[The role of the yolk sac in copper metabolism during rat embryogenesis]. / Rol' zheltochhogo meshka v metabolisme medi v c'mbriogeneze krys.

Using the immunoblotting method, the synthesis of two copper-transporting P1-type ATPases, ATP7A (a candidate for the product of the Menkes disease gene) and ATP7B (presumed product of the Wilson disease gene), in the yolk sac cells of rat embryos at days 11 and 20 of embryogenesis was demonstrated. Concomitantly, yolk sac cells produce ceruloplasmin, a soluble copper-transporting glycoprotein, a proportion of which in secreted proteins progressively diminishes, attaining 5.2% at day 11 and 3.1% at day 20 of development. At different stages of embryogenesis, yolk sac cells synthesize two molecular forms of [14]C-ceruloplasmin, one of which is secreted towards the embryo, whereas the other, towards the decidual membrane. Two forms of ceruloplasmin secreted in polar directions differ in the rate of secretion. The role of the yolk sac as a key organ controlling the delivery and secretion of copper in the embryo during the postimplantation period is discussed.

[The embryo-protective action of antifein derivatives in chloridin-induced teratogenesis]. / Embrioprotektivnoe deistvie proizvodnykh antifeina pri khoridinindutsiruemom teratogeneze.

We studied the effect of propyl- and ethylnorantifein on chloridine-induced abnormalities of extremities in rat embryos. Chloridine (50 and 25 mg/kg, given through the gastric tube) was administered to rats on day 14 of pregnancy, and its embryotoxic effect was estimated from the state of fetuses and implantation sites on day 20 of prenatal development. Propylnorantifein had fetoprotective properties both after intraperitoneal (10 mg/kg) and after intraamniotic (6 and 0.06 micrograms) administration. Ethylnorantifein under similar conditions does not change the action of chloridine, and it prevents the appearance of developmental abnormalities only at the concentration of 0.06 microgram/embryo. These data are discussed in connection with different effects of antifein derivatives on chromatin proteinkinase, which phosphorylates HMG nonhistone proteins.

[A comparative study of the transport dynamics of the peptide moiety of the milk ceruloplasmin molecule in the body of rats with embryonic and adult types of copper metabolism]. / Sravnitel'noe izuchenie dinamiki peremeshcheniia peptidnoi chasti molekuly tseruloplazmina moloka v organizme krys pri émbrional'nom i vzroslom tipakh metabolizma medi.

In chase experiments, we followed the distribution of [125I]-ceruloplasmin prepared from human breast milk orally administered to young rats. Experiments were conducted using six-day-old rat pups (the embryonic type of copper metabolism) or 35-day-old ones (the adult type of copper metabolism). Using the technique of rocket immunoelectrophoresis, we have demonstrated that in six-day-old rats [125I]-ceruloplasmin was transferred from the gastrointestinal tract to the bloodstream and could be detected there over a period of 4 h. In 35-day-old rats, milk ceruloplasmin was digested in the upper part of the intestinal tract. The dynamic aspects of the distribution of labeled milk ceruloplasmin in the body of six-day old rats over a period of 4 h point out that, under the conditions of embryonic copper metabolism, it can serve as a transporter of copper ions to extrahepatic organs. We discuss the role of milk ceruloplasmin in copper metabolism in mammals during the neonatal period.

Population profile of brain asymmetry in rats after intra-amniotic administration of vasopressin.

The effects of intra-amniotic administration of 1-desamino-8-D-arginine-vasopressin (DDAVP) at 14 days of embryogenesis on movement asymmetry in neonatal and mature mongrel white rats were studied. Controls consisted of intact and sham-operated animals, as well as rats given intra-amniotic saline. The population profile of asymmetry was assessed in terms of the tail position of rats aged two days, and also in terms of the direction of excursions in a T-maze in three-months males. The proportion of animals showing asymmetrical tail poses was no more than 36% in controls; the ratio of left-asymmetrical and right-asymmetrical intact rats was 2:1. DDAVP increased the number of rats with asymmetrical tail poses by a factor of 1.5-2.6, and right-asymmetrical individuals became predominant. This effect was demonstrated graphically as a bell-shaped dose-response curve with a peak response at doses of 3 x 10(-8) and 3 x 10(-6) mg. The selection probability for the right-hand side of the maze in experimental animals was 0.71 +/- 0.06, which was significantly higher than in animals of the three control groups, which showed no preference for the direction of excursions. These results indicate lateralization of the action of DDAVP in the developing central nervous system, leading to a predominance of right-sided motor responses in neonatal and mature rats.

[The effect of benzine and formaldehyde on the prenatal development of rats with induced iron trace-element disorder]. / O vliianii benzina i formal'degida na prenatal'noe razvitie krys s indutsirovannym mikroélementozom zheleza.

