Restoring the function of KNDy neurons in the brain can overcome infertility

A recent Japanese study has shown that restoring the function of a particular type of cells in the brain, called KNDy neurons, can help reverse certain forms of infertility, including anovulation and hypothalamic dysfunction.

The gonadotropin-releasing hormone and its role in fertility

The gonadotropin-releasing hormone (GnRH =Gonadotropin Releasing Hormone) is secreted by cells in the hypothalamus, where it triggers a cascade of intracellular signaling. GnRH stimulates the synthesis and release of the gonadotropins FSH and LH at the adenohypophysis level, which in turn stimulate the synthesis of sex hormones in the ovaries and testes. Thus, GnRH plays a key role in normal sexual development and reproductive function in both men and women.

“Reports show that at least 25% of ovarian disorders are due to hypothalamic dysfunction, which controls the release of gonadotropins,” notes Hiroko Tsukamura, a professor at Nagoya University in Japan.

KNDy neurons: the operating mechanism

Tsukamura and her colleagues confirmed that KNDy neurons control the release of the gonadotropin-releasing hormone (GnRH). These neurons interact with other hypothalamic structures by secreting three molecules: kisspeptin, neurokinin B, and dynorphin. Together, they form a complex network that regulates the rhythmic release of hormones, thereby synchronizing endocrine processes. Kisspeptin, in particular, plays a central role in stimulating GnRH production, allowing for normal sexual development.

Study on genetically modified rats

To test this hypothesis, scientists created genetically modified female rats with extremely low levels of kisspeptin. These rats exhibited abnormal levels of gonadotropin-releasing hormone and were consequently sterile. This experiment confirmed the importance of KNDy neurons and kisspeptin in regulating reproductive function.

Gene therapy: a step towards healing

Scientists developed a gene therapy to restore the function of KNDy neurons. The method involves using a viral vector to introduce a gene coding for kisspeptin into specific hypothalamic cells. Once the gene was introduced, the neurons began to produce kisspeptin, which contributed to a partial restoration of their functionality. Although only about 20% of KNDy neurons became active after the gene therapy, it normalized GnRH levels and restored ovarian function in experimental rats.

Limitations and perspectives of the method

The research team plans to conduct further experiments on larger animals to better understand the mechanism of action of the method and assess its safety. The limitations of the method are the low percentage of restored functional neurons and the need for long-term observation of the effects of gene therapy. However, scientists believe that within the next 5 to 10 years, this technology could be adapted and used in human reproductive medicine.

The discovery of the role of KNDy neurons and gene therapy in the treatment of infertility represents an important step in the development of reproductive medicine. Despite current limitations, this technology has great potential to help patients suffering from disorders related to the secretion of gonadotropin-releasing hormone. In the future, it could open new horizons for the treatment of infertility in humans.

For more information on in vitro fertilization (IVF), see the section on treatments.