Androgens, including testosterone and dihydrotestosterone, are steroid hormones essential for male sexual development, masculinisation, fertility, and lifelong health. Androgen deficiency (hypogonadism) can result in differences of sex development, reduced libido, subfertility, and undermasculinisation. Androgens are synthesised predominantly in the testes and, to a lesser extent, the adrenal glands via the canonical and alternate pathways. However, mouse models of androgen biosynthesis differ substantially from humans, highlighting the need for improved experimental models.
Marsupials have been instrumental in advancing our understanding of androgen biosynthesis and action. Their highly altricial young complete much of their sexual development ex utero, providing a unique opportunity to study these processes. The fat-tailed dunnart (Sminthopsis crassicaudata) represents a practical and more feasible marsupial model, although its androgen biosynthesis has not previously been characterised.
Here, we present the most comprehensive characterisation of androgen biosynthesis in a marsupial to date. Steroidogenesis was examined at three key developmental stages: postnatal day (d)25 (sexual development), d150 (masculinisation), and d250 (sexual maturity following a complete round of spermatogenesis). Mass spectrometry was used to quantify 17 steroids, including androgens and precursors from both the canonical and alternate pathways, in testes, adrenal glands, and in circulation at each timepoint. Steroid profiles demonstrate that androgen biosynthetic pathway utilisation shifts across development. Expression of key steroidogenic enzymes was also examined in the testes and adrenal glands, and functional comparisons with human and mouse enzymes are being undertaken to determine whether the dunnart more closely reflects human androgen biosynthesis.
These findings establish the fat-tailed dunnart as a promising model for investigating mammalian androgen biosynthesis and sexual development, with potential advantages over current mouse models. They also provide a foundation for conservation applications, including improved breeding programs and population monitoring in marsupial species.