Developmental effects and mineral interactions in rats fed textured vegetable protein

The teratogenic effects of feeding a diet based on textured vegetable protein to Long-Evans rats were studied along with maternal and fetal mineral interactions and their relationship to diet composition. Pregnant rats were fed purified diets containing 18% protein as casein (CAS), textured vegetable protein (TVP, from defatted soy flour) with 18 mg Zn/kg, or TVP diet with 100 mg Zn/kg. A fourth group was fed diet NIH-31. The animals received their diets throughout pregnancy and were sacrificed on day 20 of gestation. Fetuses were examined for developmental effects, and mineral levels were determined in maternal and fetal tissues by inductively coupled argon plasma-atomic emission spectrometry. Females fed the casein diet or diet NIH-31 had normal weight gains throughout pregnancy and their progeny exhibited normal development. The animals on the TVP-containing diet with 18 mg Zn/kg had decreased food consumption and body weights, and their fetuses exhibited developmental anomalies as well as reductions in size and weight. These developmental alterations may be the result of decreased zinc levels in the fetal tissues, caused by reduced bioavailability of the trace element in the maternal diet. Significant increases in tissue iron accompanied the low zinc levels. No developmental effects were found in animals receiving the high Zn-TVP diet, and mineral data from these animals were not significantly different from the casein group.     

Influence of dexamethasone on growth and development of rat fetuses: changes in nucleic acids and protein content

Pregnant rats were treated with dexamethasone in drinking water (10 micrograms/ml) from the 15th to the 22nd day of pregnancy. Dexamethasone significantly reduced the weight of rat fetuses and concentration of DNA, RNA and proteins in fetal adrenal glands, liver, placenta, brain, kidneys, heart, lung, testes and pituitary from the 17th to the 22nd day of pregnancy. These data show that dexamethasone given to pregnant rat may lead to potentially deleterious effects on fetal rat development.     

Influence of doxycycline administration on rat embryonic development during organogenesis

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty‐one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day‐fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.     

Caffeine and reduction of fetal ossification in the rat: fact or artifact?

This study was done to determine the gestational period during which the rat fetus is susceptible to reduction of skeletal ossification by caffeine. Caffeine, 100 mg/kg/day by gavage, caused the greatest reduction in ossification, as assessed by staining with alizarin red S, in fetuses exposed between day 16 to 19 of gestation, less in those treated between day 7 to 19, and markedly less in those receiving it between day 7 to 16; a single dose on day 19 had very little effect. This indicates that the fetus is most susceptible late in pregnancy. Bones in early stages of mineralization on day 20 showed a greater reduction in staining than those in later stages. Thus, caffeine appears to lower the rate of ossification rather than reduce its final extent. In the day 7 to 19 caffeine treatment group, but not in the day 16 to 19 group, maternal and fetal body weights were reduced, and 1.6% of the fetuses had aphalangia. The day 7 to 16 caffeine treatment reduced fetal body weight. This argues against an association between reduction in fetal weight and ossification. None of the treatments affected rates of resorption or litter size. A novel and important observation made is that the different caffeine treatments affected the staining by alizarin of both claws and bones in a qualitatively and quantitatively similar manner. Since claws are devoid of osteoid, this observation questions the specificity of alizarin for the assessment of the state of fetal ossification and raises doubt as to the significance of the observed action of caffeine on ossification.     

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.     

Reduced weight in mice offspring after in utero exposure to 2450-MHz (CW) microwaves

Time-bred CD-1 mice (100) were sham-irradiated or irradiated with 2450-MHz (CW) microwaves at 28 mW/cm² for 100 minutes daily from the 6th through 17th day of gestation. The offspring were examined either as fetuses after hysterotomy on the 18th day of gestation or as naturally born neonates on the 1st and 7th day of age. Fetuses of half of the dams were examined on the 18th day of gestation. The incidence of pregnancy and the numbers of live, dead, resorbed, and total fetuses were similar in both groups. The mean weight was significantly lower (10%) in live microwave-irradiated fetuses, and ossification of sternal centers was significantly delayed. In the offspring that were born naturally, the mean weight of microwave-irradiated 7-day-old suckling mice was significantly lower (10%) than that of the sham-irradiated group. Survival rates of neonates in these two groups were not different. These data demonstrate that the decreased fetal weight seen in microwave-irradiated mice is retained at least 7 days after birth. Evidence from other published studies is presented to show that the retarded growth is persistent and might be interpreted as permanent stunting.     

