[Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases]. / Rôle potentiel du facteur angiogénique «EG-VEGF¼ dans les maladies gestationnelles trophoblastiques.

Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter.

Impact of nitrate intake in drinking water on the thyroid gland activity in male rat.

The purpose of this study was to determine the effects of nitrate on both the activity of the thyroid gland and other biological parameters. After 5-month treatment, nitrate 150 and 500 mg/l induced a significant decrease in the serum level of thyroid hormone T3. For T4, the 500 mg/l dose only reduced its plasma level. On the other hand, nitrate induced a dose-dependent increase in the weight of the thyroid gland. The histological study of the thyroid gland shows vacuolisation and an increase in the size of the follicles accompanied by a flatness of follicular epithelium with nitrate 150 and 500 mg/l. We concluded that the presence of high concentrations of nitrate in drinking water influence the growth, induce morpho-functional modifications of the thyroid gland and might be considered as a goitrigenic factor.

Fetal target organs of graft-versus-host reaction induced in utero by injection of maternal cells in a pig model.

The target organs of graft-versus-host reaction (GVHR) in adult or neonates are the site of multifocal lymphocytic infiltrates. GVHR can also be acquired in utero by maternal cells crossing the placenta, but the fetal target organs are unknown. The aim of this study was to determine these target fetal organs. The distribution pathway of infused labeled lymphocytes within cryostat sections of fetal organs was analyzed, and fetal target organs of infused lymphocytes were investigated in both isogenic and semiallogenic situations. Isogenic cells were observed in less organs and semiallogenic cells were localized in a more restricted number of organs than isogenic cells. Furthermore, the liver, the thyroid, and the spleen were the fetal target organs in the two studied gestations. GALT, thymus, and kidney were also lymphocyte targets in isogenic gestation. In conclusion, isogenic cells induced GVHR in more fetal organs than semiallogenic cells.

[Factors limiting in utero lymphocyte transplantation and cell therapy]. / Facteurs limitant la transplantation des lymphocytes in utero et thérapie cellulaire.

To evaluate factors of cell transplantation in utero in human, we have injected into rat fetuses of varied stage (n=61) several doses of non labeling lymphocytes mixed with FITC labeled latex beads. The ratio of fetal death and the histopathological effect longer after birth were assessed. Our results showed that the elevated fetal death ratio were observed after the injections of a high doses in young fetuses. Low doses provoked the same effect when injected to old fetuses. In living fetuses, histopathological lesions mimicking a graft versus host reaction were noticed throughout several organes six week after birth. We concluded that lymphocyte transplantation in utero depends on the dose of injected cells and stage of fetal development.

Effect of in utero infusion route on lymphocyte distribution in fetal rat tissues.

Infusion of cells into the fetus is a new form of intrauterine therapy for several genetic disorders. The effect of in utero infusion routes on labelled lymphocyte distribution in fetal rat organs was investigated. Fetuses, 14-16 days of gestation, were infused in utero with a Hoechst 33342 (bis-benzamide) labelled lymphocyte and FITC-labelled polystyrene bead mixture via four routes: intraperitoneal, intraplacental, intra-amniotic, and intravenous. The distribution within tissues was evaluated in frozen sections of placenta and fetal organs. Our results suggest that among the four routes tested, the intravenous route offered the possibility to reach easily fetal organs without any cell loss and yielded higher cell and bead concentrations in fetal organs, especially in the liver and in the kidney. In conclusion, the intravenous route seems to be appropriate for hematopoietic cell transplantation in the developing fetus.

Inhibitory effect of 17 beta-estradiol on thymocyte proliferation and metabolic activity in young rats.

Proliferation of 21-day-old rat thymus lymphocytes has been assessed after 7 daily injections of 17 beta-estradiol (E2). Two methods were used: 1) image cytometry of cell nuclei using the SAMBA 200 image processor, and 2) cell culture making it possible to design cell proliferation assay, mitochondrial activity evaluation and measurement of IL2 activity. Using image cytometry, we found a significant decrease in the proliferation index at the dose of 100 micrograms of E2 per day. When 200 micrograms and 400 micrograms per day were given, this decrease reached 70% of inhibition. 3H-thymidine incorporation was significantly reduced in cell culture even after 5 micrograms of E2 per day. On the other hand, with either 5 micrograms or 50 micrograms of E2, a significant increase of IL2 was found in the supernatant.

[Effect of bromocriptine and bromocriptine combined with prolactin on the proliferation of thymocytes in young rats]. / Action de la bromocryptine et de la bromocryptine associée à la prolactine sur la prolifération des thymocytes de jeune rat.

The effects of bromocriptine and bromocriptine associated to prolactin have been investigated on young rat thymocytes after sensitization with T-cell antigen SRBC using a quantitative nucleus image analysis (Samba 200). Bromocriptine alone induces an inhibition of lymphocyte proliferation, a chromatin condensation and enhances cell differentiation. These effects are reversed by prolactin, which therefore acts on lymphocytes before they leave the thymus.

Image analysis of cell proliferation in rat thymus throughout development.

A System for Analytical Microscopy in Biological Applications (SAMBA 200) was used to digitize, process and statistically analyze the cell proliferation of rat lymphoid cells throughout thymus development. This cytometric study shows that lymphoid cell proliferation starts in 14-day-old embryos, remains high throughout embryogenesis with a maximum around day 18, decreases after birth then rises again in 21-day-old rats, after which proliferation decreases gradually with age, this decrease appears even before the onset of the sexual maturation, and is very marked in 2-year-old animals. Image cytometry analysis makes it possible to distinguish 5 lymphoid cell subpopulations (lymphoid stem-cells, lymphoblasts, large lymphocytes, medium lymphocytes, and small lymphocytes), and to discriminate in each cycling and non-cycling cells. The S-fraction of the lymphoid stem-cells decreases in 16-day-old rats, while the S-fraction of the lymphoblasts increases rapidly during the embryonic period. The large lymphocytes show the highest S-fraction at the stage E18, while the medium lymphocytes show the more stable S-fraction. The S-fraction variation for small lymphocytes can be divided into three periods: 1. up to E16 (S-fraction increases rapidly); 2. between newborn and 21 days (S-fraction increases slowly and irregularly); 3. after 21 days (S-fraction decreases progressively).