PT  - JOURNAL ARTICLE
AU  - Eskeatnaf Mulugeta
AU  - Lucile Marion-Poll
AU  - David Gentien
AU  - Stefanie B. Ganswindt
AU  - André Ganswindt
AU  - Nigel C. Bennett
AU  - Elizabeth H. Blackburn
AU  - Chris G. Faulkes
AU  - Edith Heard
TI  - Molecular insights into the pathways underlying naked mole-rat eusociality
AID  - 10.1101/209932
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 209932
4099  - http://biorxiv.org/content/early/2017/10/27/209932.short
4100  - http://biorxiv.org/content/early/2017/10/27/209932.full
AB  - Background Eusociality is the highest level of social organization and naked mole-rats (NMR)s are amongst the few mammals showing this unique social behavior; nevertheless, little is known about the molecular mechanisms underlying the eusociality of NMRs.Results Gene expression profiling of NMR brain and gonads (ovary and testis), from animals belonging to different reproductive castes, revealed robust gene expression differences between reproductive and non-reproductive members of NMR colonies. In the brain, dopaminergic pathways appear to be potential players in NMR eusocial behaviour. Breeding animals (queens and breeding males) showed increased expression of genes involved in dopamine metabolism. Using immunohistochemistry, we notably found these differences to be in dopaminergic hypothalamic areas, which provide inhibitory control over the secretion of prolactin, amongst other regions. Furthermore, plasma prolactin concentrations were elevated in many non-breeders (of both sexes), often reaching levels exceeding that of pregnant or lactating queens, suggesting a role for hyperprolactinaemia in socially-induced reproductive suppression. We also found that the ovaries of non-breeding females are arrested at pre-pubertal stage. They contained fewer supporting stromal cells compared to queens, and had very low expression of the aromatase gene Cyp19A1 (a key enzyme in estrogen synthesis) compared to non-breeding females. In the testes, genes involved in post meiosis spermatogenesis and sperm maturation (Prm1, Prm2, Odf3 and Akap4) were highly expressed in breeding males compared to non-breeders, explaining the low sperm number and impaired sperm motility characteristic of non-breeding males.Conclusions Our study suggests that extreme reproductive skew, one of the defining features of eusociality, is associated with changes in expression of key components of dopamine pathways, which could lead to hypogonadism and a lifetime of socially-induced sterility for most NMRs.NMRNaked mole-ratsLHLuteinizing hormoneGnRHGonadotrophin releasing hormoneRNA-seqRNA-sequencingPCAPrincipal component analysisQQueenQs_TrQueen technical replicateNBFNon-breeding femalesNBF_TrNon breeding female technical replicateNBMNon-breeding malesBMBreeding malesCPMCounts per millionDEGDifferentially expressed genesGOGene ontologyQgenes Queen genesTH/ThTyrosine hydroxylaseFSHFollicle-stimulating hormonePGCsPrimordial germ cellsPRLProlactinbpBase pairIFImmunofluorescenePValuep-valuelogCPMCounts per million in log scalelogFCLog fold changeFDRFalse discovery rateBHBenjamini-Hochberg