Hormonal and stress-response pathways regulate naked mole rat eusociality. Heterocephalus glaber

Naked mole rats live in eusocial colonies where subordinates help a single dominant female and a few males to breed. We investigated the genome-wide regulatory mechanisms underlying their reproductive division of labor by examining brain and gonad transcriptomes and DNA-methylomes. Subtle expression differences were observed between brains of dominants and subordinates, but differentially expressed genes clustered consistently in a module with similar function for both sexes. Gonadotropin-releasing hormone (GNRH1) was central in this module and linked with stress-response genes such as neuropeptide Y and corticotrophin-releasing hormone. Breeder-subordinate modifications in DNA methylation were substantial in male brains and associated with the GNRH1 module. The GNRH1-regulated estrogen synthesis pathway was completely blocked in subordinate ovaries and sperm-related genes were significantly down-regulated in subordinate testes. Our results indicate that reproductive suppression is based on hormonal- and stress-related control by the dominant female, but with significant differences in molecular mechanisms between males and females. Overall design: Naked mole rats were housed in our laboratory. Animals were sacrificed, and the tissues immediately frozen and stored in liquid nitrogen. Tissues were obtained from male (n = 2) and female (n = 2) breeders as well as male (n = 2) and female (n = 2) non-breeders (subordinates). We analyzed brains from all eight individuals separately, but female ovaries were only large enough for individual analysis in breeders, whereas subordinate ovaries were so small that 3–5 of them had to be pooled for gene expression analyses. The testes of breeding and non-breeding males were not visually different, but breeder status was known because these males had previously sired pups.