LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity

LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity

Blog Article

Tissue radiosensitivity plays a critical role in the overall outcome of radiation therapy.Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window.Limited clinical data have suggested a difference in male and female radiotherapy outcomes.Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity.In this manuscript, we demonstrated sex-specific differences in intestinal epithelial radiosensitivity.

In a mouse model of abdominal irradiation, we observed a significant increase in oxidative stress and injury in Outdoor Dining Bench with Cushion males compared to females.Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation-induced toxicity.However, sex-specific differences in Outdoor Sectional with Bench intestinal radiosensitivity were not dependent on sex hormones, as we demonstrated similar sex-specific radiosensitivity differences in pre-pubescent mice.In an ex vivo study, we found that patient-derived intestinal organoid (PID) from males showed higher sensitivity to radiation compared to females as evident from loss of budding crypts, organoid size, and membrane integrity.Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation-induced upregulation of mitochondrial oxidative metabolism in males compared to females, a possible mechanism for radiosensitivity differences.