Description
Reproduction poses a substantial burden, especially for mammalian females. Puberty onset serves as a vital checkpoint, regulated based on the body’s energy state, to prevent inappropriate reproductive activity under malnutrition. However, the neural basis of this puberty checkpoint remains poorly understood. Here, we demonstrate that peripubertal malnutrition in female mice reduces the synchronous activity episodes of arcuate kisspeptin neurons, which are critical regulators of the gonadotropin axis. Improved dietary availability increased the frequency of this pulsatile activity, facilitating puberty onset. Using a viral-genetic approach, we show that the activity of agouti-related protein neurons in the arcuate nucleus, a hunger center, can bidirectionally regulate the pulsatile activity of kisspeptin neurons and follicular maturation in the ovaries. Collectively, a neural circuit connecting feeding to reproductive centers modulates the frequency of pulsatile kisspeptin neuron activity based on dietary availability, which sheds light on the neural basis of the puberty checkpoint.
Funding information
Grants-in-Aid from the Japan Society for the Promotion of Science (JSPS) to Teppei Goto (Nos. 19K16270, 21K15194, and 24K09651) and Kazunari Miyamichi (Nos. 20K20589 and 21H02587), Mitsubishi foundation and a Takeda Life Science grant to Kazunari Miyamichi, and a RIKEN internal fund to Kazunari Miyamichi. Teppei Goto was also supported by RIKEN Special Postdoctoral Researchers Program.