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Biomedical subjects

R de Hertogh

Publications and source records attributed to R de Hertogh.

17 recordsLinked to original sources
PubMed2001

Control of trophectoderm differentiation by inner cell mass-derived fibroblast growth factor-4 in mouse blastocysts and corrective effect of FGF-4 on high glucose-induced trophoblast disruption.

Previous studies have suggested that fibroblast growth factor-4 (FGF-4) may be a paracrine signal used by inner cell mass (ICM) cells to maintain adjacent trophectoderm (TE) cells in an undifferentiated state. In the present work, immunocytochemical analysis of mouse blastocysts confirmed that FGF-4 was predominantly detected in the ICM before and after spreading over a fibronectin-coated culture substrate. Addition of human recombinant FGF-4 did not influence morphological progression, cell allocation and proliferation in ICM and TE lineages or mitosis and karyorhexis frequencies during blastocyst expansion. Addition of FGF-4 to outgrowing blastocysts, in contrast, induced a significant decrease in the surface of the trophoblast outgrowths formed by the TE cells and in the proportion of giant trophoblasts per outgrowth. The fact that blastocysts display excessive trophoblast expansion and spreading over their culture substrate upon pre-exposure to high concentrations of glucose in vitro was used to further assess the regulatory effect of FGF-4. Addition of FGF-4 was indeed found to fully neutralize the disruptive impact of high glucose on trophoblast outgrowths. Altogether, our data indicate that ICM-derived FGF-4 participates actively in the regulation of trophoblast development.

Animals↗
PubMed1994

Down regulation of the angiotensin II receptor subtype AT2 in human myometrium during pregnancy.

Samples of human myometrium have been collected during pregnancy and from non-pregnant women. Binding studies revealed the presence of a 50-fold higher density of angiotensin II AT2 receptor in the non-pregnant state than during gestation. Low levels of the AT1 receptor subtype (approx. 20 fmol/mg protein) were detected in both pregnant and non-pregnant myometrium. Outside pregnancy, the AT2 receptor accounted for greater than 95% of all angiotensin receptors, whereas during pregnancy the value dropped to about 40%. The down regulation of the human myometrial AT2 receptor during pregnancy may be related to the high hormonal content of the environment induced by gestation. The mechanism by which the AT2 receptor is regulated appears to be different to that of the AT1 receptor.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1991

[Angiotensin II receptors in the human placenta are type AT1].

Membrane angiotensin II receptors were measured in human placenta by means of 125I [Sar1 Ile8] All (angiotensin II antagonist) and characterized by using 2 other antagonists of angiotensin II: Dup 753 and CGP 42112A. These are specific and selective ligands which enable identification of AT1 and AT2 receptor subtypes respectively. The [Sar1 Ile8] All affinity is similar (Kd approximately 1 nmol.l-1) in the 3 different placental structures examined. However, the Bmax of villous tissues is approximately 9 times higher than that observed in chorionic plate but remains near that found in basal plate. In the central area of the placenta, mean values of 125I [Sar1 Ile8] All binding observed at a single concentration of 0.15 nmol.l-1 are 242 +/- 31 fmol/mg proteins in basal plate, 300 +/- 35 in villous tissues and 36 +/- 8 in chorionic plate. The umbilical vein and arteries respectively have 8.8 +/- 4.8 and 4.0 +/- 1.7 fmol/mg protein. The subtype analysis shows that only AT1 receptor is present in placental tissues. The Bmax values as well as those obtained by the relative measurement performed at a fixed 125I [Sar1 Ile8] All concentration of 0.15 nmol.l-1 indicate that the highest concentrations of angiotensin II receptors are found in placental villous tissues.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1991

[The value of radioimmunoassay of urinary hCG in an in vitro fertilization program].

Radio-immuno-assay estimations of urinary hCG were carried out with pharmacia Kit beta hCG Riact on 36 women who had received embryo transfers. The analysis was carried in order to try and find how and at what moment in time it is possible to diagnose very early a developing pregnancy after embryo transfer. In this work we have found that the mean level of urinary hCG was significantly higher (P less than 0.001) in women who became pregnant (group B) than in those who did not become pregnant (group A). The difference in mean hormone levels in these two groups became more marked in the following days. The time doubling of the hCG level varied between 1.21 and 3.24 days in group B. By the eighth day the level of urinary hCG was less in group B than in group A, probably due to rapid renal breakdown of hCG. In summary these results show that the level of urinary hCG estimated from the 11th day onwards after an embryo transfer repeated two or three days later makes it possible to detect early pregnancies.

