Estrogen enhances female small intestine epithelial organoid regeneration

Abstract Promoting intestinal epithelial regeneration remains a major medical challenge. Female patients taking nonsteroidal anti-inflammatory drugs are less likely to have upper gastrointestinal bleeding and ulcers than males. Using a nonsteroidal anti-inflammatory drug-induced intestinal damage mouse model, we verified that female mice recover faster than males following acute intestinal insult. Using ex vivo intestinal organoid cultures, we showed that estrogen is necessary and sufficient in enhancing the female organoid formation from breached isolated crypts via the estrogen receptor &bgr; receptor. Thus, estrogen promotes female intestinal epithelial organoid regeneration to lower the incidence of intestinal bleeding and ulceration. Animal studies were approved by University of Utah IACUC under protocol number 16-05012 and 18-02010.