The influence of exogenous melanin on the development of female Wistar rats' posterity of first generation exposed to low doses at different dose rates during embryogenesis

To research a radio-protective effect of melanin on the reproductive system during its creation the development of first generation posterity (900 descendants) of 125 pubertal female Wistar rats was examined after the single gamma-irradiation with a dose of 1 Gy (mean dose rate of 0.03 mGy/h), which they have been exposed to on the day ten of pregnancy, and the chronic gamma-irradiation with a total dose of 1 Gy (mean dose rate of 5.31 mGy/h) which they have been being exposed to during the first 10 days of pregnancy. The melanin of natural animal origin has the anti-radial effectiveness with the single irradiation increasing the number of alive newborn descendants in a litter and doubling their survival during the first 30 days after the birth. The melanin's effect is less expressed with the chronic irradiation.     

Experimental study of the radioprotective action of melanin on the somatic development during irradiation in the antenatal period of ontogenesis

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats Wistar eliminated the functional deficiency of somatic development revealed at posterity at chronic gamma-irradiation in a doze 1.00-1.25 Gy for all period of pregnancy. The irradiation or introduction melanin antenatal to a phase ontogenesis resulted in stimulation of the immune answer, which was determined at offspring on 3rd week after birth. On the basis of the received data it is concluded presence radioembryoprotective actions melanin in the relation embryotoxic effects of small dozes of ionizing radiation and its participation in regulation immunogenes.     

The influence of the exogenous melanin on the development of the second generation of the female Wistar rats exposed during the critical period of the pegnancy at the nonsterilizing doses of different rate means

The purpose of this study was to estimate the radio-protective activity of melanin for the reproductive status of Wistar rats. Wistar rats were exposed in utero either to the single gamma-irradiation on the tenth day of embryogenesis with the dose of 1 Gy or to the chronic gamma-irradiation with the total dose of 1 Gy during the first 10 days of embryogenesis. Such things like the ability of the rats to conceive, the embryogeny and early postnatal ontogeny of rat's posterity were studied. These doses of the radiation and the melanin did not produce the significant damages of the reproductive function of the survival offsprings of the first generation. The possible mechanisms of radio-protective effect of melanin on reproductive system of animals which have been exposed with the nonsterilizing doses at different mean dose rate were discussed.     

Experimental study of the neuroprotective properties of the melanin in embryos irradiated during antenatal development

Daily introduction per os of the exogenous melanin in a doze of weight of 10 mg/kg pregnant female rats of line Wistar on a background continuous irradiations (dose rate of 2.6 mGy/h within 20 days of pregnancy) eliminated deficiency cognitive functions at posterity. On the basis of the received data it is concluded presence radioembryoprotective actions of melanin in the relation neuro embryotoxic effects of small dozes ionizing radiation. Taking into account small toxicity of melanin, the preparation can be perspective for practical application.     

Embryogenesis and early postnatal ontogenesis of posterity of two generations of female Wistar rats,depending on the time of their fertilization after low dose radiation exposure

On the first day and 3-10 or 40-60 days after a single whole-body gamma-irradiation with doses of 0.25, 0.5 and 1 Gy, the pubertal female Wistar rats coupled with intact males. The embryogenesis and early postnatal ontogenesis of posterity of two generations from these parents were investigated. A raised mutation rate and physiological inferiority of the progeny was found, depending both on a dose and on the degree of oocyte maturity at the moment of the irradiation. The obtained data showed the instability of the irradiated genome in a number of generations.     

Consequences for posterity of two generations of an irradiation pregnant from females rats Wistar in small doses during a bookmark of reproduction system of fetuses development of posterity of the second generation and it reproduction function

With the purpose of study of consequences for development and reproduction functions of posterity of the second generation from females rats Wistar of a total unitary gamma-irradiation in dozes 0.25; 0.5 and 1 Gy (capacity of a doze 0.03 sGy/s) on 10th day of pregnancy (the period of the onset of fetuses reproduction system development) is investigated more than 630 females, 1400 with the age of 19th days, and about 3200 young rats. The revealed deviations(rejections) in development of posterity of two generations parents, antenatal irradiated in not sterilizing dozes, in he period of a beginning of formation of reproduction system, them a variety at different dozes of radiating influence, shown as at posterity of the irradiated mothers, and fathers, testify about instability genoms in a line of generations requiring the account and acceptance of necessary measures for preservation normal genofund.     

