Lack of sexual dimorphism in femora of the eusocial and hypogonadic naked mole-rat: a novel animal model for the study of delayed puberty on the skeletal system

Abstract

Sex steroid hormones are major determinants of bone morphology and quality and are responsible for sexually dimorphic skeletal traits. Hypogonadism results in suboptimal skeletal development and may lead to an increased risk of bone fracture later in life. The etiology of delayed puberty and/or hypothalamic amenorrhea is poorly understood, and experimental animal models addressing this issue are predominantly based upon short-term experimental induction of hormonal suppression via gonadotropin releasing hormone antagonists (GnRH-a). This acute change in hormone profile does not necessarily emulate the natural progression of hypogonadic bone disorders. We propose a novel animal model with which to explore the effects of chronic hypogonadism on bone quality, the naked mole-rat (NMR; Heterocephalus glaber). This mouse-size rodent may remain reproductively suppressed throughout its life, if it remains as a subordinate within the eusocial mole-rat colony. NMRs live in large colonies with a single dominant breeding female. She, primarily by using aggressive social contact, naturally suppresses the hypothalamic gonadotropic axis of subordinate NMRs and thereby their reproductive expression. However, should an NMR be separated from the dominant breeder, within less than a week reproductive hormones may become elevated and the animal attains breeding status. We questioned if sexual suppression of subordinates impact upon the development and maintenance of the femora and lead to a sexually indistinct monomorphic skeleton. Femora were obtained from male and female NMRs that were either non-breeders (subordinate) or breeders at the time of sacrifice. Diaphyseal cross-sectional morphology, metaphyseal trabecular micro-architecture and tissue mineral density of the femur were measured using microcomputed tomography and diaphyseal mechanical properties were assessed by four-point bending tests to failure. Subordinates were sexually monomorphic and showed no significant differences in body weight or femoral bone structure and quality between males and females. Femora of subordinate females differed significantly from that of breeding animals, whereas in males, the divergent trend among breeders and non-breeders did not reach statistical significance. Subordinate NMRs, naturally suppressed from entering puberty, may prove to be a useful model to tease apart the relationship between bone morphology and hypogonadism and evaluate skeletal development during pubertal maturation.