Adult↗
PubMed1990

Decreased inner cell mass proportion in blastocysts from diabetic rats.

Late morulae and blastocysts were recovered from streptozocin-induced diabetic pregnant rats and individually examined for numbers of inner cell mass (ICM) cells and trophectoderm (TE) cells. Compared with embryos collected from control rats, exposure to maternal diabetes significantly decreased mean ICM cell number of blastocysts recovered on day 5 of gestation, but the TE population of these embryos remained unaffected. The mean ICM proportion was therefore significantly lower than that of control embryos. These differences were not observed between the two groups of morulae collected on day 5, suggesting that the distinctive susceptibility of the ICM was expressed after blastocyst formation. On day 6, a significant inhibitory effect of diabetes was observed on the growth of both ICM and TE cells, but because the reduction was more severe in the ICM than in the TE, the mean ICM proportion of these blastocysts was again significantly lower than in control embryos. A linear quadratic relationship was obtained between the numbers of ICM cells of individual blastocysts and their respective numbers of TE cells in each of the two experimental groups. However, the slope of the curve was slower in the diabetic group than the control group. The disturbed ICM cell growth in the blastocysts from diabetic rats was found to be associated with a significantly increased incidence of cell death predominantly located in the ICM. Because it is known that excessive reduction of the ICM is incompatible with normal embryogenesis after implantation, our results suggest that the differential sensitivity of ICM and TE cells in preimplantation blastocysts may contribute to the pattern of postimplantation defects described in diabetic pregnancies.

Animals↗
PubMed1990

[An evaluation method for the determination and monitoring of urinary HCG].

A kit of anti-beta hCG monoclonal antibodies (Pharmacia beta hCG Riact) has been tested in the assay and monitoring of urinary hCG. After several tests, the technique was found to be reproducible and specific for assay of hCG and showed good sensitivity in urine assays. Optimal sensitivity was seen in the urine pH range 5.5 and 10.00. Below 5.5 and above 10.00, its detection capacity dropped off sharply. Dilution of urine with the kit buffer gave hormonal values comparable to those of undiluted urine, but improved them substantially when the urine pH was below 5.5. It is therefore wise to dilute urine to avoid the potential risk of assay interference by urine acidity. In frozen urine, hCG concentrations tend to decrease but are not altered significantly. This recently developed method allows easy and reliable monitoring of urinary hCG for detection of unknown pregnancy in spontaneous cycles, surveillance of the state of embryos transferred during in vitro fertilization cycles, and evaluation of the efficacy of treatment of tumors secreting (beta hCG).

Adult↗
PubMed1987

Estradiol-induced progesterone receptor synthesis in normal and diabetic ovariectomized rat uterus.

Estrogen stimulation of progesterone-receptor (Prog R.) synthesis is an important parameter of the sex hormones activity at the uterine level. Experimental diabetes in the rat has been shown to perturb protein synthesis in some tissues and to reduce, under certain circumstances, estrogen and androgen activity on their respective target tissues. The present work tended to evaluate the effect of streptozotocin diabetes on estradiol (E2) stimulation of Prog. R and on Prog R. kinetics in the rat uterus. Two groups of diabetic rats were primed for three consecutive days with 5 microg. E2 s.c. (EP). One group received an acute i.p. injection of progesterone (P), 1 h before sacrifice (Inj), the other group did not (n Inj). Two other groups, not primed with E2 (nEP) were similarly injected or not with P. Four groups of non diabetic animals served as controls. Estrogen priming induced a 20-25% increase in DNA content, both in controls and in diabetics. Protein content was also increased to almost the same extent in diabetics and controls; protein concentration remained however slightly lower in cytosol of EP diabetics as compared to controls. Prog R. increased about 7-fold in cytosol and 4-5-fold in nuclei of EP control and diabetic groups. Cytosol to nuclei ratios of Prog R. decreased similarly in Inj. EP diabetics and controls, compared to the corresponding n Inj. groups. It is concluded that estrogen priming stimulated Prog R., total protein and DNA synthesis to the same extent in diabetic as in control rats Prog R. kinetics was unaltered in diabetics. This finding might be relevant to situations like early pregnancy, when Prog R. levels change rapidly and specifically in relation with the time and the site of implantation.

Animals↗
PubMed1982

Correlation between hormonal levels and ultrasound in patients with threatened abortion.

