Caloric Load Preferentially Influences Epithelial Differentiation in the Murine Uterus to Drive Endometrial Hyperplasia
Student: Toni Allison
Major: Molecular Biology
Mentor: Dr. Christopher Kovisto, DVM
Department: MUSC Hollings Center
Caloric Load Preferentially Influences Epithelial Differentiation in the Murine Uterus to Drive Endometrial Hyperplasia
Endometrial hyperplasia is a precursor of type I endometrial carcinoma, the most common gynecological malignancy. The uterus undergoes cyclical patterns of endometrial proliferation and cell death, and these patterns are important in regards to fertility and cancer development. A strong epidemiological relationship between obesity and the prevalence of endometrial hyperplasia has been seen, in addition to the fact obese women are six times more likely to develop endometrial carcinoma than those who aren’t. In this study, we characterize the effects of diet on uterine morphology and protein expression in wildtype mice. Mice were fed one of three diets from 2 weeks until reaching 21 or 60 weeks of age: calorie-restricted, standard, or high fat. IHC was used to analyze their reproductive tracts before quantification. Our results demonstrated that increased caloric consumption results in glandular hyperplasia in the endometrium. There was also a calorie-dependent increase in the glandular cellularity and a calorie-dependent decrease in the luminal cellularity of the epithelium. This appears to be mediated through increased cell survival of the glands due to increased BCL2 expression, in addition to a phenotypic transition from luminal to glandular. These results show that the uterine epithelium has inherent nutrient-sensing functions causing it to be directly responsive to caloric intake that may be mediated through WNT-signaling.