Demonstration of angiogenin in human endometrium and its enhanced expression in endometrial tissues in the secretory phase and the decidua

Angiogenesis is thought to be crucial for normal physiology of the endometr ium, where dynamic vascular remodeling occurs during the menstrual cycle an d pregnancy. We investigated the presence of angiogenin, a potent inducer o f angiogenesis, and the regulatory mechanisms of its production in the huma n endometrium. Western blot analysis demonstrated that angiogenin protein e xpression increased by 3- to 4-fold in the endometrium in the mid and late secretory phases and in early gestation relative to that during the prolife rative phase. Quantitative mRNA analysis showed the similar tendency in the expression of angiogenin mRNA in the endometrium, with the highest levels observed in the mid and late secretory phases and early gestation. An immun ohistochemical study showed that angiogenin was expressed in both stromal c ells and epithelial cells, with indistinguishable intensity between these c ells regardless of phases of the menstrual cycle. In support of the Western blot analysis, the intensity of staining appeared to be highest in the mid to late secretory phases relative to other phases. Consistent with these in vivo results; decidualized cultured stromal cells, after treatment with progesterone or progesterone plus E2, exhibited the c apacity to secrete significantly increased amounts of angiogenin compared w ith untreated or E2 alone-treated control group. Both the treatment with (B u)(2)cAMP and hypoxic conditions stimulated angiogenin secretion by stromal cells. For isolated epithelial cells, hypoxia stimulated angiogenin secret ion, whereas (Bu)2cAMP had no appreciable effect. In summary, we demonstrat ed the presence of angiogenin in human endometrium and its possible local r egulatory factors, such as progesterone, cAMP, and hypoxia. These findings along with its enhanced expression in the endometrium in the secretory phas e and in decidual tissues raise the possibility that angiogenin may play a role in establishing pregnancy.