Biomedical subjects

K Handschuh

Publications and source records attributed to K Handschuh.

12 recordsLinked to original sources

PubMed2006

PPARs and the placenta.

The discovery of the peroxisome proliferator-activated receptors (PPARs) in 1990s provided new insights in understanding the mechanisms involved in the control of energy homeostasis and in cell differentiation, proliferation, apoptosis and the inflammatory process. The PPARs became thus an exciting therapeutic target for diabetes, metabolic syndrome, atherosclerosis, and cancer. Unexpectedly, genetic studies performed in mice established that PPARgamma are essential for placental development. After a brief description of structural and functional features of PPARs, we will summarize in this review the most recent results concerning expression and the role of PPARs in placenta and of PPARgamma in human trophoblastic cells in particular.

Animals↗

PubMed2006

Expression of the fusogenic HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted to villous cytotrophoblastic cells.

Recently, the expression of a human endogenous retrovirus HERV-FRD, able to encode a fusogenic envelope protein (syncytin 2), has been observed in human placenta. The aim of the present study was to localize the expression of syncytin 2 in first trimester placenta. In addition, we investigated the presence of HERV-FRD transcripts during the in vitro differentiation of isolated villous and extravillous trophoblastic cells from first trimester chorionic villi. Using a monoclonal antibody specifically raised against the HERV-FRD Env protein, syncytin 2 was immunolocalized only in the villous trophoblast of the chorionic villi, at the level of cytotrophoblastic cells. Interestingly, immunostaining was not observed in all cells but only in some of them, and was detected, more frequently, at the membrane level at the interface between the cytotrophoblastic cells and syncytiotrophoblast. Labeling was observed neither in the syncytiotrophoblast nor in the mesenchymal core of the villi nor in the extravillous trophoblast. In vitro detection of HERV-FRD transcripts was restricted to villous trophoblastic cells and decreased significantly with time in culture. These results suggest that syncytin 2 might play a role in human trophoblastic cell fusion.

Cells, Cultured↗

PubMed2006

Human chorionic gonadotropin expression in human trophoblasts from early placenta: comparative study between villous and extravillous trophoblastic cells.

Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse to form the syncytiotrophoblast (ST) involved in placental exchanges and endocrine function. It is established that hCG is produced and secreted by the ST into the maternal compartment where it plays a key endocrine role and stimulates ST formation in an autocrine manner. Herein, we investigated hCG expression in early placentas by immunohistochemistry using different antibodies. We then compared hCG secretion by primary cultures of VCT and EVCT isolated from the same first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all along their invasive differentiating pathway except in cells near the stromal core of the proximal column. hCG expression was confirmed in vitro by immunocytochemistry and hCG secretion quantified in cell supernatants. Interestingly, whereas hCG secretion increased during VCT differentiation into ST (from 60 to 350UI/L/microg DNA), EVCT secretion remained constant and at a high level during the same culture period (160UI/L/microg DNA). Our data demonstrated that in addition to the ST, invasive EVCT also expressed and secreted high levels of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT origin.

Animals↗

PubMed2006

Modulation of PAPP-A expression by PPARgamma in human first trimester trophoblast.

Pregnancy-associated plasma protein-A (PAPP-A) is a metzincin metalloproteinase that cleaves the insulin-like growth factor (IGF)-dependent binding protein-4 and increases in maternal serum during pregnancy. In human placenta PAPP-A is expressed both in villous cytotrophoblasts (VCT) that cover the chorionic villi and in extravillous cytotrophoblasts (EVCT) of the anchoring villi. Due to the key role of PPARgamma in human trophoblast differentiation such as syncytiotrophoblast formation and EVCT invasion, we studied the effect of PPARgamma activation on PAPP-A expression using our in vitro model of EVCT and VCT primary cultures isolated from the same first trimester chorionic villi. First, we demonstrated that invasive EVCT expressed and secreted 10 times more PAPP-A than VCT did. Then, we showed that activation of PPARgamma inhibited PAPP-A gene expression and secretion in EVCT, whereas it had no effect in VCT. Since we have previously shown that PPARgamma agonist inhibits EVCT invasion in vitro, we suggest that PPARgamma-mediated inhibition of PAPP-A might decrease the amount of bioactive IGFII, a factor known to promote trophoblast invasion.

Chorionic Villi↗

PubMed2005

Expression of HERV-W Env glycoprotein (syncytin) in the extravillous trophoblast of first trimester human placenta.

Although the extravillous trophoblastic invasion has a critical role in human placental development, nothing is known about HERV-W expression in the extravillous phenotype. The aim of the present study was to localize in first trimester placenta the expression of HERV-W Env glycoprotein and its receptor all along the differentiation pathway of the extravillous phenotype. In addition using an in vitro model of extravillous cytotrophoblastic cell isolation and invasion we investigated the presence of HERV-W transcripts and envelope glycoprotein in cultured extravillous trophoblastic cells. Using monoclonal and polyclonal antibodies, the glycoprotein was immunolocalized in all the cell types of the extravillous phenotype lineage: cytotrophoblastic cells of the column, interstitial extravillous trophoblastic cells, multinucleated giant cells and endovascular trophoblast. Furthermore, using a polyclonal antibody, the D mammalian virus receptor was also localized in the various extravillous trophoblastic phenotypes. In addition, the presence of HERV-W transcripts and protein was demonstrated in cultured extravillous trophoblastic cells. HERV-W Env glycoprotein expressed in villous and extravillous trophoblast can be considered as a specific marker of the human trophoblast.

Adult↗

PubMed1986

[Initial experiences with interstitial brachycurietherapy (low dose rate I-125 seeds in carrier/vicryl and high dose rate Ir-192 afterloading system) in the palliative treatment of head and neck tumors].

The local control rates for previously irradiated recurrent tumours of the head and neck is dose dependent. High dose percutaneous irradiation alone is associated with a high complication rate. On the other hand it is possible to apply high local doses by interstitial irradiation, whilst sparing the surrounding tissue. In the last 2 years we have used Iodine 125-seeds in carrier (Vicryl) and a high dose rate Iridium 192-source for the afterloading technique. Our first experiences with 12 patients show reasonable palliation, but not effect on survival.

Brachytherapy↗

PubMed1970