(1) Background: The microbial phase in the vaginal environment has been found to regulate the physiological activity of host cells. Studies have demonstrated that abnormal microbial growth in the vagina and a significant reduction in the proportion of lactic acid bacteria promote the occurrence of spontaneous preterm birth (sPTB). However, the contributing mechanism remains unknown. (2) Methods: This study uses extracellular vesicles (EVs) secreted by the probiotic Lactobacillus crispatus, commonly found in the vagina, to explore their potential to attenuate placental cells caused by oxidative stress induction. (3) Results: We found that L. crispatus-derived EVs improved Akt phosphorylation and attenuated both cell senescence and death in placental cells caused by oxidative stress induction. In addition, L. crispatus-derived EVs enhanced the resistance to H2 O2 induction mediated by increasing mitochondrial fusion. (4) Conclusion: This is the first study to demonstrate that L. crispatus in the vagina can not only regulate the physiological functions of placental cells through the delivery of L. crispatus-EVs but also reduce cell senescence. As cell senescence is related to the occurrence of sPTB, these results indicate that maintaining the population of L. crispatus in the vaginal environment should be an adjuvant treatment strategy to avoid sPTB.
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