A rise in prepubertal DHEA in the spiny mouse reveals the effect of adrenarche on the reproductive axis

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.