Spain's National Cancer Research Centre (CNIO) announced on Mar. 12 that its researchers have identified two new elements involved in the regulation of fertility: microglia, which are immune cells in the nervous system, and the RANK protein. The findings were published in the journal Science and led by Eva González-Suárez, head of CNIO's Transformation and Metastasis Group.
The discovery is significant because it adds to scientific understanding of how puberty and fertility are regulated. Until now, it was known that neurons in the hypothalamus release hormones to activate reproductive organs through what is called the hypothalamic-pituitary-gonadal axis. However, this study shows that immune cells also play a role.
According to the research team, "these results show that RANK could be a therapeutic target for endocrine disorders and syndromes affecting fertility, as well as a candidate gene for the molecular diagnosis of congenital hypogonadotropic hypogonadism." The study found that when RANK expression was suppressed in animal models, both male and female specimens experienced reduced sex hormones and loss of gonad function. Animals without RANK did not undergo puberty or became infertile if RANK was removed after sexual maturity.
The researchers also analyzed genetic samples from patients with congenital hypogonadotropic hypogonadism—a rare syndrome linked to delayed or absent puberty—and found mutations in the gene encoding RANK in some cases. González-Suárez said, "the role of microglia in regulating the function of 'reproductive' neurons is new, and this regulation associated with RANK can occur in other axes, for other functions, such as the appetite-satiety axis, the stress axis, etc."
Alejandro Collado, first author of the article and co-corresponding author from CNIO's group, highlighted interdisciplinary collaboration as key to these findings. "My doctoral thesis started out with the question of whether the RANK protein played any role in the development of mammary tissue... When we realised that we needed to explore issues implying fertility, neurons and brain cells, we started consulting colleagues from other fields," Collado said.
Collado added: "We have reached conclusions that we could not have foreseen and learned techniques and tools that we will now be able to apply to future studies."