96 women with threatened abortion were monitored by repeated ultrasonic examinations. Simultaneously plasma HCG, progesterone, estradiol and estriol levels were measured. 12 patients with blighted ovum had hormonal levels in the low normal range before the 8th week and abnormal values after the 10th week. 31 patients had abnormal ultrasonic morphology and absence of fetal heart movements. In half of these patients, estradiol was low even before vaginal bleeding. When vaginal bleeding occurred, all subjects who aborted later, except 1, had at least one abnormal hormonal value. In 4 cases, fetal life signs were detected only after the 10th week; hormonal levels remained normal, confirming the presence of a viable fetus. 31 patients had normal ultrasounds despite vaginal bleeding and arrived to term. Hormonal profiles were also normal. 18 patients had normal ultrasounds and aborted in the second trimester of pregnancy. Some of them had low normal hormonal levels. Others had a secondary decrease in hormonal levels (most often estrogen levels) which, in some cases, preceded the abnormality of the ultrasounds. It is concluded that ultrasounds and hormonal measurements are complementary. Ultrasounds alone gave a correct prognosis in 78% of the cases after a single examination. Caution is advised when fetal life signs are absent and termination of pregnancy is contemplated. Hormonal measurements may then confirm or refute the unfavorable prognosis. Also, hormonal measurements may provide some insight as to the subsequent evolution of a threatened pregnancy, even in the presence of normal ultrasounds. The therapeutic prospect of this knowledge is, however, still to be defined.

Abortion, Spontaneous↗
PubMed1982

[Intravenous administration of ritodrine to pregnant insulin-dependent diabetics. Metabolic impact].

Seven diabetic patients who had been dependent on insulin before pregnancy (classes B, C, D of White) threatened to go into premature labour between the 31st and 36th week of the pregnancy. They were treated by intravenous administration of Ritodrine, the dosage varying between 100 and 400 micrograms per minute. The changes in the mother consisted in a rise in the blood glucose level which rose from 140 +/- 34 mg % to 212 +/- 56 mg % (p less than 0.01). This occurred in spite of a mean rise of 49% of insulin (p less than 0.0025) and a moderate ketonuria in two patients and a severe acido-ketosis in two further patients. In five patients there were no effects on the fetus as far as repeated observations of the fetal heart rate could detect. On the other hand, in the two mothers who developed acido-ketosis during the transfusion the fetal heart rythm showed signs of acute fetal distress, which however was temporary. Oscillations were reduced and there were late decelerations. These disappeared when the maternal metabolic state was brought back to equilibrium. 13.1 +/- 7.3 days were gained for the fetus by using tocolytic treatment, and this is considered a success. Discussion of these cases is accompanied by a complete review of the literature of the administration of beta-mimetic drugs in diabetic women. The authors point out that special precautions have to be taken and special conditions have to be fulfilled when this type of treatment is used. These consist of changes in the amounts of insulin that are given and particularly careful observation of the fetal heart rhythm before and during treatment.

Adult↗
PubMedDate not supplied

Angiotensin II and its different receptor subtypes in placenta and fetal membranes.

The recent discovery of a local renin-angiotensin system in trophoblastic tissues has raised many questions regarding its role in the physiology of normal gestation and its implications in the pathophysiology of hypertension during pregnancy. In this article, the authors first review the most interesting aspects of the chorioplacental renin-angiotensin system, dwelling on the tissue distribution of angiotensin II and its receptor subtypes in the placenta and fetal membranes of different species. The relationship between angiotensin II and other locally synthesized chorioplacental substances is also analysed and the therapeutic implications of phenomena observed in pregnancy-associated hypertension are discussed.

Angiotensin II↗
PubMedDate not supplied

Longitudinal follow-up of breast cancer patients with the tumor markers CA 549 and CA 15.3.

In order to verify the efficiency of the tumor markers CA 15.3 and CA 549 in the follow-up of breast cancer patients, it was necessary first to check the cutoff levels of each tumor marker in women with an increased age-related risk, but with no evidence of disease. From 132 serum samples in this age group, we confirmed the CA 549 cutoff level of 12.1 U/ml. However, the cutoff of CA 15.3 was 34 U/ml, which is higher than previously reported in the literature. Fifty-two breast cancer patients with or without metastases at the time of entry into the study were followed for 2 to 3 years with both tumor markers. The sensitivity, specificity and the test efficiency for the presence of metastases were analyzed with each tumor marker. Taking into account the different cutoff levels, we concluded that both tumor markers can be used independently to follow the clinical situation of patients. In several cases an increase in both tumor markers was observed before a clinical diagnosis of metastases could be made. Combination of these two tumor markers gave no more significant information about the patient's clinical situation than each tumor marker alone.

Adult↗