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Vervet monkeys (Chlorocebus aethiops) are Old World nonhumans that display attenuated menstruation that requires detection by vaginal swab. The physiology underlying attenuated menstruation in this species has not been previously studied. To fill this gap, we evaluated endometrial cell proliferation, steroid receptor localization and expression of menstruation-associated matrix metalloproteinase (MMP) enzymes in vervets during natural and artificial menstrual cycles. The artificial cycles were induced by sequentially treating ovariectomized animals with estradiol (E(2)) and progesterone (P). Because menstrual flow is exceptionally light in this species, menses was detected by vaginal swab. We found that both natural and artificially cycled animals menstruated 3-5 days after the decline of P at the end of the cycle. As in other primates, P withdrawal at the end of artificial cycles triggered endometrial expression of MMPs, including MMP-1, 2, 3, 7, 10, 11, 13 and 26 transcripts. In both the natural and artificial menstrual cycle, menstrual sloughing was restricted to the upper one-fourth of the endometrium, and MMP-1 and 2 were strongly expressed by the stroma of the sloughing zone. MMP-7 was localized in the endometrial glands during late menses. As in macaques, epithelial cell proliferation was localized to the functionalis zone during the estrogen-dominated proliferative phase and to the basalis zone glands during the P-dominated secretory phase. Regulation of estrogen and progestin (or estradiol and progesterone) receptors was similar to that reported for macaques. Because strong similarities exist between the endometrium of vervets, macaques and women, we conclude that vervets can provide a useful animal model for studies on hormone regulation of menstruation.