The behavioral effects of a single adverse exposure in a number of rat generations: the role of maternal glucocorticoids]

The ionizing irradiation of rat fetuses during the last third of intrauterine development increased blood corticosterone level adulthood and decreased the open field locomotion of their adult offsprings of the next first nonirradiated generation. Treatment of the pregnant rats with glucocorticoids also decreased the offspring locomotion. Irradiation of fetuses in the middle of embryogenesis decreased blood corticosterone level in adulthood and shortened the open-field freezing reaction of their adult offsprings of the next first nonirradiated generation. Adrenalectomy of females before mating decreasing the blood corticosterone level had a similar effect on freezing duration of their adult offsprings. Irradiation of the ancestors within the last third of their intrauterine development had no effect on blood corticosterone level of their adult offsprings of the first generation and produced no behavioral alterations in their descendants of the next second nonirradiated generation. Irradiation of the ancestors in the middle of their embryogenesis decreased the stress-induced corticosterone response in their adult offsprings of the first generation and increased rearings and locomotion in their descendants of the next second nonirradiated generation. The data suggest that a single noxious treatment may have behavioral effects throughout two consequent generations of rats. Mother's glucocorticoid hormones may be one of the factors which transmit the effect.     

Proteolytic processes in lung tissue of rat posterity after whole-body chronic irradiation with low doses

Intensification of proteolytic processes accompanied by inhibited antiprotease activity in lung tissue of first generation posterity of rats irradiated with a total dose of 0.25 Gy (0.01 Gy per day) before gestation was shown. The obtained data satisfied to imbalance in functioning of regulation systems, tension of adaptation mechanisms with possible rapider reduction of adaptation resistance of broncho-lung system of irradiated parents' posterity. Vector changes in correlation of indexes in the proteinase-antiproteinase system were analogous in all experimental series (irradiated male x irradiated female, irradiated male x intact female, intact male x irradiated female) with maximal expression in the group obtained from parents both irradiated before gestation. It could be possible to propose a presence of non-stable genome in posterity of irradiated parents, that satisfied to role of genetic aspects in development of the late functional disorders.     

Supplementation with polyunsaturated fatty acids in pregnant rats with mild diabetes normalizes placental PPARγ and mTOR signaling in female offspring developing gestational diabetes

Maternal diabetes impairs fetoplacental development and programs metabolic diseases in the offspring. We have previously reported that female offspring of pregnant rats with mild diabetes develop gestational diabetes mellitus (GDM) when they become pregnant. Here, we studied the effects of supplementation with polyunsaturated fatty acids (PUFAs) in pregnant mild diabetic rats (F0) by feeding a 6% safflower-oil-enriched diet from day 1 to 14 followed by a 6% chia-oil-enriched diet from day 14 of pregnancy to term. We analyzed maternal metabolic parameters and placental signaling at term in pregnant offspring (F1). The offspring of both PUFAs-treated and untreated mild diabetic rats developed GDM. Although gestational hyperglycemia was not prevented by dietary PUFAs treatment in F0, triglyceridemia and cholesterolemia in F1 mothers were normalized by F0 PUFAs dietary treatment. In the placenta of F1 GDM rats, PPARγ levels were reduced and lipoperoxidation was increased, changes that were prevented by the maternal diets enriched in PUFAs in the F0 generation. Moreover, fetal overgrowth and placental activation of mTOR signaling pathways were reduced in F1 GDM rats whose mothers were treated with PUFAs diets. These results suggest that F0 PUFAs dietary treatment in pregnancies with mild diabetes improves maternal dyslipidemia, fetal overgrowth and placental signaling in female offspring when they become pregnant. We speculate that an increased PUFAs intake in pregnancies complicated by diabetes may prove effective to ameliorate metabolic programming in the offspring, thereby improving the health of future generations.     