Influence of ACTH secreting tumor (MtTF4) on fetal rat adrenal gland steroidogenesis in vitro in prolonged pregnancy

Pregnant female rats with ACTH secreting tumor (MtTF4) have prolonged pregnancy and cannot deliver. The fetuses of tumor bearing females have in prolonged pregnancy on days 24 and 25 of pregnancy greater body weight and smaller adrenal weight as compared to intact fetuses of the 22nd day of pregnancy. The fetal adrenal glands converted to vitro 4-14C progesterone to radioactive 11-deoxycorticosterone (DOC), corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B) and aldosterone. Fetal adrenal glands in prolonged pregnancy synthetized in vitro less amount of radioactive DOC, B and 18-OH-DOC. A negative relationship exists between the maternal corticosterone which passes the placenta to fetuses and corticosteroidogenesis of fetal adrenal glands. These results indicate the possibility that fetal rat adrenal glands with their corticosteroids participate in pregnancy and influence normal delivery.     

Lead exposure on critical days of fetal life affects fertility in the female mouse

Female mice were exposed to lead in utero by intravenous injection of lead chloride into the mothers at different stages of pregnancy. At a mature age the mice exposed as fetuses (F1 generation) conceived at a normal rate, but the litter size and fetal survival varied significantly. Small litters and increased numbers of fetal deaths were observed in mice exposed to lead on day 8 of intrauterine life. The live fetuses in this group were normal with respect to weight and morphological appearance. Serum levels of estradiol and progesterone, measured on day 17 of pregnancy, did not differ significantly between F1 mice of a control, unexposed group and of the group exposed to lead on day 8 of intrauterine life. Ovarian follicle counts revealed a significantly smaller number of primordial follicles in the latter group. It is suggested that the exposure to lead at a time of early organogenesis caused the observed fertility decrease by interfering with the development of the female germ cells.     

The effect of ethylmercury on fetal development and some essential metals levels in fetuses and pregnant female rats

Ethylmercuric chloride (EtHg), at the dose of 2.5 mg Hg/kg, was administered by gavage every other day to pregnant rats from d 6 to 20 of gestation. On the 21st day of gestation, females were sacrificed to allow the evaluation of embryotoxicity and take the material for analytical determinations. Copper, zinc, iron, and calcium were determined by AAS in liver, kidneys, brain, intestines of fetal and pregnant female rats, as well as in maternal spleen, whole blood, placenta, and fetal carcass. Ethylmercury caused a decrease of the body weight gain during gestation and diminution of relative liver weight of intoxicated females. This compound also induced fetotoxic effects, evidenced by slight diminution of the length as well as the weight of fetuses. It was found that the effect of EtHg on the levels of endogenous metals is different in females and fetuses. In pregnant females, EtHg administration resulted in a significant increase of copper levels in kidneys, liver, and spleen: and in the decrease of zinc concentration in the kidneys, but an increase in placenta and blood compared with pregnant controls. EtHg induced slight decrease of iron concentration in kidneys and intestinal wall of pregnant females. The concentrations of iron in liver and kidney and of zinc in whole blood and liver were lower in control pregnant rats than those in control non-pregnant females. In fetuses of EtHg-exposed mothers, increases in kidney zinc and liver calcium levels were found, whereas tissue copper and iron concentrations were the same as in controls.     

蝉棒束孢子实体的致畸性评价及对高血糖小鼠血糖的影响

对妊娠第7-16天Wistar大鼠连续给予口服蝉棒束孢子实体低、中、高3个剂量（0.85、1.70、3.40g/kg）10d,观察给药组对大鼠孕期体重、死胎率、吸收胎率、活胎数、每窝平均胎仔数、胎鼠重、胎鼠身长、前囟宽度、子宫连胎重及胎鼠外观、内脏发育、骨骼发育的影响,研究妊娠动物接触蝉棒束孢子实体后引起的致畸可能性。对正常小鼠、STZ致高血糖模型小鼠给予口服不同剂量的人工培植蝉棒束孢子实体（0.4、0.25、0.125g/kg）,测定空腹血糖及糖耐量,评价蝉棒束孢子实体的降血糖作用。结果表明：与阴性对照组相比,人工培植蝉棒束孢子实体各剂量组在大鼠孕期体重、死胎率、吸收胎率、胎鼠重、胎鼠身长和前囟宽度、胎鼠外观、内脏和骨骼发育等方面均无显著性差异（P>0.05）;与模型对照组（0g/kg BW）相比,人工培植蝉棒束孢子实体中、低两个剂量组均能降低STZ致高血糖模型小鼠给葡萄糖后0.5h血糖水平（P<0.05）,低剂量组能明显降低高血糖模型小鼠0-2h血糖曲线下面积,且对小鼠体重及正常小鼠空腹血糖均无不良影响。提示人工培植蝉棒束孢子实体对大鼠无明显的母体毒性、胚胎毒性和致畸性;对高血糖小鼠具有降血糖的作用。     

