Absence of CD9 reduces endometrial VEGF secretion and impairs uterine repair after parturition.

In mammals, uterine epithelium is remodeled cyclically throughout adult life for pregnancy. Despite the expression of CD9 in the uterine epithelium, its role in maternal reproduction is unclear. Here, we addressed this issue by examining uterine secretions collected from patients undergoing fertility treatment and fertilization-competent Cd9(-/-) mice expressing CD9-GFP in their eggs (Cd9(-/-)TG). CD9 in uterine secretions was observed as extracellular matrix-like feature, and its amount of the secretions associated with repeated pregnancy failures. We also found that the litter size of Cd9(-/-)TG female mice was significantly reduced after their first birth. Severely delayed re-epithelialization of the endometrium was then occurred. Concomitantly, vascular endothelial growth factor (VEGF) was remarkably reduced in the uterine secretions of Cd9(-/-)TG female mice. These results provide the first evidence that CD9-mediated VEGF secretion plays a role in re-epithelialization of the uterus.

Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity.

BACKGROUND: Recently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF. METHODS: Of the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann-Whitney U-test and the chi-square test. RESULTS: Of the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively). CONCLUSIONS: A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity.

Uterine cavity matrix metalloproteinases and cytokines in patients with leiomyoma, adenomyosis or endometrial polyp.

OBJECTIVE: To determine whether leiomyoma, adenomyosis and endometrial polyps are associated with changes in uterine cavity matrix metalloproteinases (MMP-2 and MMP-9) and cytokines. STUDY DESIGN: Uterine cavity irrigation was performed in women with leiomyoma, adenomyosis and endometrial polyps, and in women with a normal uterus. MMP-2 and MMP-9 were assayed in the uterine washings by gelatin zymography. For individual subjects, the total MMP level was obtained by adding the semi-quantitative scores of band densities related to gelatinases in the zymograms. Interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF-beta1) were measured using enzyme-linked immunosorbant assay (ELISA) kits. RESULTS: The uterine cavity of patients with leiomyoma, adenomyosis and endometrial polyps had significantly higher MMP scores than controls. Although the mean IL-1beta levels were elevated in uteri harboring a pathology compared with the normal uteri, the cytokine was significantly elevated only in the adenomyotic group. Significantly elevated levels of IFN-gamma were found in uteri with leiomyoma and endometrial polyps. Uterine washings from leiomyoma and adenomyosis contained significantly elevated mean levels of TGF-beta1 compared with controls, while TNF-alpha was significantly higher only in leiomyoma. When uterine cytokine levels were compared in relation to individual MMP levels a significant relationship was found between TGF-beta1 and elevated levels of MMP-9 and total MMPs in leiomyoma. A significant relationship was also found between IL-1beta and elevated levels of MMP-2, MMP-9 and total MMPs in the endometrial polyp group. CONCLUSION: The uterine cavity in leiomyoma, adenomyosis and endometrial polyps contains elevated levels of MMPs and cytokines compared with the normal uterus. In some pathologies elevated cytokines are associated with elevated MMPs.

Photosynthetic limitations of a halophyte sea aster (Aster tripolium L) under water stress and NaCl stress.

To understand the mechanisms of salt tolerance in a halophyte, sea aster ( Aster tripolium L.), we studied the changes of water relation and the factors of photosynthetic limitation under water stress and 300 mM NaCl stress. The contents of Na(+) and Cl(-) were highest in NaCl-stressed leaves. Leaf osmotic potentials ( Psi(s)) were decreased by both stress treatments, whereas leaf turgor pressure ( Psi(t)) was maintained under NaCl stress. Decrease in Psi(s) without any loss of Psi(t) accounted for osmotic adjustment using Na(+) and Cl(-) accumulated under NaCl stress. Stress treatments affected photosynthesis, and stomatal limitation was higher under water stress than under NaCl stress. Additionally, maximum CO(2) fixation rate and O(2) evolution rate decreased only under water stress, indicating irreversible damage to photosynthetic systems, mainly by dehydration. Water stress severely affected the water relation and photosynthetic capacity. On the other hand, turgid leaves under NaCl stress have dehydration tolerance due to maintenance of Psi(t) and photosynthetic activity. These results show that sea aster might not suffer from tissue dehydration in highly salinized environments. We conclude that the adaptation of sea aster to salinity may be accomplished by osmotic adjustment using accumulated Na(+) and Cl(-), and that this plant has typical halophyte characteristics, but not drought tolerance.