Indirect effect of x-irradiation on embryonic development: utilization of high doses of maternal irradiation on the first day of gestation

Two hundred and eighteen female rats were utilized in this study to evaluate the indirect effect of maternal x-irradiation on embryonic development and survival. There were two control groups and ten experimental groups receiving 0, 60, 150, 275, or 400 R on the afternoon of the first day. The use of special shielding devices permitted irradiation of either the mother or the zygote. Several groups of pregnant rats were exposed to 150 R on the afternoon of the first day of gestation. Irradiation of the oviduct and the ova resulted in a 60 to 70% resorption of the implanted ova. Irradiation of the maternal organism while the oviduct was shielded did not increase the resorption rate above control levels. Thus, no indirect effect was demonstrated when the maternal organism received 150 R. When the maternal rats received 400 R and the ova were shielded, 25 % of the implanted embryos resorbed. This was apparently not due to leakage of irradiation around or through the special shielding. Thus, high doses of irradiation in the rat have a moderate indirect effect, but this indirect effect first becomes manifest when the dose of irradiation is above the LD,0 following direct irradiation of the ova. Neither maternal irradiation nor zygote irradiation on the first day of gestation results in an increase in gross congenital malformations or produces fetal growth retardation.     

Mechanisms underlying the programming of small artery dysfunction: review of the model using low protein diet in pregnancy in the rat

Human and animal studies have shown that unbalanced maternal nutrition is associated with the development of cardiovascular and metabolic disease in adulthood. In the Southampton maternal low protein model (SMLP), protein deprivation (50%) throughout pregnancy in rats leads to elevated blood pressure in adult offspring. Impaired peripheral arterial function may contribute to the cardiovascular dysfunction observed in these offspring. This review discusses the impact of such a dietary insult on the vascular function of resistance arteries from pregnant rats (pF(o)), their offspring (F(1)), the pregnant offspring (pF(1)) and the second generation (F(2)). At each stage, disturbances in endothelium-dependent relaxation were observed, implicating changes in endothelial nitric oxide (NO)-guanylate cyclase (GC) signalling pathway in the vascular adaptations to pregnancy and the programmed effects on offspring.     

Peri‐ and postnatal rodent development of Hematide,an erythropoiesis‐stimulating agent

BACKGROUND: Aperi‐ and postnatal reproduction toxicity study was conducted in rats treated with Hematide, a synthetic PEGylated peptidic erythropoiesis stimulating agent (ESA). METHODS: Hematide, at IV doses of 0, 0.5, 3, and 15 mg/kg, was administered from implantation through lactation on gestation days (GDs) 5 and 18 and lactation day (LD) 13. RESULTS: Hematide induced pronounced polycythemia in all Hematide‐treated dams. On LDs 2 and 21, hemoglobin (Hgb) increases above control levels were 3.1, 5.2, and 5.0 g/dL and 4.1, 5.1, and 5.5 g/dL at the 0.5, 3, and 15 mg/kg/dose, respectively. There were no effects on parturition, lactation, or maternal behavior in the F0 generation female rats. A slight decrease in pup viability on postpartum days 2–4 and lower body weights and/or body weight gain for the F1 generation were associated with pronounced polycythemia and decreases in maternal body weight gain and/or food consumption at ≥3 mg/kg/dose. Hematide fetal exposure was negligible. No Hematide effect, other than on growth and survival, was noted on developmental, functional, mating, and fertility end points in the F1 generation rats, and no effect on litter or fetal parameters was observed in the F2 generation. The maternal no‐observed‐adverse‐effect level (NOAEL) for Hematide was 0.5 mg/kg, and the NOAEL for parturition and maternal behavior was 15 mg/kg. The NOAEL for F1 pup viability and growth was 0.5 mg/kg/dose. CONCLUSIONS: In conclusion, the Hematide‐associated adverse findings were attributed to exaggerated erythropoiesis (pronounced and prolonged polycythemia) resulting from administration of an ESA to pregnant animals. Birth Defects Res (Part B) 89:155–163, 2010. © 2010 Wiley‐Liss, Inc.     