Nucleic acid content and growth of fetal brain, liver and heart during inanition in pigs

Previous investigations have indicated that gilts deprived of dietary intake for periods up to 40 days are capable of maintaining pregnancy and producing offspring of normal body weight. The present experiment was designed to study the effects of inanition during middle or late pregnancy on growth and on protein and nucleic acid content of porcine fetal brain, liver and heart. Gilts were subjected to prolonged inanition (40 days; 0 kcal/day; water only) during either the middle third (Days 30-70, n = 3) or last third (Days 70-110, n = 3) of pregnancy; controls received a full diet (7028 kcal/day) until Day 70 (n = 3) or 110 (n = 3) when all dams were hysterectomized. Inanition during middle or late pregnancy had no detrimental effect on fetal brain development. Brain weight, cell size (protein/DNA ratio) and cell number (total DNA) were similar in all fetuses at Day 70 or 110. RNA concentrations at Days 70 and 110, protein concentration at Day 70 and total protein at Day 110 were higher in fetuses from starved dams than in those from controls, indicating greater protein synthetic activity in fetal brains from nutrient-deprived dams. Prolonged inanition during midpregnancy had only a limited effect on fetal liver and heart. Only liver RNA concentration and content at Day 70 differed in fetuses from starved dams; however, 40 days inanition during late gestation had marked detrimental effects. Liver weight, cell size and cell number were reduced in inanition as compared with controls by Day 110.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in the fetal tibial growth plate secondary to maternal zinc deficiency in the rat: a histological and histochemical study

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. To elucidate further the effects of maternal ZD in the fetal skeleton, we performed a morphological and histochemical study of tibial growth plate (GP) in ZD rat fetuses. The histochemical study included the identification of calcium, of hydrolytic enzymes associated with the process of calcification, and of oxidative enzymes related to energy production and to the synthesis of proteoglycans. Pregnant Sprague-Dawley rats were fed (1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), (2) a zinc-deficient diet (0 micrograms/g) ad libitum (group ZD), or (3) the control diet pair-fed to the ZD rats (group PF). On day 21 of gestation, laparotomies were performed, the fetuses were removed, and fetal tibiae obtained. Specimens were stained with hematoxylin-eosin (H&E) and Masson Trichrome and were processed for identification of alkaline phosphatase, adenosine triphosphatase, succinic dehydrogenase, NADH dehydrogenase, and calcium. The morphologic patterns found in ZD fetal tibiae indicated defects in various cell types implicated in bone metabolism. Staining for hydrolytic enzymes revealed alterations in the size and distribution of matrix vesicles and a weaker staining for ATPase in ZD fetuses. Staining for oxidative enzymes was overall more intense in ZD fetal tibiae. ZD fetuses also presented irregular and defective calcification. These findings indicate that severe maternal ZD in the rat results in structural and functional alterations in the GP of fetal bone, leading to a defective endochondral ossification.     

Evaluation of heart malformations in B6C3F1 mouse fetuses induced by in utero exposure to methyl chloride

C57BL/6 female mice impregnated by C3H males mice to produce B6C3F1 fetuses were exposed daily for six hr to atmospheres containing 0, 250, 500, or 750 ppm methyl chloride, from gestation day 6 to gestation day 18. There were 74 to 77 females with copulation plugs per exposure concentration. Females exposed to 750 ppm ethyl chloride exhibited ataxia commencing on the seventh day of exposure (gestation day 12). They also showed hypersensitivity to touch or sound, tremors and convulsions. Six females in the 750 ppm group died and one was euthanized in extremis prior to scheduled sacrifice. On gestation day 18, all other females were euthanized for evaluation. Only dams exposed to 750 ppm exhibited significant decrease in body weight by gestation day 18, weight gain during the gestation period, and absolute weight gain (weight gain minus gravid uterine weight) versus controls. There were no treatment related-effects on these parameters in the other exposure groups. None of the groups exhibited exposure-related differences in pregnancy rate, gravid uterine weight, or maternal liver weight. There were no differences in the numbers of implantations, resorption, dead fetuses, nonlive (dead plus resorbed) fetuses, live fetuses, sex-ratio, or mean fetal body weight per litter. There was a significant exposure-related increase in the number and percentage of affected (nonlive plus malformed) fetuses per litter with the incidence of affected fetuses in the 750 ppm group significantly higher than controls. There was a statistically significant increase in the incidence of heart defects in the 500 and 750 ppm group relative to controls. Of the 37 fetuses in the study with heart defects, 23 were females, 14 were males. The heart defects observed included: absent or abnormal tricuspid valve, reduced number of papillary muscles and/or chordae tendineae on the right side, small right ventricle, globular heart, and white spots in the left ventricular wall. Multiple malformations were observed in one fetus from the 500 ppm group and in three fetuses in the 750 ppm group. It is concluded that methyl chloride inhalation exposure to pregnant C57BL/6 mice from gestation day 6 through gestation day 17 resulted in maternal toxicity only at the 750 ppm exposure concentration and was teratogenic to B6C3F1 conceptuses at exposure concentrations of 750 and 500 ppm, leading to fetal heart malformations. No evidence of embryo or fetotoxicity other than teratogenicity was seen at any of the exposure concentrations employed. No maternal, embryo or fetotoxicity or teratogenicity was associated with exposure of mice, during critical periods of embryo and fetal development, to 250 ppm of methyl chloride.     

