appearance of pubertythe development of the gonads and the fertility.
It was already known that these neurons are modulated by other neurons, but not that immune cells could influence their functioning; and that is the newly discovered function of microglia, cells that eliminate possible threats and useless molecules in the central nervous system.
“The fact of finding cells that are not neurons, but immune cells, regulating fertility is already important,” said González-Suárez in a press release published by the CNIO.
When the CNIO group suppressed the expression of that protein (RANK) in animal models, reproductive function was distorted in both males and females.; In animals that were born without it, and in those in which the protein was eliminated before puberty, a reduction in sex hormones and loss of functionality of the gonads was observed and these animals did not develop puberty.
When the protein was eliminated in sexually mature specimens, the animals became infertile within a month, stated the CNIO, which stated that to investigate the role of ‘RANK’ in human fertility, the team analyzed samples from patients with ‘congenital hypogonadotropic hypogonadism’, a rare syndrome associated with delayed or absent puberty and infertility.
The results thus show, according to the authors, that this protein (RANK) could be a therapeutic target for endocrine disorders and syndromes that affect fertility, and also a candidate gene for the molecular diagnosis of ‘congenital hypogonadotrophic hypogonadism’.
The authors have valued the importance of interdisciplinary collaboration to reach their discoveries, and have stressed that they have reached conclusions that they could not foresee and have learned about techniques and tools that they can now apply to future studies.