We have found that juvenile rhesus monkeys can be treated with exogenous steroids to induce artificial menstrual cycles. Our goal was to develop a cycling monkey model in animals of smaller size for studies of rare and expensive growth factors. Non-cycling juvenile monkeys (approximately 1 year old) were ovariectomized and treated sequentially with implants of estradiol (E2 ) for 14 days and then E2 + progesterone (P) for 14 days. P implants were then removed (E2 implant remaining) to begin the next cycle. All the juvenile monkeys menstruated for 2-3 days after P withdrawal. Histological analysis of reproductive tract tissues revealed that treatment with E2 + P for 14 days resulted in a secretory differentiation of the endometrium characterized by sacculation of the glands and expansion of the endometrial stroma. E2 + P for 14 days resulted in a full suppression of oviductal ciliation. On day 4 of P-withdrawal, the endometrium was healing from menstruation, apoptotic cell death was evident in the endometrial basalis, and epithelial cell proliferation was stimulated in the oviductal fimbriae. In monkeys 14 days after P withdrawal (14 days of E2 alone), the endometrium was proliferative, and the oviduct fully ciliated. These changes are identical to those observed in adult rhesus monkeys. These data are the first to show that the uterus and oviducts of 1-year-old rhesus juveniles can be experimentally """"""""matured"""""""" and used in analytic studies of growth factor action.
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