[ANALYSIS OF THE POSSIBLE RELATION OF FETAL DAMAGE AND DRUGS. V. PRELIMINARY STUDY ON THE INFLUENCE OF 4 ANTIEMETICS ON FETAL DEVELOPMENT].
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Two studies were conducted to evaluate the interactive effects of alcohol and lead during pregnancy in rats. Our purpose was to see if lead, as lead acetate, would influence the alcohol effect already known to exist. In the first study, pregnant Long-Evans rats received lead (as lead acetate), alcohol (20% w/v), or lead plus alcohol once a day on gestation days (GD) 10-20. On GD 20, when animals were sacrificed, mean blood alcohol levels were consistently higher for the lead-plus-alcohol-dosed groups compared to alcohol alone, but these two groups did not differ in maternal weight gain, percent resorptions, litter size, or fetal weight. Mean blood lead levels were not consistently higher in the lead-plus-alcohol groups compared to lead only, but the lead-plus-alcohol groups differed significantly from the lead-only groups at higher doses in the previously mentioned parameters. The lead-only groups did not differ from vehicle controls in any parameter in spite of blood lead levels as high as 300 micrograms/dl. In the second experiment, animals given a combination of alcohol and lead did not differ in activity, passive avoidance, or active avoidance learning compared to animals given alcohol or lead alone. Animals given lead only or the combination of lead plus alcohol had longer first trial latencies in the passive avoidance test. The data indicate that neither lead nor alcohol attenuates or potentiates each other's effects on reproduction or learning behavior in the Long-Evans rat even at high blood lead levels.
We investigated the influence of restricted maternal nutrition between 28 and 77 d of gestation on placental weight and appearance, and on fetal weight and conformation. Single-bearing ewes were fed either twice [i.e. controls (n = 19)] or half [i.e. nutrient-restricted (n = 28)] their energy requirements from 28 to 77 d of gestation, after which all ewes were fed to fully meet the energy requirements for maintenance and pregnancy. Close to term (145 +/- 1 d) placental weight was higher in the nutrient-restricted group [nutrient-restricted, 416.3 +/- 12.6 g; controls, 347.4 +/- 17.6 g (p < 0.01)], as was the abundance of everted placentomes. There was no significant difference in total fetal weight, or weights of individual organs between groups, but crown-rump length was significantly greater in lambs born to nutrient-restricted ewes [nutrient-restricted, 50.4 +/- 0.4 cm; controls, 48.2 +/- 0.6, cm (p < 0.01)]. Fetal to placental weight ratio was lower in the nutrient-restricted group [nutrient-restricted, 9.51 +/- 0.23; controls, 10.81 +/- 0.39 (p < 0.01)]. A stronger relationship between the total weight of the fetal component of the placental and fetal weight was observed in controls (r2 = 0.50) than in nutrient-restricted ewes (r2 = 0.18). In conclusion, maternal nutrient restriction over the period of rapid placental growth results in a larger placenta and altered placental to fetal weight ratio if ewes are subsequently fed to requirements for the remainder of gestation.
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OBJECTIVE: Detection of the corpus callosum in the developing fetus on sonograms usually is difficult. We determined the normal appearance and development of this structure during the second half of pregnancy, as shown on transvaginal sonograms. SUBJECTS AND METHODS: One hundred one fetuses were evaluated with transvaginal sonography between 18 and 42 weeks' gestation. The length of the corpus callosum and the thicknesses of the genu, body, and splenium were measured, and growth tables were produced. RESULTS: The corpus callosum was detected in 95% of cases and showed gradual enlargement during pregnancy; growth was linear, from nearly 17 mm in length at 18 weeks' gestation to 44 mm at term. The ratios of the length of the corpus callosum to the anteroposterior diameter of the brain remained relatively constant from 20 to 21 weeks' gestation to term. CONCLUSION: Transvaginal sonography can be used to visualize and measure the corpus callosum in the developing fetus. Data from this study may be useful as a reference for normal development of the corpus callosum.
The paper determines the mechanism of a noxious effect of lead upon the organism of a child. The authors identify the environmental sources of lead and discuss its metabolism in human body. They also determine the mechanism of toxic lead effect with a special emphasis placed on its transport through the placenta and the resulting detrimental effects for the fetus. The paper also discusses the results of prospective studies indicating a correlation between the exposure of a pregnant woman to lead and the future mental development of her child.
L-leucine, an essential amino acid, is one of the most popular ingredients in dietary supplements. To investigate a possibility of its embryo-fetal toxicity in rats, 11- to 12-week old dams were orally administered an aqueous solution of L-leucine at doses of 300 or 1000 mg/kg body weight on gestational days 7-17. Body weight and feed intake was evaluated throughout the whole course of pregnancy (days 0-20). L-Leucine did not influence body weight, but at a dose of 1000 mg/kg, slightly enhanced feed intake on days 14 and 18 of pregnancy. Caesarean section (day 20) revealed no influences on the litter size and weight of live-born fetuses, the number of corpora lutea, implantation index or the quality of placenta, and the minor increase in feed intake was considered irrelevant to the pregnancy outcomes. Fetuses were evaluated in a battery of external, visceral and skeletal examinations. No effects of L-leucine on gender ratio and external abnormalities, and no significant treatment-related variations in visceral and skeletal pathologies were observed. These results suggested that L-leucine, administered orally during organogenesis at doses up to 1000 mg/kg body weight, did not affect the outcome of pregnancy and did not cause fetotoxicity in rats.
The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA binding capability of Jun-Jun homodimers and Fos-Jun heterodimers by altering their redox state and to be involved in calcium mediated transcriptional repression of the parathyroid hormone gene. Previous studies examining the tissue specific distribution of the AP endonuclease (APE) transcript and protein by Northern analysis and enzymatic assays, respectively, have shown that this gene is expressed in all tissues at relatively similar levels. In the current study, adult and fetal rat tissue sections were examined for the expression of the APE transcript in specific subpopulations of cells and during development by in situ hybridization. In the adult brain, the APE transcript showed a widespread, but heterogeneous pattern of expression. Predominant levels of transcript were detected in the suprachiasmatic nuclei, the supraoptic and paraventricular nuclei, the hippocampus and the cerebellum. During fetal development, transcript was detected in all somatic sites examined with very high levels in the thymus, liver and developing brain. Examination of the adult testis indicated that the expression of the transcript varies with the stage of spermatogenesis with the highest levels being present over round spermatids. These results provide evidence that the APE gene is not homogeneously expressed, but rather is found in subpopulations of cells in the brain and testes and during development.
Mouse esophageal muscle is composed of skeletal muscle in the adult, but it has been proposed to be derived from differentiated smooth muscle cells by transdifferentiation during late fetal and early postnatal development (Patapoutian et al. [1995] Science 270:1818-1821). We characterize skeletal muscle precursors in mouse esophagus by investigating the expression of four myogenic regulatory factor transcripts: MyoD, Myf-5, myogenin, and MRF4. Myf-5 was first detected at cranial region of esophageal muscle at 12-13 days of gestation, followed by coexpression of MyoD and MRF4 at 14 days of gestation, and myogenin at embryonic day 15. The expression of these myogenic factors showed outer to inner layer and cranial to caudal progression during fetal and early postnatal development of mouse esophagus. The early appearance of myogenic regulatory factors starting at 12-13 days of gestation indicates that the cells in the mouse esophageal wall are committed to become skeletal muscle-type cells before any differentiated smooth or skeletal muscle cells are observed at 14-15 days of gestation.
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