Spiny mice (Acomys cahirinus) are a distinctive rodent. Unlike conventional laboratory rodents, they secrete cortisol as their main glucocorticoid. They also have a menstrual cycle, a longer reproductive lifespan exceeding 4 years, and deliver precocial offspring with advanced organ development, similar to humans. Their neurobiology includes producing the neurosteroid dehydroepiandrosterone (DHEA), displaying gregarious behaviour, and preferring to socialise in large groups. They also exhibit nearly scarless wound healing. Overall, these features make spiny mice an excellent model for studying human developmental endocrinology and the regulation of these processes during pregnancy, childhood, adolescence, and ageing. This study aimed to characterise the development of circulating hormones and the transcriptional landscape of the adrenal gland in spiny mice.
Spiny mice were euthanised at 5, 10, 20, 35, 50 days (d) and 2 years of age (n=6/age/sex). Serum (50µL) was collected for liquid chromatography-mass spectrometry-based quantitative profiling of 15 adrenal steroids—including steroid precursors, androgens, glucocorticoids—while the adrenal glands were dissected for bulk-RNA sequencing.
Compared to newborn adrenals (5d), 2014 genes were differentially expressed across the 2-year study period. Most notably, transcript abundance of cytochrome P450 (CYP) enzymes (CYP17A1, CYP11A1, CYP21A2, CYP11B2) increased between 15-35d (adolescent-equivalence). Steroid precursor pregnenolone, cortisol and cortisol metabolites such as 20α-dihydrocortisol and 18-hydroxycortisol levels increased from 10d and peaked at 35d, while levels of androstenedione and progesterone increased gradually with age. Levels of corticosterone were stable and >25-fold less than cortisol.
The ontogeny of adrenal-related steroids and the transcriptome in spiny mice reveals distinct sex and age-specific patterns, with increases in adrenal-related steroids during 15-35 days of age, corresponding to adolescence in humans, and natural adrenal ageing at 2 years. Spiny mice thus present a novel animal model for investigating and modelling endocrinological phenomena such as adrenarche, fertility, and ageing to better understand health and disease.