Arginine and putrescine ameliorate heat stress-induced testicular inflammation and apoptosis via inhibiting endoplasmic reticulum stress in mice.

Heat stress can severely impair male reproductive performance. Endoplasmic reticulum stress (ERS) is recognized as an early cellular response to stress, which can subsequently induce inflammation and apoptosis, thereby reducing semen quality. In this study, arginine, putrescine, and 4-phenylbutyric acid (4-PBA; an ERS inhibitor) were administered by gavage to a heat-stressed ICR mouse model subjected to seven days of heat exposure, in order to evaluate their effects on testicular function and the underlying mechanisms. Supplementation with arginine, putrescine, or 4-PBA significantly ameliorated heat stress-induced testicular damage and the decline in sperm quality in male mice. Specifically, the mRNA expression of Acrv1, Izumo3, and Tjp1 was markedly upregulated. In contrast, the number of TUNEL-positive testicular cells was significantly reduced, while the mRNA expression of apoptotic markers Bax and Caspase12 was downregulated. Moreover, the expression of ERS- and inflammation-related genes (Grp78, Perk, IRE1, XBP1s, TLR4, and NF-κB) was significantly decreased. In conclusion, heat stress induces testicular dysfunction and inflammation. Both arginine and its metabolite putrescine alleviate heat stress-induced testicular impairment by reducing ERS and inflammatory responses, with arginine showing stronger protective effects than putrescine.