Iron-deficiency anemia induced in the maternal organism markedly enhances embryotoxic and teratogenic effects of the studied pollutants: gasoline and formaldehyde. The prenatal effects of these drugs against the background of iron-deficiency state in pregnant females leads to development of the main feature of the tissue hypoxia, decompensated metabolic acidosis, in both the maternal organism and 20-day embryos.

[Population profile of brain asymmetry in rats after intra-amniotic administration of vasopressin]. / Populiatsionnyi profil' asimmetrii mozga krys posle vnutriamnioticheskogo vvedeniia vazopressina.

Vasopressin administration induced a right-sided bias in the rat litter, the asymmetry being similar to a right-sided bias in the turning behaviour of adult male rats in the T-maze. The findings suggest the nigrostriatal system to be responsible for the lateralising effect of vasopressin in the brain.

Embryotoxicity of silver ions is diminished by ceruloplasmin--further evidence for its role in the transport of copper.

The effect of alimentary administration of silver salts upon embryogenesis in rats was studied. Feeding of female rats throughout the term on a regular diet supplemented with AgCl did not cause alterations of their physiological functions, despite the fact that enzymatically active copper-containing ceruloplasmin (CP) was eliminated from the blood plasma. However, developmental abnormalities of embryos, their prenatal death or the 100% mortality of the newborns in the first 24 h of life was seen. Copper content in placenta and fetal tissues was strongly diminished. Cu, Zn-superoxide dismutase (SOD) activity decreased in cytoplasm of embryonic cells along with a drop, though less pronounced, in the tissues of the pregnant females. Embryotoxicity of AgCl was seriously diminished by repetitive injections of native CP to the pregnant rats. Such treatment resulted in an increase of SOD activity in placenta and embryonic tissues. The mortality of the newborns also became less. It is suggested that the embryotoxic effect of AgCl is caused by its ability to interfere with copper metabolism, in particular by altering the copper-transporting function of CP.

[The toxic effect of serotonin in direct and mediated actions on rat embryos]. / Toksicheskii éffekt serotonin pri priamom i oposredovannom deistvii na émbriony krysy.

Embryotoxic effect of serotonin in direct (intra-amniotic administration) and indirect (subcutaneous administration) treatment was studied. In both cases serotonin causes embryo death and different abnormalities in development in small number of embryos. Mechanism of serotonin embryotoxic effect is under discussion.

[The role of the maternal genotype in the realization of the embryotoxic activity of teratogens]. / Rol' genotipa materi v realizatsii émbriotoksicheskoi aktivnosti nekotorykh teratogenov.

Against the background of the induced iron deficit ethanol (6.4 g/kg) causes aggravation of the embryolethal effect and anomalies in 15% of embryos in 14-day pregnant rats. Changes in the genome of rat males and females after the injection of the plasmid with a foreign gene at the stage of two pronuclei and the subsequent crossing with intact animals account for the increase in sensitivity of embryos to subteratogenic doses of sodium salicilate. The maternal organism disturbances have a more pronounced effect than the paternal ones.

[Influence of ceruloplasmin on the embryotoxic effect of silver ions]. / Vliianie tseruloplazmina na émbriotoksicheskii éffekt ionov serebra.

The effect of alimentary administration of silver salts upon embryogenesis in rats has been studied. Feeding of AgCl to pregnant female rats throughout gestation did not result in any alterations in their physiological functions, although the active copper-containing ceruloplasmin (Cp) was eliminated from the blood stream. However, anomalous development of embryos, their prenatal death or total mortality of newborn rats within the first 24 hours after birth were evidenced. The copper content in the placenta and embryonic tissues decreased appreciably. The Cu,Zn-superoxide dismutase (SOD) activity was diminished in the cytoplasm of embryonic cells alongside with its drop, though less pronounced, in the tissues of the pregnant females. The embryotoxicity of AgCl was considerably reduced by repetitive injections of native Cp to pregnant rats. Such treatment caused an increase in the SOD activity in the placenta and embryonic tissues. Mortality of the newborns also went down. It is suggested that the embryotoxic effect of AgCl is due to its ability to interfere with copper metabolism, by altering the copper-transporting function of Cp.

[A comparison of the characteristics of chromosome nondisjunction in the first maturation division of mouse oocytes heterozygous for balanced structural rearrangements of the chromosomes]. / Sopostavlenie osobennostei neraskhozhdeniia khromosom v pervom delenii sozrevaniia ootsitov myshei, geterozigotnykh po sbalansirovannym strukturnym perestroikam khromosom.

Peculiarities of non-disjunction of chromosomes in the first meiosis of maturation of oocytes in mice heterozygous in the Robertsonian and nonuniform reciprocal translocations have been determined. Mice, heterozygous in one Robertson's translocation, had general frequency of chromosomal non-disjunction in the 1st meiosis of oocyte maturation equal to 17%; by two Robertsonian translocations the total frequency of genetically deficient oocytes amounted to about 77%, in case of unequal reciprocal translocation--to 50%. In two latter cases genetic disturbances were due to unbalanced euploid chromosome sets.

