In vivo assessment of the early uteroplacental circulation.
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Biomedical subjects
Publications and source records attributed to O Genbacev.
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Implantation is the process that leads from blastocyst attachment to its embedding in the uterine wall. It is widely believed that failure of implantation is a common cause of pregnancy loss. Toxic agents can interfere directly with the process of implantation and therefore may account for unexplained implantation failures. Our knowledge of human implantation remains limited, mainly due to the lack of adequate experimental models. Studies of mechanisms underlying implantation in humans are by nature and for ethical reasons restricted to in vitro models. The aim of this review is to provide a critical evaluation of various in vitro models of implantation in humans, as well as essential background knowledge required for application of these models to the assessment of peri-implantation toxicity. Particular attention has been devoted to cell-cell and cell-matrix interactions as possible endpoints in the screening of toxic agents.
Adequate acrosome reaction is one of the essential events that has to occur in successful mammalian fertilization. The purpose of the present study was to assess the acrosome reaction in human spermatozoa by means of iodine-labelled lectins concanavalin A and peanut agglutinin ([125I]Con A and [125I]PNA). Six sperm samples in the control (fertile) group were compared with 24 samples obtained from infertile patients. The acrosome reaction in both groups was induced in vitro by adding follicular fluid. Iodine-labelled lectins were bound to the sperm surface, and alteration in the binding capacity for [125I]PNA and [125I]Con A after induced acrosomal reaction was the main parameter for the prediction of acrosome reaction and fertilizing ability. It is hoped that with the availability of this test, in-vivo data may be accumulated.
Recently it has been demonstrated that human placental tissue is a source of transforming growth factor-beta (TGF-beta) and that it expresses high TGF-beta mRNA activity. For a better understanding of its in vivo function, it was necessary to determine the site of TGF-beta synthesis in placenta. We have demonstrated that TGF-beta immunoreactivity is present in the cytoplasm of syncytiotrophoblast cells in both early and term placenta. The most intense staining was, however, observed in the first trimester trophoblast syncytial sprouts known to be an early stage in the development of placental villi. These results suggest the involvement of TGF-beta in the paracrine regulation of trophoblast-endometrial interaction.
Congenital absence of both vas deferens accounts for approximately 10% of cases of obstructive azoospermia. The purpose of the present study was to develop a treatment protocol for a group of azoospermic patients using surgical implantation of alloplastic spermatocoele to enable repeated sperm cell aspiration. Nine patients with congenital absence of both vas deferens, two with obstructed and one with destroyed vas, underwent surgery for the implantation of an alloplastic spermatocoele. In 10 of the 12 patients, vital spermatozoa were recovered from the aspirate and used for intrauterine insemination of their female partners with induced ovulation, some of whom then conceived.
Opiate synthesis by human placental cells and the presence of kappa-type opiate binding sites in the syncytiotrophoblast brush border membrane may indicate the possible role of morphine-like substances in the autocrine regulation of trophoblast cell metabolism. This study was undertaken to examine the in vitro effect of morphine on hCG (human chorionic gonadotrophin) and hPL (human placental lactogen) release by 1st and 3rd trimester placental tissue explants. The results have shown that morphine (100 nM) significantly stimulated hCG secretion by 6-8 weeks old trophoblast and was without effect on hPL. Hormone secretion by term placental tissue explants was unaffected by morphine treatment. Based on these results we assume that opiates may have a role in the local (autocrine and/or paracrine) regulation of hCG secretion in early gestation.
21 patients with chronic cystitis due to irradiation therapy for carcinoma of the cervix had symptomatic and cystoscopic improvement from instillations of early placental extract in saline. There was a statistically significant difference between these patients and a control group.
Phosphorylation of cytosol proteins in placental tissue of different gestational age has been studied. Cytosol protein phosphorylation was stimulated by exogenous cAMP only in term placentae and remained unchanged in first and second trimester placentae. Exogenous proteins, histone and casein, were intensively phosphorylated by cytosol kinases with maximal activities in first trimester cytosol preparations. Exogenous cAMP stimulated histone phosphorylation, but it had no effect on casein phosphorylation. On the basis of the obtained results it can be concluded that endogenous protein phosphorylation in first and second trimester placental cytosol is cAMP independent.