Studies on the growth of the fetal guinea pig. The effects of ligation of the uterine artery on organ growth and development

The effects of reduced maternal placental blood flow on the growth and development of the fetal guinea pig have been studied by unilateral ligation of the uterine artery at day 30 of pregnancy. Fetal guinea pigs were investigated about 20 or 30 days later. In about one-third of cases fetal death occurred, in another third fetuses less than 60% of normal weight were observed and in the remainder all fetuses were in the normal weight range. In the growth retarded fetuses prenatal growth occurred at about 50% of the rate in control. There was no postnatal 'catch up' as growth still remained lower than in controls. Restricted fetal growth affected particularly development of the visceral tissues in which case size declined in proportion to body weight. Brain and adrenal by comparison were less affected as their contribution to total body weight increased, but even so in the severely retarded fetuses the mass of both fell. The responses of the liver were in general consistent with a delay in the pattern of development. Thus DNA, RNA, protein and haematopoietic cell content changes occurred later than normal. In contrast an enhanced deposition of glycogen was apparent in the liver of the growth-retarded fetus. The results indicate some of the ways in which nutritional deprivation of the fetuses leads to reprogramming of growth and maturation of selected fetal tissues to allow non-essential changes to await more favourable times.     

Effects of AET and MEA treatment of mice on the first day of pregnancy

Porton female mice were injected intraperitoneally with 2-aminoethylisothiouronium bromide hydrobromide (AET) or cysteamine hydrochloride (MEA) in a dose of 40 mg/kg of body weight on the first day of pregnancy. On the last, nineteenth, day of gestation, taking into consideration females in whose uterus live fetuses were observed, the increase in their body weight throughout pregnancy, the number of fetuses in the uterus, the body weight of fetuses, and placental weight were found smaller in mice treated with AET or MEA, than in control ones. Among the injected compounds, AET appeared to be less toxic than MEA.     

Hypervitaminosis A resulting in DNA aberration in fetal transgenic mice (Muta Mouse)

Treatment with excessive amounts of Vitamin A during maternity induces fetal malformations. However, it is unclear whether these malformations are due to gene mutations or not. Using transgenic mice (containing lacZ gene showing beta-galactosidase enzymatic activity), we planned to observe whether gene mutations occur in the fetal tissues after treatment during maternity with Vitamin A (retinol palmitate). On the 11th day of pregnancy, mothers were given 30 mg (group 2), 150 mg (group 3) and 300 mg (group 4) of Vitamin A/kg body weight orally. Fetuses obtained on the 18th day of gestation showed malformations, such as cleft palate, origodactyly, brachydactyly and ectromeria. Most notably, cleft palate occurred dose dependently. The incidental rates were 100% in group 4, 58% in group 3 and 6% in group 2. The number of dead and absorbed fetuses also increased dose dependently with the treatments. DNA (integrated vectors containing lacZ genes) extracted from each fetus showed Vitamin A-induced lacZ mutations, especially in the malformed fetuses. The mutation frequencies were 4.99x10(-5) in group 4, 5.28x10(-5) in group 3 and 4.26x10(-5) in group 2. The frequencies of group 3 were significantly higher (p<0.05) than that of the controls (group 1), 2.79x10(-5). Maternal treatment with Vitamin A (150 mg/kg of body weight) was carried out on the 11th day of pregnancy. Fetuses obtained on the 14th day of gestation showed a much higher incidence of mutation, approximately 8.91x10(-5) (group 6) that was significantly higher (p<0.0001) than those from the controls (group 5), 2.94x10(-5). The present study indicates a possibility that hypervitaminosis A-induced fetal malformation and death might be caused by gene mutations.     

