Dietary availability acutely influences puberty onset via a hypothalamic neural circuit

Abstract

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 acts as an adjuster of the frequency of pulsatile kisspeptin neuron activity based on dietary availability, contributing to the neural basis of the puberty checkpoint.

Keywords: agouti-related protein; diet availability; fiber photometry; hypothalamus; kisspeptin; leptin; puberty.