Oxidative stress and female infertility: the role of follicular fluid soluble receptor of advanced glycation end-products (sRAGE) in women with endometriosis.

Oxidative Stress (OS) relates to the pathophysiology of endometriosis by activation of the inflammation process in the ovary, abdomen, peritoneum and endometrium. Advanced Glycation end-products (AGEs) cause oxidative damage to the follicles of the ovary. This study aims to investigate the correlation of follicular fluid soluble receptor of AGEs (FF sRAGE) with fertility-related parameters in infertile women with endometriosis. From January 2012 to July 2015 twenty-four women diagnosed with mild to moderate endometriosis aged 28-38 years underwent assisted reproduction. sRAGE levels measured in FF were related to lifestyle factors, sociodemographic characteristics, gynaecological and obstetric parameters, hormonal status and fertilization. sRAGE was inversely associated with BMI (r = -0.503, p = 0.012). No significant association of sRAGE with age (p = 0.714) or alcohol consumption (p = 0.882) was found. Pearson's r correlation coefficient revealed that sRAGE was positively associated with serum AMH (r = 0.518, p = 0.009), FF AMH (r = 0.630, p = 0.001), number of follicles >15mm (r = 0.601, p = 0.002), total number of follicles aspirated (r = 0.698, p < 0.001), total number of MII oocytes obtained, (r = 0.757, p < 0.001) and the number of embryos with good embryo scoring (suitable for ET) (r = 0.522, p = 0.009). It seems that measurement of FF RAGE might be a useful predictive marker for IVF success in infertile women with endometriosis undergoing assisted reproduction.

Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta.

Studies in mice have suggested that the placenta is protected from immune rejection by maternal T cells by means of localised indoleamine 2,3-dioxygenase dependent depletion of tryptophan. To determine whether such mechanisms might operate in the human placenta, we have studied the physiological importance of human placental indoleamine 2,3-dioxygenase immunohistochemically and functionally. Indoleamine 2,3-dioxygenase is detectable immunohistochemically from day 6 human blastocysts and thereafter throughout pregnancy in syncytiotrophoblasts, extravillous cytotrophoblasts and macrophages in the villous stroma and in the fetal membranes. Interferon-gamma added to villous explants markedly stimulates indoleamine 2,3-dioxygenase protein expression in macrophages. Indoleamine 2,3-dioxygenase-mediated tryptophan degradation in the first trimester villous and decidual tissue explants is stimulated by interferon-gamma and inhibited by 1-methyl-tryptophan (an inhibitor of indoleamine 2,3-dioxygenase). Peripheral blood mononuclear cell proliferation is controlled by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. These results suggest the cellular basis of a mechanism present at the human maternal-fetal interface involved in regulating the maternal immune response to conceptus.

An in-vitro model for stromal invasion during implantation of the human blastocyst.

BACKGROUND: Implantation failure is likely to be a major cause of infertility. Studies in mice have identified a number of molecules that are involved in implantation, but the mechanisms of implantation in the human remain unclear, largely due to the lack of models for implantation in the human that provide functional information. METHODS: Human hatched blastocysts were co-cultured with human endometrial stromal cell monolayers. Time-lapse photography of implanting blastocysts, immunostaining for cytokeratin and actin, and measurement of hCG secreted into the culture supernatants were performed. RESULTS: Blastocysts attached to and implanted into the stromal cell layer. Trophoblast outgrowth onto, and invasion into, the stromal cell layer occurred largely at two opposite poles, the orientation of which was aligned to that of the stromal cell fibroblasts. High-resolution image analysis demonstrated that the trophoblast completely penetrated the stromal cell layer. Immunostaining of whole-mounts of implantation sites revealed distinctive actin and cytokeratin-positive anchoring structures adjacent to the basal surface of the trophoblast. Blastocysts implanting into stromal cells secreted higher levels of hCG compared with those cultured on plastic. CONCLUSIONS: A robust model for the study of mechanisms of implantation of the human embryo into the endometrial stroma has been established.

Heparin-binding epidermal growth factor and its receptor ErbB4 mediate implantation of the human blastocyst.

The mechanisms that mediate implantation of the human embryo remain poorly understood and represent a fundamental problem in reproductive biology. Candidate molecules that mediate and facilitate implantation have been identified in animal studies, and include heparin binding epidermal growth factor. Here we demonstrate a potential function for the transmembrane form of heparin-binding epidermal growth factor in mediating blastocyst attachment to the endometrium, in two different novel in vitro models for human implantation. Furthermore, we demonstrate specific localisation of the heparin-binding epidermal growth factor receptor ErbB4, on the surface of the trophectoderm in peri-implantation human blastocysts. Our data lead the way for further dissection of the molecular mechanisms of implantation of the human embryo, and have implications for infertility, in vitro fertilization and contraception.