Science reports from CNIO show brain immune cells, microglia, regulate fertility by directly interacting with GnRH neurons via the RANK protein, revealing a non-neuronal influence on puberty and reproduction.

Microglia regulate the hypothalamic-pituitary-gonadal axis by signaling through RANK to modulate GnRH neuron activity, impacting puberty and fertility.

The CNIO team led by Eva González-Suárez published their findings in Science, highlighting the role of microglia in endocrine control and potential new avenues for therapies.

Funding for the research came from the European Research Council, la Caixa Foundation, the Community of Madrid, and Spain’s Ministry of Science, Innovation and Universities.

Support for the study also came from the Ministry of Science, Innovation and Universities via the State Research program and other regional sources.

The study, conducted at CNIO with collaborators, demonstrates interdisciplinary collaboration and points toward new endocrine therapy targets.

CNIO positions itself as Spain’s largest cancer research center, underscoring its scale and impact within European science.

In humans, mutations in the RANK gene have been found in patients with congenital hypogonadotropic hypogonadism, linking RANK signaling to fertility disorders and identifying potential diagnostic and therapeutic targets.

The study integrated animal models with human genetic data from congenital hypogonadotropic hypogonadism patients to identify RANK mutations.

Identified RANK mutations suggest RANK as a candidate gene for diagnosis and a target for therapy in reproductive disorders.

The work showcases interdisciplinary collaboration across Spain, France, and Switzerland, combining neuroscience, endocrinology, and immunology.

The Science paper features first author Alejandro Collado and contributors like Nozha Borjini, Jing Zhai, with inputs from researchers including Manuel Tena-Sempere and Nelly Pitteloud.