Gene expression pattern of Kisspeptin and RFamide-related peptide (Rfrp) in the male Damaraland mole-rat hypothalamus

Abstract

Damaraland mole-rats (Fukomys damarensis) are cooperatively breeding, subterranean mammals, which exhibit high reproductive skew. Reproduction is monopolized by the dominant female of the group, while subordinates are anovulatory. Similarly, male subordinates within the colony show no sexual behaviour although they have functional gonads and do not differ from reproductive males in circulating levels of pituitary hormones and testosterone. However, reproductive status affects the neuroendocrine phenotype of males with breeders possessing increased mRNA expression of androgen and progesterone receptors compared to non-breeders in several forebrain regions implicated in the regulation of reproductive behaviour. The RFamide peptides kisspeptin and RFRP-3, encoded by the Kiss1 and Rfrp gene, are considered potent regulators of gonadotropin release. In females, reproductive inhibition is associated with reduced Kiss1 expression within the arcuate nucleus (ARC) and increased Rfrp expression in the anterior hypothalamus. To assess whether differential gene expression of Kiss1 and Rfrp underlies the difference in reproductive behaviour of males, we studied the expression of both genes by means of in situ hybridisation in wild-caught male Damaraland mole-rats with different reproductive status. The distribution of Kiss1 and Rfrp within the hypothalamus was found to be similar to females. Quantification of the Kiss1 hybridisation signal revealed no significant differences in relation to reproductive status. However, there was a significant positive correlation between testis mass and the number of Kiss1-expressing cells in the ARC and the mRNA content per cell, respectively. Analysis of the Rfrp hybridisation signal along the rostro-caudal extent of the hypothalamus revealed that non-reproductive males possessed an increased number of Rfrp-expressing cells at the level of the dorsomedial hypothalamic nucleus (DMH) than reproductive males. These data suggest the Kiss1 expression within the ARC is not associated with reproductive quiescence in subordinate males but instead, inhibitory effects may be mediated by Rfrp-expressing cells in the DMH.