1002 CHAPTER 22 The Female Genital Tract down-regulates the expression of estrogen receptor in both the glands and the stroma, and as a result endometrial proliferation is suppressed. Progesterone also promotes the differentiation of the glands and causes functional changes in the stromal cells. Endometrial stem cells have been identi- fied that likely have a central role in the regeneration of the endometrium after menses. They may also contribute to the development of ectopic endometrial tissue and endo- metrial cancer. FUNCTIONAL ENDOMETRIAL DISORDERS (DYSFUNCTIONAL UTERINE BLEEDING) Although abnormal uterine bleeding can be caused by well-defined pathologic conditions, such as chronic endo- metritis, endometrial polyps (Fig. 22.20C), submucosal leiomyomas (see Fig. 22.20D), or endometrial neoplasms, it most commonly stems from hormonal disturbances that produce dysfunctional uterine bleeding (Table 22.3). This is a clinical term for uterine bleeding that lacks an underlying structural abnormality. As discussed earlier, the normal increase in ground substance and edema between the stromal cells followed by stromal cell hypertrophy, increased cytoplasmic eosinophilia (predecidual change), and a resurgence of stromal mitoses (see Fig. 22.19C). Predecidual changes spread throughout the functio- nalis and are accompanied by a sparse infiltrate of neutrophils and lymphocytes, which in this context are considered normal. • With the dissolution of the corpus luteum and the subsequent drop in progesterone levels, the functionalis degenerates and bleeding into the stroma occurs, followed by stromal breakdown and onset of the next menstrual cycle