[Biosynthesis and secretion of ceruloplasmin by rat mammary cells during lactation]. / Biosintez i sekretsiia tseruloplazmina kletkami molochnoi zhelezy v period laktatsii u krys.

Some peculiarities of rat milk ceruloplasmin (CP) biosynthesis have been analysed. Electrophoretic and immunoelectrophoretic data suggest that rat milk contains up to 20 mg/100 ml of CP. Rat milk CP is represented by a single molecular form whose molecular mass, enzymatic activity and antigenic properties are fully identical with those of serumal CP. According to the dot hybridization date, the CP-mRNA content in rat mammary cells is about ten times as low as that in adult rat liver. Analysis of polyribosomal RNA by blot hybridization of RNA-cDNA revealed that rat mammary CP-mRNA is represented by a single molecular form, 3.5 kb in length, whose molecular mass is identical with that of the predominant CP-mRNA of rat liver. The dynamics of secretion of the de novo synthesized CP into rat milk indicates that the CP synthesis and secretion occur independently of the serumal CP. In vitro and in vivo pulse labelling studies demonstrated that rat milk CP is synthesized and secreted by rat mammary cells.

[The embryotoxic effect in rats exposed to the blood serum of newborn infants tested for the presence of transfer factors]. / Embriotoksicheskii éffekt u krys pri vozdeistvii syvorotkoi krovi novorozhdennykh detei, testiruemykh na nalichie transfernykh faktorov.

Pregnant rats (day 14 of gestation) received intraamniotic injections of newborn human serum. Transfer factors (TF) present in injected serum produced significant embryotoxic and teratogenic effects, as well as changes in coordination of motor activity (EMG) in newborn rats. The extent of embryological disturbances and the motor activity of 33- to 34-day old recipient rats depend on TF concentration (at serum dilution 1:2) and on the state of infant's motor functions ("normal" group and "risk" group). The results obtained allow to objectively determine the pathogenic effect of serum TF on embryotoxicity and formation of motor coordination in the donor infant.

[The mechanisms of the teratogenic action of alcohol]. / Mekhanizmy teratogennogo deistviia alkogolia.

Under study was the influence of different doses and methods of administration of ethanol on embryogenesis of rats and the effect of some shifts in homeostasis of a female rat on a manifestation of teratogenic effect of ethanol. Embryogenesis of rats is resistant to action of ethanol and acetaldehyde. Shift in the acid-base balance to the acid side is not thought to be determining in the mechanism of the appearance of the fetal alcohol syndrome, while the embryotoxic effect of ethanol manifests itself against the background of an iron-deficient state of the maternal organism.

[The stage-specific sensitivity of rat embryogenesis to ethanol administered intra-amniotically and by other methods]. / Stadiospetsificheskaia chuvstvitel'nost' émbriogeneza krys k étanolu pri vnutriamnioticheskom i drugikh sposobakh vvedeniia.

The exposure of rat fetuses to ethanol by direct intra-amniotic injection in the afternoon of the 14th day of embryogenesis resulted in developmental anomalies (34%), the defects located mostly in the left extremities. Intraperitoneal injections of ethanol at the same period of pregnancy resulted in analogous injuries but only in occasional fetuses. There was no embryotoxic effect after exposure to high doses of ethanol by per os. It was concluded that even a single dose of ethanol in certain periods of pregnancy and in certain homeostasis disorders in the maternal organism could induce the fetal alcohol syndrome (FAS) in the newborns.

[The prevention of congenital developmental anomalies in rats]. / Profilaktika vrozhdennykh anomalii razvitiia u krys.

Preventive administration of Eleutherococcus XXX extract during prenatal and pre-embryonic periods of development prevents embryotoxic effect of subsequent treatment of pregnant rats with ethanol and sodium salicylate. Eleutherococcus abolishes embryotoxic and teratogenic effects of ethanol manifested against the background of experimental syndrome of iron deficit in pregnant females. Mechanism of its antiteratogenic action is probably based on stimulation of cell detoxification mechanisms, increase in energy potential of cells, as well as on stabilization of structural and functional state of cell membranes.

[The effect of amniotic fluid taken from women in labor on the morphofunctional development of fetal and newborn rats]. / Vliianie amnioticheskoi zhidkosti, vziatoi u zhenshchin vo vremia rodov, na morfofunktsional'noe razvitie plodov i novorozhdennykh krys.

Amniotic fluid from women was injected intra-amniotically to rats at the 14th day of pregnancy in a dose 0.3 ml. Morphological and functional parameters of embryonic development of rats and EMG activity of rat puppies at the age of 30-34 days differed from control ones with respect to the degree of maturity and motor disturbances of newborn babies. The data obtained reveal not only evident but also masked forms of motor pathology which was observed in children later, namely to 6-9 months. Chronic motor pathology in rat puppies was unilateral with central motor disturbances in babies being directly related to the degree of these disturbances.