1,721,031 research outputs found
Hormone-like chemicals-cytokine interaction in the human chorionic villous explants
No full textProblem: hormones and cytokines acting locally at the maternal fetal interface are believed to play a major role in establishing the immune privilege of pregnancy. Numerous studies show that environment polluting chemicals can interfere with the action of natural hormones and therefore with the secretion of cytokines. In this study we investigated the effect of para-nonylphenol (p-NP), an environmental chemical with estrogenic activity as well as 17-Estradiol (E2) on human chorionic villous explants. Specifically we investigated the role of p-NP and E2 on the secretion of MIF (Macrophage Migration Inhibitory Factor), a cytokine highly present in placental tissues mainly in the early stages of pregnancy.
Methods: chorionic villous explants from first trimester human placenta were exposed to E2 or p-NP for 48 hours and then, analysed for MIF expression and its secretion in the culture medium. The membrane transporter, ATP binding cassette transporter A1 (ABCA1) was also investigated for its activity in MIF secretion.
Results: the results showed that both, p-NP and E2, significantly reduced MIF release by reducing the expression of ABCA1. Activity of p-NP was however much more potent than that of E2 since producing the same effect at much lower concentration, 1 nM (p-NP ) vs 10 mM (E2). No changes were observed in tissue MIF protein and mRNA content for any treatment
The environmental chemical Bisphenol-A interferes with the action of 17 β-estradiol in human trophoblast
No full textProblem: normal placental development is a fundamental process for pregnancy success and foetal health. We recently demonstrated that environment polluting chemicals can affect this process. In the present study we investigated the potential of these chemicals to interfere with the hormone-action thus, acting as endocrine disruptors. Specifically we studied the effect of bisphenol-A (BPA), an estrogen-like chemical largely used in polycarbonate plastics and epoxy resins.
Methods: trophoblast-like BeWo cell lines and primary cultures of chorionic villous explants from human placenta were exposed to 17 β-estradiol (E2) and BPA alone or to their combination for 24, 48 and 72 hours. Cells and tissues were analyzed for human beta-Chorionic Gonadotropin, β-hCG production.
Results: the results showed that BPA interferes with the action of the endogenous hormone E2 mainly reducing β-hCG secretion at E2 concentrations ranging from 1 nM - 1 pM corresponding to those occurring in the maternal blood in the early stages of pregnancy.
Conclusions: these findings highlight marked effects of BPA on trophoblast cell endocrine function and raise concern about the negative, potential effects on mammalian females during early pregnancy
Role of Macrophage Migration Inhibitory factor (MIF) on trophoblast growth and proliferation
No full textHormone and cytokine interaction in human trophoblast cells
No full textBlastocyst implantation and maintenance of pregnancy involve a series of events involving endocrine and paracrine factors. In particular, hormones and cytokines appear to be very important in creating the environment essential for placenta establishment.
In this study we investigated the effect of 17β-Estradiol (E2) on the secretion of the Macrophage Migration Inhibitory Factor (MIF), a pro-inflammatory cytokine highly involved in the early stages of pregnancy. By using the HTR8/SVneo cells we performed dose-response experiments with E2 concentrations ranging from 10-15 to 10-5M. We found that 10-10 and 10-13M E2 were the highest and the lowest concentrations having significant effect respectively reducing and increasing MIF levels in the culture media. Treatment with ER antagonists ICI 182 780 restored MIF levels in E2-treated samples to those of controls. These findings support interaction between hormones and cytokines in human trophoblast cells and show that MIF release is hormone receptor-dependent
Prenatal Nutrition Containing Bisphenol A Affects Placenta Glucose Transfer: Evidence in Rats and Human Trophoblast
Full text linkThis work aims to clarify the effect of dietary supplementation with Bisphenol A (BPA), a chemical widely present in beverage and food containers, on placental glucose transfer and pregnancy outcome. The study was performed on female Sprague Dawley rats fed with a diet containing BPA (2.5, 25 or 250 μg/Kg/day) for a period of a month (virgin state) plus 20 days during pregnancy. Western blot analysis and immunohistochemistry were performed in placental tissues for glucose type 1 transporter (GLUT1). Furthermore, human trophoblast, HTR8-SV/neo cells, were used to evaluate the effect of BPA on glucose transport and uptake. Studies in rats showed that food supplementation with BPA, produces a higher fetal weight (FW) to placenta weight (PW) ratio at the lowest BPA concentration. Such low concentrations also reduced maternal weight gain in late pregnancy and up-regulated placental expression of GLUT1. Treatment of HTR8-SV/neo with the non-toxic dose of 1 nM BPA confirmed up-regulation of GLUT1 expression and revealed higher activity of the transporter with an increase in glucose uptake and GLUT1 membrane translocation. Overall, these results indicate that prenatal exposure to BPA affects pregnancy and fetal growth producing changes in the placental nutrients-glucose transfer
The macrophage migration inhibitory factor (MIF) is a regulator of trophoblast growth and differentiation
No full textInduction of placental macrophage migration inhibitory factor (MIF) by low oxygen environment
No full textInhibitions of mTORC1 and 4EBP-1 are key events orchestrated by Rottlerin in SK-Mel-28 cell killing
No full textEarlier studies demonstrated that Rottlerin exerts a time- and dose-dependent antiproliferative effect on SK-Mel-28 melanoma cells during 24 h of treatment, but cytotoxicity due to cell death began only after a 48 h exposure. In the current study, in order to identify the type of cell death in this cell line, which is notoriously refractory to most anticancer therapies, and to clarify the underlying mechanisms of this delayed outcome, we searched for apoptotic, necrotic/necroptotic and autophagic traits in Rottlerin-exposed cells. Although SK-Mel-28 cells are both apoptosis and autophagy competent, Western blotting analysis, caspase activity assay, nuclear imaging and the effects of autophagy, apoptosis and necroptosis inhibitors, indicated that Rottlerin cytotoxicity was due to none of the aforementioned death mechanisms. Nevertheless, in growth arrested cells, the death did occur after a prolonged treatment and most likely ensued from the observed blockage of protein synthesis that reached levels expected to be incompatible with cell survival. From a mechanistic point of view, we ascribed this effect to the documented inhibition of mTORC1 activity; mTORC1 inhibition on the one hand led to a not deadly, rather protective autophagic response but, on the other hand caused a near complete arrest of protein synthesis. Interestingly, no cytotoxicity was found towards normal skin fibroblasts, which only resulted mildly growth arrested by the drug
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