Proteins-markers of placental insufficiency

The proteomic analysis of amniotic fluids of women with physiological pregnancy and pregnancy, complicated by placental insufficiency has been carried out on the second and the third trimesters. The differences in protein patterns between physiological pregnancy and pregnancy complicated by placental insufficiency seen during these gestation periods include: i) the absence of peroxiredoxin 2, epidermal fatty acid binding protein, and haptoglobin in placental insufficiency; ii) appearance of several proteins absent in physiological pregnancy: hippocalcin-like protein 1, CDC37-like protein, NKG2D ligand 2 (II trimester), CDC37-like protein, NKG2D ligand 2 (III trimester). These differences in the amniotic fluid proteome, obviously, have pathogenetic importance for the development of the placental insufficiency. The revealed proteins of distinction may serve as markers of this obstetrical pathology.     

Thermoregulatory reaction in the rabbit fetuses developing under the reduced utero-placental blood flow

Rectal temperature, temperature of the brown adipose tissue, and the heart rate were studied in the rabbit foetus under intact and reduced utero-placenta blood flow in the end of the intrauterine development. With the reduced utero-placenta blood flow, bradycardia and a drop in the brown fat metabolism due, probably, to an insufficient development and functional immaturity of this tissue, were revealed.     

Tissue receptor reaction to transient anoxia in the absence of glucose

Under conditions of anoxia for 15 min and at glucose absence in the incubation medium, the frog urinary bladder receptors loose their ability to generation of spikes much quickly, than under the same conditions, but in glucose presence. Sorption of vital dye (methylene blue) by the terminals sharply decrease up to a complete their inability to be stained. After glucose is injected, this ability is partly restored. Ability of mitochondria to contrasting with usual electron microscopical contrast media is also noted to change.     

Spectral-fluorescent characteristics of rat transcortin in normal conditions and during experimental circulatory insufficiency

Spectral-fluorescent parameters of rat transcortin isolated from blood plasma of intact rats and rats with circulatory insufficiency were studied. The differences in the Schtern Folmer constants and the dissociation constants for the transcortin-corticosterone complex obtained during the protein titration by corticosterone may be due to different tryptophanyl surroundings in the molecules of the studied proteins. This may be a consequence of the conformational rearrangements of the corticosteroid-binding globulin molecules.     

Pharmacological management of an impending placental insufficiency

By means of drug administration a further decrease of the placental circulation in premature sonographic maturity of the placenta could be prevented via influencing the TXA2/PGI2 balance. Treatment of premature sonographic placental maturity with 50 mg acetylsalicylic acid (ASA) per day and three times daily 100 mg Rocornal, respectively, resulted in a significant increase of the birth weights. In a second series of experiments, three groups were treated with 50 mg/day ASA or 250 mg ASA/once per week and three times/day 100 mg Rocornal, respectively, from the 18th or 20th week of gestation to the 35th week. Subsequently, they were compared to a group of untreated controls. The birth weights of all treated groups were statistically significantly higher. The underlying mechanism is suggested to be an improved microcirculation.     

Pregnancy-associated venous insufficiency course with placental and systemic oxidative stress

The development of lower extremity venous insufficiency (VI) during pregnancy has been associated with placental damage. VI is associated with increased oxidative stress in venous wall. We have investigated potential disturbance/dysregulation of the production of reactive oxygen species (ROS) in placenta and its eventual systemic effects through the measurement of malondialdehyde (MDA) plasma levels in women with VI. A total of 62 women with VI and 52 healthy controls (HCs) were studied. Levels of nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), 2 (NOX2), inducible nitric oxide synthase (iNOS), endothelial (eNOS), poly(ADP-ribose) polymerase PARP (PARP) and ERK were measured in placental tissue with immunohistochemistry and RT-qPCR. Plasma and placental levels of MDA were determined by colorimetry at the two study times of 32 weeks of gestation and post-partum. Protein and gene expression levels of NOX1, NOX2, iNOS, PARP and ERK were significantly increased in placentas of VI. eNOS activity was low in both study groups, and there were no significant differences in gene or protein expression levels. Women with VI showed a significant elevation of plasma MDA levels at 32 weeks of gestation, and these levels remained elevated at 32 weeks post-partum. The MDA levels were significantly higher in placentas of women with VI. Placental damage that was found in the women with VI was characterized by overexpression of oxidative stress markers NOX1, NOX2, and iNOS, as well as PARP and ERK. Pregnant women with VI showed systemic increases in oxidative stress markers such as plasma MDA levels. The foetuses of women with VI had a significant decrease in their venous pH as compared to those from HC women. The situation of oxidative stress and cellular damage created in the placenta is in coexpression with the production of a pH acidification.     

