The role of kisspeptin in reproductive function in the ewe

Abstract

Summary Kisspeptin is a hypothalamic neuropeptide that is critical for fertility. In virtually all species, kisspeptin neurons stimulate gonadotrophin-releasing hormone (GnRH) secretion and act as transmitters for sex-steroid feedback to GnRH neurons. In sheep, kisspeptin neurons are located in the preoptic area and the arcuate nucleus (ARC), with the latter involved in both oestradiol positive and negative feedback regulation of GnRH. In addition, sheep are seasonal breeders, with an annual cycle controlled by changes in the pulsatile secretion of GnRH. Kisspeptin neurons are also important in this phenomenon showing increased expression and terminal apposition to GnRH neurons during the breeding season. Reduced kisspeptin expression during the non-breeding season can be overcome by administration of kisspeptin, which causes ovulation in seasonally acyclic females. On the other hand, kisspeptin neurons do not appear to express the melatonin receptor, so the transduction of photoperiod to these neurons must be indirect, perhaps involving dopaminergic suppression during the non-breeding season. Importantly, kisspeptin neurons of the ARC do not operate in isolation. Autoregulation of kisspeptin expression by the neuropeptides neurokinin B and dynorphin is a key contributor to the “KNDy neuron” concept and the hypothesis that these neurons comprise the GnRH pulse generator. Indeed, the pheromone-induced interruption of seasonal anestrus, known as the male effect, appears to be mediated by KNDy signalling. However, the ‘KNDy hypothesis’ for GnRH pulse generation is still unproven and, indeed, the precise role of KNDy cells in seasonal breeding has yet to be determined.