Dexamethasone acutely regulates endocrine parameters in stallions and subsequently affects gene expression in testicular germ cells

• Dexamethasone acutely decreases circulating testosterone in stallions.
• After two weeks, dexamethasone decreased expression of two genes in stallion testes.
• The two regulated genes, DNAJC4 and CATSPER1, are expressed only in male germ cells.

Testicular steroidogenesis and spermatogenesis are negatively impacted by stress-related hormones such as glucocorticoids. The effects of two injections of a therapeutic dose of dexamethasone (a synthetic glucocorticoid, 0.1 mg/kg; i.v.) given 24 h apart to each of three stallions were investigated and compared to three saline-injected control stallions. Dexamethasone decreased circulating concentrations of cortisol by 50% at 24 h after the initial injection. Serum testosterone decreased by a maximum of 94% from 4 to 20 h after the initial injection of dexamethasone. Semen parameters of the dexamethasone-treated stallions were unchanged in the subsequent two weeks. Two weeks after treatment, stallions were castrated. Functional genomic analyses of the testes revealed that, of eight gene products analyzed, dexamethasone depressed concentrations of heat shock protein DNAJC4 and sperm-specific calcium channel CATSPER1 mRNAs by more than 60%. Both genes are expressed in germ cells during spermiogenesis and have been related to male fertility in other species, including humans. This is the first report of decreased DNAJC4 and CATSPER1 mRNA concentrations in testes weeks after dexamethasone treatment. Concentrations of these mRNAs in sperm may be useful as novel markers of fertility in stallions.