No abstract

The human endometrium is a fertility-determining tissue and a target of steroid hormones' action. Endocrine disruptors (EDs) can exert adverse effects on the physiological function of the decidua at the maternal-fetal interface. We examined the potential effects of an ED, bisphenol A (BPA), on endometrial maturation/decidualization, receptivity, and secretion of decidual factors (biomarkers). In vitro decidualized, endometrial stromal cells from six hysterectomy specimens were treated with 1 pM-1 mM of BPA, for 24 h and assessed for cell viability and proliferation. Three non-toxic concentrations of BPA (1 mM, 1 nM, and 1 pM) were selected to study its influence on secretion of cell decidualization biomarkers (IGF-binding protein and decidual prolactin (dPRL)), macrophage migration inhibitory factor (MIF) secretion, and hormone receptors' expression (estrogen receptors (ERa and ERb); progesterone receptors (PRA and PRB); and human chorionic gonadotropin (hCG)/LH receptor (LH-R)). The results showed a decrease in cell viability (P!0.001) in response to BPA at the level of 1 mM. At the non-toxic concentrations used, BPA perturbed the expression of ERa, ERb, PRA, PRB, and hCG/LH-R (P!0.05). Furthermore, 1 mM of BPA reduced the mRNA transcription of dPRL (P!0.05). Secretion of MIF was stimulated by all BPA treatments, the lowest concentration (1 pM) being the most effective (P!0.001). The multi-targeted disruption of BPA on decidual cells, at concentrations commonly detected in the human population, raises great concern about the possible consequences of exposure to BPA on the function of decidua and thus its potential deleterious effect on pregnancy.Reproduction (2015) 150 115-125

Growth dynamics and bioactivity variation of the Mediterranean demosponges Agelas oroides and Petrosia ficiformis were investigated over 15 months at Paraggi and Colombara within the Marine Reserve of Portofino Promontory (Mediterranean Sea, Ligurian Sea, Italy). For both species, growth rates varied between individuals and were unaffected by initial sponge size. The two species showed a different trend in growth pattern: A. oroides did not vary significantly between seasons, sites and depths; in contrast, some individuals of P. ficiformis showed a seasonal pattern, shrinking during winter as water temperature decreased and growing during summer when water temperature increased. Differences in growth between the two species may result from different reproductive cycles, food availability, species‐specific thermophily and patterns of spatial competition. Moreover, spatial competition probably induced sponges to produce bioactive secondary molecules. Spatial and temporal variation of bioactivity of both species was examined for the first time by studying its effect on human neuroblastoma cells. The bioactivity of A. oroides extracts differed significantly between seasons, sites and depths, whereas the cytotoxicity of P. ficiformis differed significantly between seasons and depths (differences for sites were not determined). These results suggest the possible influence of environmental factors on bioactive metabolite biosynthesis.

Successful pregnancy involves a series of events, most of them mediated by hormones and cytokines. Estrogens, besides being important for placental growth and embryo development, have a marked effect on the immune system exerting either pro- or anti-inflammatory properties. Numerous studies suggest that estrogens directly affect cellular function, including cytokine production. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in pregnancy, particularly during the earlier stages of placentation. Since reports on mice have shown that estrogens modulate MIF, herein we investigated the effect of estrogens on human placental MIF. By using an in vitro model of first-trimester chorionic villous explants, we found that 17beta-estradiol (E(2)) was able to modulate the release of MIF in a dose-dependent manner (10(-12) vs. 10(-9) M, P < 0.05; 10(-9) vs. 10(-5) M, P < 0.05; 10(-12) vs. 10(-5) M, P < 0.001). Unlike MIF release, no significant change in tissue MIF protein or MIF mRNA was observed. We showed evidence that E(2) concentrations (10(-9) and 10(-5) M) act on placental tissue downregulating the mRNA and protein expression of the ATP-binding cassette transporter protein A1, a membrane transporter involved in MIF secretion. These findings emphasize the mutual cooperation between hormones and cytokines and suggest that increasing estrogen levels with advancing gestation may have a major role in regulating placental MIF secretion.

Abstract. Among marine sessile organisms, sponges (Porifera) are the major producers of bioactive secondary metabolites that defend them against predators and competitors and are used to interfere with the pathogenesis of many human diseases. Some of these biological active metabolites are able to influence cell survival and death, modifying the activity of several enzymes involved in these cellular processes. These natural compounds show a potential anticancer activity but the mechanism of this action is largely unknown. In this study, we investigated the effects of two Mediterranean sponges, Agelas oroides and Petrosia ficiformis on the viability of human neuroblastoma cells. Upon treatment with the methanolic extract of Petrosia ficiformis, a marked cytotoxic effect was observed at any concentration or time of exposure. In contrast, a time-and dose-dependent effect was monitored for Agelas oroides that induced the development of apoptotic features and ROS production in LAN5 cells. These events were suppressed by calpeptin or zVAD and by vitamin C suggesting that the cell death caused by Agelas oroides was calpain-and caspasedependent and of oxidative nature. Comet assay showed that this methanolic extract was not able to produce a genotoxic effect. Future studies will be applied to investigate the effect of isolated bioactive compounds from crude extract of this sponge which are potentially useful for cancer therapeutics.