Androgen-induced ferroptosis regulates seasonal testicular regression: insights into adaptive mechanisms of seasonal breeding.

BACKGROUND

Numerous animal species employ seasonal breeding strategies to cope with the challenges posed by environmental stress. Males exhibit periodic testicular development and spermatogenesis, which involves complex gene regulation and various cellular response mechanisms. However, the differences among species largely constrain our comprehensive understanding of this ecological adaptation phenomenon. Here, we explored the regulatory mechanism of seasonal testicular regression in plateau zokor (Eospalax baileyi), a typical seasonal breeding animal, through natural population survey and laboratory verification.

RESULTS

In natural populations, testicular regression was accompanied by reduction in androgen secretion and glutathione (GSH) concentration and the downregulated of GSH peroxidase 4 (Gpx4) gene, suggesting that androgen may induce ferroptosis to participate in the breeding regulation of plateau zokor. To this end, we carried out an indoor control experiment to deprive animals of androgen signals during the breeding season, and observed gonadal regression, abnormal spermatogenesis, and hormone level disorders. RNA-Seq analysis revealed, the induction of the expression of 658 genes in the testis of zokor in response to the regulation of androgen signaling. These differentially expressed genes were enriched in response to oxidative stress, GSH metabolism, and ferroptosis. By measuring GSH concentration and observing the downregulation of Gpx4, we confirmed that androgen is a regulatory factor that induces ferroptosis in the testis of plateau zokor.

CONCLUSIONS

Overall, we reported, for the first time, the role of ferroptosis in the regulation of seasonal breeding, providing a reference for understanding the regulatory mechanism underlying the seasonal breeding strategies of animals.