Hormone 'pulses' that govern fertility are regulated by brain cells

A specific type of neuron is essential to fertility, Japanese researchers have discovered, suggesting a possible new approach to combat infertility. 

The cells, called KNDy neurons, which are found in the hypothalamus brain region, were shown to be required in generating the 'pulses' of hormones that drive the reproductive systems of male and female mammals. The mechanism by which these pulses are generated had previously been a mystery.

'Reports suggest that at least 25 percent of ovarian disorders are due to dysfunction of the brain mechanism controlling the release of gonadotropins, a kind of hypothalamic reproductive disorder,' said Professor Hiroko Tsukamura, from Nagoya University, who led the research.

Gonadotropin-releasing hormone (GnRH) is a molecule controlled by the hypothalamus that regulates the release of a range of reproductive hormones – such as gonadotropins – into the bloodstream. 

KNDy neurons are known to secrete several signalling molecules including kisspeptin, a hormone encoded by the Kiss1 gene, that is linked to puberty onset and influences the development of ovaries and testes. Additionally, kisspeptin signalling plays a key role in regulating the healthy release of GnRH (that is, in pulses) and subsequent release of gonadotropin pulses. 

The study, published in Proceedings of the National Academy of Sciences, used genetically modified female rats to demonstrate that a lack of properly functioning KNDy neurons causes infertility. Researchers deleted the Kiss1 gene in a female rat to stop kisspeptin production and observed that no GnRH/gonadotropin pulses were produced and that the animal was infertile. On the contrary, when they boosted the number of properly functioning KNDy neurons by inserting the Kiss1 gene, gonadotropin pulses started again. 

'KNDy neuron deficient male and female mammals can never be fertile,' said Professor Tsukamura 'Seen in this light, KNDy and then gonadotropin-releasing hormone neurons are indispensable for fertility in both male and female mammals'.

The authors suggest that 'rescuing' KNDy neurons using gene therapy could prove effective in restoring fertility. They plan to conduct further studies to translate these findings into humans.