A major Japanese study found that KNDy neurons are critical for controlling ovarian function in mammals. It can be a path towards creating infertility remedies.
Gonadotropins are all hormones released by the anterior pituitary gland to stimulate the gonads, or sexual glands, to perform their reproductive functions.
Gonadotropin-releasing hormone (GnRH) is critical for mammalian reproduction.
In a healthy reproductive system, GnRH is produced by the brain. Statistics suggest that at least 25% of ovarian disorders it is due to the dysfunction of the brain mechanism that controls the release of gonadotropins. A type of reproductive disorder associated with the hypothalamus.
The source of the GnRH pulse generator has been a mystery for decades to this day.
In February 2020 a first study (on other components) opened a glimpse into new working methods. Now there is more clarity.
now a new search conducted by a Japanese collaboration between Nagoya University and the Okazaki National Institute of Physiological Sciences, published in the Proceedings of the National Academy of Sciences, changes the game.
The study provides the first direct evidence that KNDy neurons generate GnRH discharges, and the lack of these inhibits fertility.
In experiments on mice, the study also showed that saving just 20% of KNDy neurons is enough to restart GnRH and gonadotropin pulses, and restore fertility.
Pulsatile release of GnRH into the pituitary portal vein from the hypothalamus is critically important for gonadal function in mammalian species, including humans.
Hiroko Tsukamura, professor at Nagoya University and author of the paper.
KNDy neurons and gonadotropins: two words
The acronym KNDy comes from peptides (signaling molecules) kisspeptin, neurokinin-B (NKB) and dynorphine-A released from this part of the hypothalamus
For this reason, kisspeptin arcuate neurons are also known as KNDy neurons.
The research team used an animal model with congenital infertility, in which the kisspeptin (Kiss1) gene had been genetically deleted. He then saved the KNDy neurons transfecting the Kiss1 gene in the rat brain using a viral vector that carries the gene.
The team noted that saving only 20% of KNDy neurons resulted in the release of pituitary gonadotropins, with concomitant growth of ovarian follicles to pre-ovulatory size.
Gonadotropins and KNDy neurons: confirmation
The results of the experiment were confirmed in the second phase of the research by reversing the process in the first phase. The elimination of more than 90% of the Kiss1 gene resulted complete suppression of the pulsed release of gonadotropins.
Taken together, these results provide the first direct evidence that KNDy neurons are the GnRH pulse generator and that saving only 20% of KNDy neurons is sufficient to restart GnRH and gonadotropin pulses and to maintain ovarian follicle growth. , thus recovering fertility.
The discovery provides a potential therapeutic approach for patients with reproductive disorders. A “universal” methodology for all mammalian species, including cattle, sheep, goats and pigs, primates and experimental rodent models, which have the same brain mechanism to regulate reproductive function.
The team thinks there is still a lot of work to be done to find the exact molecular mechanism that controls KNDy neuronal activity and leads it to produce gonadotropins.
However, they say, the present findings help to elucidate the central mechanism behind mammalian reproduction.