Serum levels of FSH, LH, prolactin, testosterone, and estradiol in 46 infertile men with hyperprolactinemia were compared with the same in 50 infertile and 30 fertile men with normal serum prolactin levels. Serum FSH levels in hyperprolactinemic men were significantly higher than in the other groups, indicating disturbance of spermatogenic process among those men. Significantly raised serum LH levels were in infertile men with serum prolactin over 1000 U/liter. All men with hyperprolactinemia had significantly lower serum testosterone levels than other infertile and fertile men. Although serum testosterone was not under the lower limit of normal range and high LH levels demonstrated disturbance of Leydig cell function in hyperprolactinemic infertile men, serum estradiol levels were not different among investigated groups. Azoospermic men with raised serum prolactin had higher serum FSH and LH levels than oligospermic men with hyperprolactinemia. These data demonstrated disturbance in hypothalamopituitary-testicular axis in infertile men with hyperprolactinemia. Further studies of prolactin in males with reproductive failure could probably clear this problem.
Beta-sympathomimetic drugs are clinically widely used in the management of threatened premature labour. The existence of beta-adrenergic receptors has been demonstrated in the human placenta and, as the stimulation of beta-adrenoreceptors is known to be mediated by cAMP, the purpose of this study was to compare the effect of Ritodrinum on cAMP concentration in placentas of different gestational age. The in vitro treatment with Ritodrinum induced a five fold increase in cAMP concentration in 6-8 week old placenta, three fold increase in midgestation, but was without effect in term placenta. This result suggest that beta-mimetics in pharmacological concentrations could modulate trophoblast cell activity through the cAMP-dependent system during the first half of gestation.
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Lung and liver tissue slices from fetuses aborted at 20 weeks gestation were incubated for 8 hours in MEM Eagle's medium containing PRL (85 ng/ml). Protein synthesis and AFP concentrations were measured in the tissue and the incubation medium. The obtained results showed that protein synthesis was reduced by 30% in the lung and by 55% in the liver tissue slices after PRL treatment in vitro. The AFP concentration remained almost unchanged in the lung and was reduced in the liver. Direct evidence that AFP is not synthesized by human fetal lung of 20 weeks gestation was provided from experiments with puromycin. In spite of the strong inhibition of protein synthesis in both fetal lung and liver, AFP concentration was reduced only in liver and remained unchanged in the lung.
High serum prolactin was detected in 15 out of 110 azoospermic men (13%). Patients underwent hormone assays, sellar radiography, and testicular biopsy (histological and meiotic analyses). Three patients, with most elevated serum prolactin level, had spermatogenic arrest. Nine patients showed no spermatogenic activity on histological and meiotic preparations. Three patients had normal and decreased spermatogenesis and normal meiotic divisions. The patients with spermatogenic arrest and with preserved spermatogenic process were treated with bromocriptine. Spermatogram in two patients with preserved spermatogenic process was ascertained to nearly normal range, after the treatment. There was no specific histologic or meiotic lesion in azoospermic men.
The postovulatory effects of pharmacological doses of LH-RH on progesterone and LH plasma concentrations have been demonstrated. LH-RH injected on the 16th and 18th day of the menstrual cycle induces the discharge of LH; the second application results in a weaker discharge, indicating that the pituitary stores are exhausted. A LH-RH injection induces a decrease of the plasma progesterone concentration which becomes evident after a delay of 26 hours. A statistically significant correlation between LH and progesterone plasma concentrations was obtained 26 h after the administration of LH-RH.
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Biochemical and morphologic studies have shown that proteins and carbohydrate-protein complexes, in addition to phospholipids, are present in the alveolar surface layer. For this reason the study of lung protein synthesis in parallel with phospholipid biosynthesis and its regulation is of interest. The data obtained show that from 16 to 24 weeks' of gestation the human fetal lung rapidly incorporated 14C-leucine into proteins from the particulate fraction and 105,000 x g tissue supernatant fraction. The distribution of radioactivity between protein fractions after gel filtration on Sephadex G-200 revealed three major peaks of radioactivity. According to our results the protein, detected at the site of the 7S peak of normal serum, was synthesized in vitro by human lung tissue, as was a more rapidly labeled 19S protein which was released into the incubation medium. The addition of prolactin and cortisone to the incubation medium led to a dose-dependent inhibition of total protein synthesis by the human fetal lung in vitro. The significant decrease in 14C-leucine incorporation was noticed in proteins eluted from the Sephadex G-200 column in fractions corresponding to the 19S and 7S peaks of normal human sera.