Heat Stress-Induced Male Reproductive Dysfunction in Brandt's Vole (Lasiopodomys brandtii): A Central Role for Endoplasmic Reticulum Stress.

Rising global temperatures pose a serious threat to wild small mammals' population persistence. In this study, we investigated the molecular mechanisms underlying heat-induced testicular impairment in Brandt's vole (Lasiopodomys brandtii), a dominant small mammal species of the Eurasian temperate steppe. Adult males were subjected to short-term heat exposure at 37 °C, 39 °C, and 41 °C. Heat stress at temperatures ≥ 39 °C significantly reduced the testicular index and caused histopathological damage. Integrated transcriptomic and data-independent acquisition proteomic analyses revealed significant enrichment of pathways related to endoplasmic reticulum protein processing and barrier function. Further molecular validation showed significant upregulation of key ER stress-related markers, including total eIF2α, ATF4, ATF6B, and XBP1, suggesting the potential involvement of the unfolded protein response. Together, these results identify endoplasmic reticulum stress as a key mediator of heat-induced testicular injury and highlight that 41 °C leads to marked activation of ER stress markers and severe testicular impairment in Brandt's voles, even following short-term exposure.