Adrenarche in the spiny mouse (Acomys dimidiatus) reveals effects of prepubertal DHEA on the reproductive axis and PCOS-like phenotypes

ABSTRACT: Adrenarche, characterized by rising adrenal dehydroepiandrosterone (DHEA) levels, precedes puberty and has been implicated in reproductive maturation, and disorders like polycystic ovary syndrome (PCOS). However, the mechanisms by which DHEA influences the hypothalamic-pituitary-gonadal (HPG) axis remain poorly understood, largely due to the absence of an appropriate animal model. The spiny mouse (genus Acomys), which has a prolonged juvenile phase and endogenous prepubertal DHEA production, provides a valuable system to investigate the effects of early-life exposure to DHEA. We confirmed the spiny mouse prepubertal rise in circulating DHEA levels, which occurs independently of HPG axis activation. Transcriptomic analysis revealed increased ovarian expression of steroidogenic and estrogen-responsive genes, suggesting possible effects of DHEA. We show in vitro that DHEA induces Prlr and Prl expression seemingly via the estrogen receptor. Adrenalectomy (Adx) followed by DHEA “rescue” (AdxDHEA) revealed that DHEA can be synthesized and metabolized outside the adrenal glands. Ovarian transcriptomes from AdxDHEA mice exhibited extensive changes, including upregulation of immune response-related genes, and downregulation of cholesterol-metabolism and estrogen-synthesis genes, most notably Cyp19a1. The reduced Cyp19a1 expression is likely due to elevated Amhr2, and was accompanied by a high androgen-to-estrogen ratio, indicating a DHEA-induced, PCOS-like phenotype. The rise in DHEA during an extended juvenile phase establishes the spiny mouse as a suitable model for studying the consequences of elevated DHEA in childhood. Our findings reveal that prepubertal exposure to DHEA alters ovarian gene expression and steroidogenesis, providing mechanistic insight into how early androgen excess may predispose to reproductive dysfunction.

ORGANISM(S): Acomys dimidiatus

PROVIDER: GSE306393 | GEO | 2026/05/14

REPOSITORIES: GEO