Alterations in expression of endometrial milk fat globule-EGF factor 8 (MFG-E8) and leukemia inhibitory factor (LIF) in patients with infertility and endometriosis.

OBJECTIVE: The aim of this study was to compare the endometrial expression of milk fat globule-EGF factor 8 (MFG-E8), its receptor integrin αvß3, and leukemia inhibitory factor (LIF) in patients with endometriosis and infertility and in healthy fertile patients during the window of implantation. METHODS: Five patients with peritoneal endometriosis and infertility (case group) and four healthy fertile patients (control group) were recruited. All patients were either diagnosed with or ruled out for endometriosis by laparoscopic surgery; the case group underwent surgery for infertility investigation and the control group for tubal ligation. Endometrial biopsies were performed in all patients during the window of implantation (LH+8 to LH+10), and then the samples were analyzed by immunochemistry for MFG-E8, integrin αvß3, and LIF. RESULTS: In patients with endometriosis and infertility, expression of MFG-E8 was significantly increased in the glandular epithelium when compared to healthy fertile patients (p<0.001). Moreover, LIF expression was lower in patients with endometriosis and infertility (p<0.05). Nevertheless, we found no difference in integrin αvß3 expression between the groups (p=0.084). CONCLUSION: This study showed for the first time that MFG-E8 expression is impaired in the endometrium of patients with endometriosis and infertility during the window of implantation. Moreover, LIF is also diminished in the endometrium of these patients as shown before.

MFG-E8, a clearance glycoprotein of apoptotic cells, as a new marker of disease severity in chronic obstructive pulmonary disease

Milk fat globule epidermal growth factor 8 (MFG-E8) is an opsonin involved in the phagocytosis of apoptotic cells. In patients with chronic obstructive pulmonary disease (COPD), apoptotic cell clearance is defective. However, whether aberrant MFG-E8 expression is involved in this defect is unknown. In this study, we examined the expression of MFG-E8 in COPD patients. MFG-E8, interleukin (IL)-1β and transforming growth factor (TGF)-β levels were measured in the plasma of 96 COPD patients (93 males, 3 females; age range: 62.12±10.39) and 87 age-matched healthy controls (85 males, 2 females; age range: 64.81±10.11 years) using an enzyme-linked immunosorbent assay. Compared with controls, COPD patients had a significantly lower plasma MFG-E8 levels (P<0.01) and significantly higher plasma TGF-β levels (P=0.002), whereas there was no difference in plasma IL-1β levels between the two groups. Moreover, plasma MFG-E8 levels decreased progressively between Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and GOLD IV stage COPD. Multiple regression analysis showed that the forced expiratory volume in 1 s (FEV1 % predicted) and smoking habit were powerful predictors of MFG-E8 in COPD (P<0.01 and P=0.026, respectively). MFG-E8 was positively associated with the FEV1 % predicted and negatively associated with smoking habit. The area under the receiver operating characteristic curve was 0.874 (95% confidence interval: 0.798-0.95; P<0.01). Our findings demonstrated the utility of MFG-E8 as a marker of disease severity in COPD and that cigarette smoke impaired MFG-E8 expression in these patients.

Malignant transformation of rat kidney induced by environmental substances and estrogen.

The use of organophosphorous insecticides in agricultural environments and in urban settings has increased significantly. The aim of the present study was to analyze morphological alterations induced by malathion and 17ß-estradiol (estrogen) in rat kidney tissues. There were four groups of animals: control, malathion, estrogen and combination of both substances. The animals were injected for five days and sacrificed 30, 124 and 240 days after treatments. Kidney tissues were analyzed for histomorphological and immunocytochemical alterations. Morphometric analysis indicated that malathion plus estrogen-treated animals showed a significantly (p < 0.05) higher grade of glomerular hypertrophy, signs of tubular damage, atypical proliferation in cortical and hilium zone than malathion or estrogen alone-treated and control animals after 240 days. Results indicated that MFG, ER-α, ER-ß, PgR, CYP1A1, Neu/ErbB2, PCNA, vimentin and Thrombospondin 1 (THB) protein expression was increased in convoluted tubules of animals treated with combination of malathion and estrogen after 240 days of 5 day treatment. Malignant proliferation was observed in the hilium zone. In summary, the combination of malathion and estrogen induced pathological lesions in glomeruli, convoluted tubules, atypical cell proliferation and malignant proliferation in hilium zone and immunocytochemical alterations in comparison to control animals or animals treated with either substance alone. It can be concluded that an increased risk of kidney malignant transformation can be induced by exposure to environmental and endogenous substances.