Possible Role of TGF-ß1, MMP-2, E-CAD, ß-Catenin and Antioxidants in Pathogenesis of Placenta Accreta.

OBJECTIVES: Placenta accreta (PA) can be life-threatening due to postpartum hemorrhage and may lead to cesarean hysterectomy. We investigated the expression of Matrix metalloproteinase-2 (MMP-2), ß-catenin, E-cadherin (E-CAD), transforming growth factor ß1 (TGF-ß1), glutathione peroxidase 1 (GPx-1), reduced glutathione (GSH) and superoxide dismutase (SOD) in PA compared to controls to determine if alterations may contribute to PA. Materials and methods: Twenty six PA and 31 controls were evaluated immunohistochemically for expression of MMP-2, ß-catenin and E-CAD on villous and extravillous trophoblasts. TGF-ß1 and GPx-1 mRNA levels were evaluated by rt-PCR. We measured biochemical levels of GSH and SOD. Results: Significant increases of MMP-2 immunoexpression, GPx-1 mRNA, SOD and GSH levels, decreases in immunoexpression of E-CAD and ß-catenin and TGF-ß1 mRNA were found in PA. Conclusion: These findings suggest that loss of cell-cell adhesion and increased antioxidants level may have a role in PA.

Cilostazol protects against cyclophosphamide-induced ovarian toxicity in female rats: role of cAMP and HO-1.

Purpose: Cancer rates have been increased among women of reproductive age nowadays. Hence, many young female will be exposed to chemotherapeutic agents as cyclophosphamide (CP), carrying the hazards on female fertility. Cilostazol is a selective phosphodiesterase-3 inhibitor drug which exhibits antioxidant, anti-inflammatory, and anti-apoptotic activities. We aimed in this study to explore the possible protective effects of cilostazol against CP-induced ovarian damage in female rats.Methods: Cilostazol (10 mg/kg/day) was administered orally for 10 days in presence and absence of CP (150 mg/kg IP single dose) treatment. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-Müllerian hormone (AMH) levels were determined. Ovarian oxidative stress parameters along with inflammatory biomarkers were measured. 3,5-Cyclic adenosine monophosphate (cAMP) ovarian level was detected. Ovarian histopathological examination and caspase-3 immunohistochemical study were evaluated.Results: CP-treated rats showed a significant increase in serum levels of FSH and LH with decreased serum E2 and AMH levels with an increase in the ovarian inflammatory and oxidative stress biomarkers besides a significant decrease in cAMP ovarian level with an evident histopathological picture of ovarian damage and a high caspase-3 immunoexpression. Cilostazol pretreatment significantly restored the distributed hormonal levels, the oxidative stress and inflammatory biomarkers to their normal levels with marked improvement in histopathological picture of ovarian damage with a significant decrease in caspase-3 immunoexpression.Conclusions: These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti-inflammatory, antioxidant, and anti-apoptotic properties.