Objective: To determine whether aminopeptidase N (APN) regulates the cycle-dependent bioavailability of interleukin-8 (IL-8) in the endometrium.
Design: Prospective study.
Setting: University medical center.
Patient(s): Women without endometrial pathology from the proliferative (n = 25) or secretory (n = 18) phase of the menstrual cycle.
Intervention(s): We first immunolocalized APN in the endometrium using an anti-APN antibody. We then determined the regulation of APN kinetic activity by sex steroids in endometrial stromal cell cultures.
Main Outcome Measure(s): Expression of APN in human endometrium throughout the menstrual cycle. Regulation of APN activity by estradiol and progesterone in cultured endometrial stromal cells.
Result(s): Immunohistochemistry of endometrial sections revealed staining of endometrial stroma throughout the menstrual cycle. There was no detectable staining in glandular cells. The expression of APN as detected by immunohistochemistry was significantly lower in the early proliferative phase. In cultured cells, estradiol inhibited APN activity in a concentration-dependent manner. Progesterone did not have a significant effect.
Conclusion(s): Stromal localization of APN in endometrium may explain the epithelial rather than stromal presence of IL-8 in vivo. Decreased expression of APN may increase IL-8 bioavailability thus contributing to angiogenesis and polymorphonuclear leukocyte chemotaxis in early proliferative phase. 相似文献
PURPOSE OF REVIEW: The long-held belief that 'the total number of oocytes present in the mammalian ovary is generated during fetal ovarian development with no additional oocyte formation during reproductive life' has recently been challenged. This review aims to summarize the scientific evidence and discuss the criticism put forth by other investigators in the field. In addition, we will entertain possible future directions, underlining clinical implications of de-novo oocyte formation during adulthood. RECENT FINDINGS: An initial report of oocyte generation from mouse stem cells in vitro was followed by a publication by Johnson et al., suggesting that new oocyte formation occurs in adult mice. Their more recent findings point toward bone marrow as a source of germline stem cells that give rise to new oocytes. SUMMARY: The findings of Johnson et al. strongly suggest the generation of oocytes from stem cells in the adult mouse. Criticism by prominent investigators in the field has been voiced but not yet adequately supported by experimental evidence. Crucially, independent confirmation of the findings of Johnson et al. is also lacking. If proven to occur in human, de-novo oocyte formation from stem cells would have significant implications for fertility preservation. 相似文献
Development of blood vessels takes place via two subsequent processes, vasculogenesis and angiogenesis. During vasculogenesis, formation of first blood vessels is achieved by differentiation of hemangiogenic stem cells from pluripotent mesenchymal cells, while during angiogenesis new blood vessels form from already existing vessels. The combination of our data with those from the literature leads us to depict the chronological steps of cell differentiation in the mesenchymal core of placental villi during vasculogenesis and angiogenesis. This current opinion will focus on the temporal and spatial expression of VEGF and its receptors VEGFR-1 and VEGFR-2, and the angiopoietin receptors Tie-1 and Tie-2 in parallel to vascular maturation in human placental villi during very early stages of placental development. There is evidence that the interplay of a variety of growth factors secreted from different cell types during development is needed to trigger as well as maintain placental vasculogenesis and angiogenesis. 相似文献
Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of many cellular proteins involved in apoptosis and proliferation. It was postulated that there is a higher Akt activity in endometriosis compared with normal endometrium, and that oestrogen may be one of the factors responsible for the high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in normal, eutopic and ectopic endometrial tissues were compared by immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt phosphorylation in stromal cells from eutopic endometrium was observed, when compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2–10 min) stimulated when endometrial stromal cells from normal and endometriosis patients were treated with 17β-oestradiol. In endometrial stromal cells from the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor antagonist) failed to antagonize the effect of oestradiol when combined with oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested that increased Akt phosphorylation may be related to the altered apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a critical role in the pathogenesis of endometriosis. 相似文献
Preeclampsia, a common pregnancy disorder associated with an increase in systemic inflammation, is the leading cause of maternal and fetal morbidity and mortality throughout the world. It is associated with shallow extravillous trophoblast invasion of the decidua, leading to uteroplacental blood flow that is inadequate for the developing fetal-placental unit. In preeclamptic women, interleukin-6 (IL-6) levels in plasma, but not placenta, are elevated, prompting evaluation of the decidua as a potential source of this excess, circulating IL-6. The current study found significantly higher immunohistochemical staining for IL-6 in decidual cells from preeclamptic versus preterm, gestational age-matched control placentas. Pro-inflammatory cytokines associated with the genesis of preeclampsia (i.e., tumor necrosis factor-alpha and interleukin-1beta) enhanced IL-6 mRNA levels and increased secreted IL-6 levels in first trimester leukocyte-free decidual cell incubations, as measured by real time quantitative RT-PCR, ELISA, and Western blotting. Therefore, decidual cell-derived IL-6 may contribute to excess circulating IL-6 levels that can promote both endothelial cell dysfunction (and subsequent vascular dysfunction) and the pathogenesis of preeclampsia whereas locally elevated IL-6 levels may contribute to an excess of decidual macrophages implicated in shallow extravillous trophoblast invasion of the decidua. 相似文献