Expression pattern alterations of syndecans and glypican-1 in normal and pathological trophoblast.

Syndecans (syn-1, -2, -3, -4) and glypican-1 are proteoglycans expressed during development in association with changes in tissue organization and differentiation. They participate in the modulation of growth factor actions and in cell-cell and cell-matrix adhesion. The expression of syn-1, -2, -3, -4, and glypican-1 has been studied in normal human placenta and in gestational trophoblastic disease such as hydatidiform mole, invasive mole, and choriocarcinoma, using immunohistochemistry and western blots. Syndecan-3 was not expressed in normal or pathological tissues. During normal gestation, the other proteoglycans showed a specific staining pattern, which for some was modified during pregnancy. For instance, syn-1 was only expressed in syncytiotrophoblast; syn-4 was mainly localized in the villous and extravillous cytotrophoblast in the first trimester, whereas at term it was expressed in the syncytiotrophoblast. The most striking results are the altered expression patterns of syndecans and glypican-1 in pathological tissues. These proteoglycans showed a progressive decrease of immunostaining related to the increase of severity of trophoblastic disease, in particular in invasive mole and choriocarcinoma. In addition, dysregulation in the localization of the expression patterns was observed for syn-2 and -4. Because changes in syndecan expression enable cells to become more or less responsive to their micro-environment, the down-regulation and/or dysregulation of syndecans in relation to the degree of severity of trophoblastic diseases provides new insights into the progression of these pathologies.

Heparan sulfate proteoglycans. Essential co-factors in receptor-mediated processes with relevance to the biology of the vascular wall.

Heparan sulfate (HS), a mixed bag of complex, heterogeneous and highly charged polysaccharides, is an essential co-factor in a large number of receptor-ligand interactions and cellular pathways. These co-factor functions depend on the binding-interactions of the HS chains with the ligand or receptor, or both. These binding interactions and the ensuing functional effects often depend on defined carbohydrate sequences within the HS chains, whereby the required sequences are not always represented within all natural forms of the polysaccharide. The proteins that are substituted with HS resort from a limited number of protein families, with different cellular, subcellular and supramolecular associations, and show differential activities in functional assays. It is likely that the natural co-factor functions of the HS proteoglycans depend on glycan-protein and protein-protein interactions that are subject to modulation, both at the glycan and protein levels.

Preimplantation diagnosis of aneuploidy using fluorescent in-situ hybridization: evaluation using a chromosome 18-specific probe.

Fluorescent detection of in-situ hybridization (FISH) with a chromosome 18-specific probe (P5041 B.5 D18Z1) has been used to assess the use of this method for preimplantation diagnosis of aneuploidy. Interphase nuclei (n = 802) have been analysed from 59 normally fertilized embryos developing in vitro at the normal rate between days 2 and 7 postinsemination. The efficiency of hybridization in control cells, as assessed by the proportion with two signals in normal female lymphocytes was 88.9% (n = 353) and with three signals in a trisomic (48,XXX+18) fibroblast cell line 74.0% (n = 290). Fifty-four of the human embryos were considered to be diploid on the basis that the majority of nuclei had two signals. Some nuclei in these embryos had one or no signal, especially on day 2, and tetraploid nuclei were also widespread. Among the remaining five embryos, one 5-cell embryo on day 2 had three hybridization signals in 4/5 nuclei and was trisomic for chromosome 18, one 4-cell embryo on day 2 had only one signal in 4/4 nuclei and was monosomic, and the three other embryos were aneuploid mosaics and/or had multi-nucleated blastomeres. Analysis of the incidence of interphase nuclei with more or less than the diploid number of hybridization signals indicates that more than a single nucleus will be necessary for accurate preimplantation diagnosis of aneuploidy.

Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterography.

The effect of a potent, subcutaneously injected gonadotropin-releasing hormone (GnRH analog) (Buserelin, Hoechst, Frankfurt/Main West Germany) on the size of uterine leiomyomas and the uterine cavity area was studied in a group of 20 women. In all patients except 1, the uterine cavity area calculated by hysterosalpingography was decreased, with an average decrease of 35% (from 12.0 +/- 5.4 cm2 to 7.8 +/- 3.3 cm2) by 8 weeks of therapy. Significant decrease was observed in the group of women with initial uterine cavity area greater than 10 cm2. In patients with very large submucous fibroids, myomectomy by hysteroscopy and neodymium:YAG laser was easily performed. Rapid relief of symptoms such as menometrorrhagia permits the restoration of a normal hemoglobin concentration. In conclusion, use of GnRH analog represents an adjunct for preoperative reduction of tumor size and may permit surgical treatment by hysteroscopy.

[The beneficial effects of short-term administration of a LHRH agonist (buserelin) in in vitro fertilization]. / Effets bénéfiques de l'administration de courte durée d'un agoniste de la LHRH (buséréline) en fécondation in vitro.

We have assessed the beneficial effects of administering a short course of an agonist of LHRH (Buserelin) in vitro fertilisation. 274 cycles were treated with CC-HMG, 159 were treated with HMG alone and 253 by Buserelin-HMG. These were compared retrospectively. The use of a short course of Buserelin lowered significantly the rate of failed treated cycles (7% instead of 19% when it was used with CC-HMG and 27% when used with HMG). This made it possible to administer hCG in all cases in the programme (100% as against 69% and 89% respectively for CC-HMG and HMG without Buserelin), and increase significantly the number of oocytes that could be recovered and the number of embryos available for transfer. The overall number of pregnancies per cycle treated is significantly raised when Buserelin is used with HMG (20.4% as against 13.5% for CC-HMG and HMG). The number of pregnancies that progressed, on the other hand, was similar when the cycle was stimulated with HMG alone (10.6%) or with Buserelin-HMG (10.6%).