Socially regulated reproductive development: Analysis of GnRH‐1 and kisspeptin neuronal systems in cooperatively breeding naked mole‐rats (Heterocephalus glaber)

Abstract

In naked mole-rat (NMR) colonies, breeding is monopolized by the queen and her consorts. Subordinates experience gonadal development if separated from the queen. To elucidate the neuroendocrine factors underlying reproductive suppression/development in NMRs, we quantified plasma gonadal steroids and GnRH-1- and kisspeptin-immunoreactive (ir) neurons in subordinate adults and in those allowed to develop into breeders, with or without subsequent gonadectomy. In males and females, respectively, plasma testosterone and progesterone are higher in breeders than in subordinates. No such distinction occurs for plasma estradiol; its presence after gonadectomy and its positive correlation with adrenal estradiol suggest an adrenal source. Numbers of GnRH-1-ir cell bodies do not differ between gonad-intact breeders and subordinates within or between the sexes. As in phylogenetically related guinea pigs, kisspeptin-ir processes pervade the internal and external zones of the median eminence. Their distribution is consistent with actions on GnRH-1 neurons at perikaryal and/or terminal levels. In previously investigated species, numbers of kisspeptin-ir cell bodies vary from substantial to negligible according to sex and/or reproductive state. NMRs are exceptional: irrespective of sex, reproductive state, or presence of gonads, substantial numbers of kisspeptin-ir cell bodies are detected in the rostral periventricular region of the third ventricle (RP3V) and in the anterior periventricular (PVa), arcuate, and dorsomedial hypothalamic nuclei. Nevertheless, the greater number in the RP3V/PVa of female breeders compared with female subordinates or male breeders suggests that emergence from a hypogonadotrophic state in females may involve kisspeptin-related mechanisms similar to those underlying puberty or seasonal breeding in other species.

Social regulation of adult neurogenesis in a eusocial mammal

“…In addition to an imperforate vagina and underdeveloped ovaries, subordinate females display lower levels of circulating testosterone, progesterone and LH, as well as a less profound LH response to GnRh than queens (Faulkes et al, 1990a;1990b;1991;Jarvis, 1991). By contrast, status differences in female estradiol levels have not been detected previously (Zhou et al, 2013). Whether this finding reflects extra-gonadal sources of estradiol, or sampling across the reproductive cycle remains to be determined.…”

“…As ovariectomy in traditional laboratory rodents suppresses hippocampal cell proliferation in the short- , but not long-term (Tanapet et al, 2005;LaGace et al, 2007), it is possible that ovariectomised rats and reproductively suppressed naked molerats maintain high levels of hippocampal neurogenesis via compensatory mechanisms, such as extra-gonadal estrogen production. This possibility is supported by reports of adrenal estradiol synthesis in female naked mole-rats, and comparable concentrations of plasma estradiol among intact breeders, GDX breeders, and subordinates (Zhou et al, 2013). While it may be that estrogen mediates socially induced changes in SVZ-derived neurogenesis (Smith et al, 2001), it is also possible that extra-gonadal hormones such as prolactin regulate neurogenesis in the PCx and BLA (Mak et al, 2007).…”

“…While the low neurogenic capacity observed in breeding females lines up with research demonstrating that queens have higher levels of circulating progesterone than same-sex subordinates (Zhou et al, 2013), low DCX expression did not extend to females given the opportunity to transition status. Both groups were exposed to an environment conducive to reproductive activation, yet neurogenesis was higher in the DG and…”

“…For males, reproductive suppression entails lower levels of urinary testosterone and plasma luteinizing hormone (LH) in subordinates than breeders, small testis, and blunted LH release in response to exogenous gonadotropin releasing hormone (GnRh). While gametogenesis does occur in some subordinate males, rates are low and sperm are nonmotile (Faulkes et al, 1991;1994, Faulkes andAbbott, 1991;Clarke and Faulkes, 1998;Zhou et al, 2013). For females, sexual repression is more pronounced, and ovulation is suppressed completely.…”

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

“…In colonies of up to 300 individuals, breeding is restricted to one dominant female (the queen) and one to three males, with other colony members being socially subordinate and reproductively suppressed. Though pronounced alterations in neural and endocrine function accompany the change (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47), male and female subordinates are capable of transitioning to breeding status following the death/removal of breeders or separation from the colony. Indeed, although colony-housed subordinates have low progesterone (P), testosterone (T), and luteinizing hormone (LH) concentrations compared with same-sex breeders (37,38), they show elevated urinary P and T levels within 1 wk of separation from the colony (37,40), with females developing a perforated vagina during that time (37).…”