Dynamics of reaching imago stage by F1 animals after terahertz irradiation of parental <Emphasis Type="Italic">Drosophila</Emphasis>

Terahertz radiation (0.1–10 THz) is increasingly becoming a factor of human habitat. The study of the consequences of radiation allows one to estimate its possible biological danger. Our data indicate that the terahertz irradiation of parental Drosophila shortens the period of embryonic development of their first generation descendants. Significant deviations of data from the control were found, when both females and males were experimental parents. The highest portion of animals with accelerated hatching as compared with the control was found in progenies from irradiated females. The shift of maximal hatching peak to an earlier period was found in descendants of both sexes. Thus, it was for the first time found on the model object (Drosophila) that the terahertz irradiation of parents can have positive or negative consequences in the first generation descendants.     

Effect of Long-term Fluoride Exposure on Lipid Peroxidation and Histology of Testes in First- and Second-generation Rats

This experiment was designed to investigate the histological and lipid peroxidation effects of chronic fluorosis on testes tissues of first- and second-generation rats. Sixteen virgin female Wistar rats were mated with eight males (2:1) for approximately 12 h to obtain first-generation rats. Pregnant rats were divided into two groups: controls and fluoride-given group, each of which containing five rats. Pregnant rats in the fluoride-given group were exposed to a total dose of 30 mg/l sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/l of NaF throughout the gestation and lactation periods. After the lactation period, the young animals (first generation, F1) were exposed to the same dose of NaF in drinking water for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F1) were killed and testes tissues were taken for histopathological and biochemical analysis. The remaining eight female rats were mated with four males (2:1) for approximately 12 h to obtain second-generation rats. Six female were identified as pregnant and treated with similarly throughout the gestation and the lactation periods. After the lactation period, the young male animals (second generation, F2) were also treated in the same way for 4 months. At the end of the 4 months of experimental period, nine randomly chosen male rats (F2) were killed and testes tissues were collected for histopathological and biochemical analysis. The rats in the control group were applied the same procedure without NaF administration. In biochemical analysis of the fluoride given F1 and F2 rats, it has been found that plasma fluoride levels and testes thiobarbituric acid reactive substance levels were significantly increased when compared with the control group. In F1 and F2 rats, similar histopathological changes were observed. In both groups, spermatogenesis was severely reduced. Spermatogonia and primary spermatocytes were normal, however, there was a widespread degeneration in other spermatogenic cell lines of the seminiferous epithelium. The histological structures of the Sertoli and interstitial Leydig cells were normally observed. It is concluded that chronic fluorosis exposure leads to a remarkable destruction in testes tissues of F1 and F2 rats via lipid peroxidation. The study was carried out in Suleyman Demirel University.     

Effects of semicarbazide on DNA, RNA and protein hepatic levels on four subsequent generations of Wistar rats

1. The offspring (F1) of a parent generation (P) were mated on a brother-to-sister system to produce a second generation (F2), which was then mated in the same way to produce a third generation (F3). 2. Each of these generations were divided into two groups, controls and treated. 3. A single dose of 100 mg/kg of semicarbazide was administered to the treated Wistar rats on the 10th day of their pregnancy. 4. DNA, RNA and protein hepatic levels were measured in the livers of either 21-day-old foetuses or 1, 7, 15 or 30-day-old offspring. 5. These levels were also studied in the pregnant rats on day 21 of gestation. 6. Semicarbazide produced a significant decrease of these levels not only in the foetuses, offspring and pregnant rats but also in the controls, F2 and F3, from treated P and F1 respectively.     