Microencephaly and microphthalmia in rat fetuses by busulfan

Microencephaly and microphthalmia in the embryos/fetuses from rats exposed to busulfan were histopathologically examined. Busulfan was intraperitoneally administered at 10 mg/kg on gestation days (Days) 12, 13 and 14, and then embryos/fetuses were harvested on Days 14.5, 15, 16 and 21. In the treated group on Day 21, all fetuses were small with reduced body weight, with microencephaly and microphthalmia. On Days 14.5, 15 and 16, apoptotic cells were increased in the neuroepithelium and the neural retina with a width reduction and a decrease in cell density, and the lens epithelial cells histopathologically. Mitotic inhibition was observed in the neuroepithelium, neural retina and equatorial zone of the lens. On Day 21, the cerebral cortex and the retina became markedly thinner. The lens fibers showed swollen, fragmentary and vacuolar formation in the cranial portion accompanied with small lens sizes. The anti-proliferative effects of busulfan brings about a lack of cell populations required for the normal organogenesis of the brain and eye, and leads to microencephaly and microphthalmia, featuring hypoplasia of cerebrum and hypoplasia of retina and lens with cataract, respectively.     

Regulation of sFlt-1 and VEGF secretion by adenosine under hypoxic conditions in rat placental villous explants

The role of adenosine in the regulation of cardiovascular function has long been acknowledged, but only recently has its importance in angiogenesis been appreciated, most notably, through its direct regulation of the proangiogenic growth factor, VEGF. Recent work has established that proangiogenic and antiangiogenic factors, specifically VEGF and and the soluble VEGF receptor fms-like tyrosine kinase-1 (sFlt-1), are directly influenced by hypoxia in placental ischemia. While adenosine has been reported to be an important regulator of VEGF in vascular tissue, the importance of adenosine in regulating VEGF and sFlt-1 in placental tissue is unclear. Here, we have investigated the role of adenosine in the secretion of VEGF and the antiangiogenic protein sFlt-1 in placental villous explants. Under normoxic conditions (6% oxygen), the nonspecific adenosine receptor antagonist, 8-sulphophenyltheophylline (8-SPT) had no effect on either VEGF (P = 0.38) or sFlt-1 (P = 0.56) secretion. However, under hypoxic conditions (1% oxygen), 8-SPT attenuated the increase in the secretion of both VEGF and sFlt-1 (P < 0.05 and P < 0.005, respectively). Exogenous and the adenosine transporter inhibitor dipyridamole (which increases extracellular levels of adenosine) showed differential effects under normoxic conditions: sFlt-1 levels in media increased significantly (P < 0.05), whereas VEGF was unaffected (P = 0.67 and P = 0.19, respectively). These data indicate that extracellular adenosine can regulate VEGF and sFlt-1 secretion in the hypoxic placenta and could, therefore, control the balance of these competing angiogenic factors in diseases characterized by placental ischemia.     

Study of the metanephros of fetuses, newborn and 2-month-old mice developing under conditions of kidney damage to the females by nephrocytotoxic serum]

In the metanephros of foetuses beginning from the 14 days of development and in the newborn mice from females with injured kidneys, marked defects of proximal convoluted tubules and less marked defects of glomeruli were noted what corresponded to the character of kidney injury in their mothers. At the same time the diameter of glomeruli and convoluted tubules, the height and width of their cells increased, but the diameter of their nuclei decreased. These changes are accompanied by distrophic changes, mainly in the cells of convoluted tubules, the most markedly expressed in the newborn mice. No marked histological changes were found in the metanephros of two months old experimental mice.