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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.

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.

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.

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.

Ceruloplasmin (CP) expression at the level of formation of its molecular forms in the liver and other rat organs during ontogenesis has been studied. The synthesis of CP commenced on day 15th of embryogenesis and coincided in time with the completion of formation of the fetal liver. This period of rat embryo development was marked by the appearance of two molecular forms of newly formed CP, one of which was secreted in vitro by isolated fetal liver, while the other one was found in the membrane fraction of extrahepatic embryonic tissues. The proportion of CP among the total protein of these fractions increased up to term, correlating with the gain in the embryo weight. The relative content of CP secreted by the livers of newborn animals remained constant up to day 9th of postnatal life and then increased with the age up to approximately 1.5 months. At the same time, the serum concentration of CP remained constant up to day 19th of postnatal life. The increased rate of secreted CP synthesis in the liver during ontogenesis coincided with the appearance of a newly formed non-secreted membrane-bound form of CP in hepatocytes. The ontogenetic dynamics of synthesis of various molecular forms of CP in the liver correlated with the results of immunoblotting of CP polypeptides in Golgi membranes isolated from the livers and the livers and the liver of a 30-day-old rat.

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.

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.

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.

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 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.

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.

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.

Growth and differentiation of neurons and glia in spinal cord explants of 16 days old rat fetuses with teratogen-induced left-sided micromelia were studied. Progressive destruction of astrocytes that differentiate in interstitial zone of cultures was observed in 37% of explants of the left side, while the development was normal in cultures of the right side. Possible mechanisms leading to destruction of astrocytes in cultures of spinal cord regions that innervate anomalous limbs are discussed.

The fecundity of white rats was compared for the night and morning matings (late and early). The mating of animals at the stage of oestrus for 1.5 hrs early in the morning is the optimum one for obtaining females with the precisely dated time of pregnancy. The progeny of females fertilized after 10-11 hours in the morning, i. e. 9-11 hrs after the ovulation, decreases almost twice at the expense of embryonic mortality both prior and after the implantation due to the low viability of "overmatured" eggs.

A combined administration of sodium salicylate and ethanol to female rats in threshold embryotoxic doses on the 9th, 10th, 12th and 13th days of pregnancy results in a sharp increase of embryolethal and teratogenic effects. The embryotoxic effect of sodium salicylate and ethanol at their combined injection exceeds the summational embryotoxic effect at the separate action of the preparations. The spectrum of malformations after their combined effect does not differ from that induced with sodium salicylate.

Reproductive functions and life at laboratory conditions were studied in the lemming. Standard cage-terrariums with a wheel for motion and a plate for drinking are quite convenient. The main ration includes: hay, oats with some carrot added, some apples two--three times a week, sunflower seeds. The animals feel well and reproduce at +8 degrees and +20 degrees in well ventilated rooms. The estrous cycle in lemming females studied by microscopy of vaginal smears is not regular. Only two stages are definitely seen: diestrus and estrus. Intermediate stages--proestrus and metaestrus--can be identified by a successive studies of vaginal smears of the same animal.