Combined effect of 239Pu and external gamma radiation on pregnant and lactating rats

Exposure of pregnant and lactating rats to external gamma-radiation (12.9-103.2 mC/kg) caused 239Pu redistribution within their bodies. The increase in the transfer of 239Pu to the progeny was maximum after gamma-irradiation of pregnant rats with the dose of 25.8 mC/kg. The decrease in the intake of 239Pu by the progeny was maximum after gamma-irradiation of lactating rats with the dose of 12.9 mC/kg. With the combined effect of gamma- and alpha-radiation gamma-radiation was shown to play the major role in the embryos death.     

Mutagenic effect of cyclophosphan on bone marrow cells of irradiated rats]

The rate of chromosome aberrations in bone marrow cells of male rats was investigated in 24 hours after the cyclophosphan intraperitoneal injection (25 mg/kg). Cyclophosphan was given to rats exposed earlier (15 days, 1, 3, 4, 6 or 9 months before) to X- and gamma-irradiation (400 rads). It was found that preliminary irradiation led to the increase in the mutagenic effect of cyclophosphan as compared to that obtained for intact rats. This effect was demonstrated during 4 months after acute X-irradiation at a dose rate of 70 rads/min and during 1 month after chronic gamma-irradiation at a dose rate of 100 rads/day. Later the effect was shown to disappear in both cases. Chronic irradiation was found to be less efficient in the stimulation of chromosome damages caused by chemical mutagens. The increase of the mutagenic effect of cyclophosphan resulted in the increase of both the number of cells carrying chromosome breaks and the severity of a damage per cell. Different ways of the irradiation effect on the mutagenic action of chemicals are discussed.     

The effects of low doses of low-level gamma-radiation and phenozan injection on structural characteristics of mice spleen DNA

It is well known that AKR mice with spontaneous leucosis are more sensitive to ionizing irradiation as compared to normal F1 (CBA x C57BL) mice. A study on changes of the structural characteristics of spleen DNA and level of protein p53 in the blood serum under the action of low-level gamma-irradiation in a dose of 1.2 cGy and injections of 10(-14) or 10(-4) mol/kg phenozan was performed. The changes in the structural characteristics of DNA (the adsorption on nitrocellulose filters and number of double-strand breaks) and p53 content were observed for each line of mice under gamma-irradiation and each phenozan concentration. Both factors showed long-time post-effects, and structural changes in AKR DNA were consistent with the life span of these mice. Phenozan in the above doses has abolished the induction of double-strand breaks in case of irradiation of F1 mice in a dose of 1.2 cGy and showed long-time post-irradiation effect. These facts suggest a radioprotection property of phenozan.     

Effect of the gaseous hypoxic mixture GHM-10 on the radiosensitivity of the fetus and the development of offspring

A gas hypoxic mixture containing 10 percent of O2 and 90 percent of N2 was shown to exert a radioprotective action on pregnant rats and young rats of the first generation if animals were exposed to ionizing radiation during the periods of preimplantation, organogenesis and fetus development. The effect depended on the radiation dose and the period of the intrauterine development of fetus.     

Synthetic activity of rat blood lymphocytes under acute and continuous gamma-irradiation – fluorescent microspectral study

The effects of different doses of acute and continuous gamma-irradiation on the synthetic activity of rat blood lymphocytes stained with acridine orange were studied by fluorescent microspectrometry. Male rats were exposed to acute gamma-irradiation with doses of 7.5, 4 and 3 Gy, or to continuous irradiation with dose rates of 14.4, 2.1, 1.1 and 0.43 cGy/day, respectively. The changes of the synthetic activity of blood lymphocytes occurred in three main stages after acute gamma-irradiation and in four stages under continuous irradiation. The stages reflect the processes of depression and activation of the immune system under irradiation. Essential differences between the acute and continuous effects were observed in the first stage. After acute gamma-irradiation, the synthetic activity decreased sharply, indicating the predominant contribution of the damaging effect of irradiation, whereas under continuous irradiation, as a result of the stimulatory effect of low-dose irradiation, the synthetic activity increased during the first stage. Received: 11 May 1998 / Accepted in revised form: 10 January 1999