Dihydroartemisinin exposure impairs porcine ovarian granulosa cells by activating PERK-eIF2α-ATF4 through endoplasmic reticulum stress.

摘要: Abstract Dihydroartemisinin (DHA) is an artemisinin derivative commonly used in malaria therapy, and a growing number of studies have focused on the potent anticancer activity DHA. However, reproductive toxicity drugs major concern for young female cancer patients. Previous suggested that DHA can cause embryonic damage affect oocyte maturation. Here, we explored side effects exposure ovarian somatic cells. We exposed porcine granulosa cells to 5 μM 40 μM 24 h or 48 h vitro. inhibited cell viability dose-dependent manner and, treatment group, enhanced apoptotic rate. observed levels intracellular calcium, mitochondrial ATP concentration were elevated with treatment. In DHA, mRNA endoplasmic reticulum stress-related genes GRP78 ATF4 increased. Furthermore, analysis unfolded protein response signaling pathway showed P-PERK, P-eIF2α, upregulated by exposure. These results demonstrate cells, induces stress then activates PERK/eIF2α/ATF4 pathway, thus providing insight into mechanism underlying DHA-induced toxicity, giving reference use females.