Histologic response of normal human endometrium to steroid hormones in athymic mice

Despite the widespread use of hormonal therapy for menopausal symptoms, oral contraception, and treatment of metastatic breast carcinoma, information concerning the histologic and biologic effects of individual sex steroids on the human endometrium remains incomplete. Repetitive endometrial biopsy is impractical, and ethical constraints limit the dosage and duration of administration for some steroids. The ovariectomized athymic mouse was investigated as a host for human endometrium in which the hormonal milieu may be manipulated and the histologic response determined. Minced proliferative-phase endometrium from hysterectomy specimens of normally cycling women was inserted into the subcutis of 4- to 6-week-old mice. Proliferation of endometrial gland cells occurred in the transplanted endometrium of estradiol-treated mice, while the complete sequence of secretory-phase events, including subnuclear vacuolization, luminal secretion, and decidualization of stroma, was observed during a 14-day period of treatment with estradiol and progestin (medroxyprogesterone acetate). Progestin treatment alone also caused secretory-phase changes, but the response was delayed and appeared weaker. The transplanted endometrium in control mice appeared to be inactive. These observations provide support for the use of this model to study the histologic response of human endometrium to sex steroids.