Effects of low-frequency magnetic fields on fetal development in rats

We studied effects of alternating magnetic fields on the embryonic and fetal development of rats. Mated females of the Han:Wistar-strain were sham exposed or exposed continuously to a 50-Hz field or to a 20,000 pulse-per-second (pps) sawtooth magnetic field from day 0 to day 20 of pregnancy for 24 h/day until necropsied on day 20. The respective peak-to-peak intensities of the fields were 35.6 μT (sinewave) and 15.0 μT (sawtooth). Each treatment group contained 72 bred females. Control animals were kept under the same conditions without the magnetic field. No adverse effects were seen in the dams. The mean numbers of implantations and living fetuses per litter were statistically significantly increased in the 50-Hz group. There were, however, three total resorptions of litters in dams of the control group, which contributed to the difference in the number of living fetuses. The corrected body-mass gains (gains without uterine content) of dams were similar in all groups. Pregnancy rates, incidences of resorptions. late fetal deaths, and fetal body masses were similar in all groups. The incidence of fetuses with minor skeletal anomalies was statistically significantly increased in both exposed groups. Only one serious malformation (anophthalmia, sawtooth-exposed group) and a few minor visceral malformations were found. In conclusion, the magnetic fields used in this study did not increase the incidence of major malformations or resorptions in Wistar rats. The increased number of skeletal anomalies and implantations we observed indicates, however, that some developmental effects in rats may attend exposure to time-varying magnetic fields. © 1993 Wiley-Liss. Inc.     

Intrauterine growth restriction in rats is associated with hypertension and renal dysfunction in adulthood

Epidemiological studies have produced evidence that unfavorable intrauterine environments during fetal life may lead to adverse outcomes in adulthood. We have previously shown that a low-sodium diet, given to pregnant rats over the last week of gestation, results in intrauterine growth restriction (IUGR). We hypothesize that pups born with IUGR are more susceptible to the development of hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for organ growth and renal morphogenesis. The adults (12 wk) were evaluated for weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone system (RAAS), and renal function; hearts and kidneys underwent a histological examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR fetuses compared with age-matched controls, whereas the kidney-to-body ratio was unchanged. Systolic blood pressure was elevated in both IUGR male and female adults. Plasma aldosterone levels were not correlated with increased plasma renin activity. Moreover, urinary sodium was decreased, whereas plasma urea was elevated in both males and females, and creatinine levels were augmented only in females, suggesting a glomerular filtration impairment in IUGR. In our model of IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure, alteration of the RAAS, and renal dysfunction are observed in adult life. Differences observed between male and female adults suggest the importance of gender in outcomes in adulthood after IUGR.     

Fetal pathology produced by ethylene oxide treatment of the murine zygote

Exposure of female mice to ethylene oxide by inhalation 1 or 6 h after mating produced not only multitemporal death of conceptuses but also high rates of abnormalities among surviving fetuses. In contrast, only marginal effects were observed when females were exposed 9 or 25 h after mating. The abnormalities found among 17 day gestation live fetuses were predominated by hydrops and eye defects, which, together, constitute 54% of all anomalies. Most of the remaining anomalies were distributed among 5 other types: small size, cleft palate, and cardiac, abdominal wall, or extremity and/or tail defects. In a follow-up study, the fetuses of females treated 6 h postmating were examined at 11-15 days gestation and the progression of fetal death and of malformations was studied. Results indicate that the expression of most fetal anomalies does not become apparent until late in gestation. Several of these induced anomalies are similar to common human sporadic birth defects. This new class of experimentally induced fetal anomalies provides a new avenue for investigating zygotic biology and a system for studying the progression of aberrant development.     

The effect of methylmercury on prenatal development and trace metal distribution in pregnant and fetal rats

Methylmercuric chloride (MetHg) at the dose of 2.5 mgHg/kg was administered by gavage every other day to pregnant rats from the sixth to the twentieth day of gestation. On the 21st day of gestation, females were sacrificed to allow the evaluation of embryotoxicity and the taking of analytical material. Copper, zinc, iron, and calcium were determined4 by AAS in brain, liver, kidneys, intestine, whole blood, and spleen of pregnant MetHg-exposed, nonpregnant and pregnant control females, and in fetuses as well as in placenta. Exposure of pregnant rats to MetHg brought about a decrease in the concentration of intestinal iron and calcium compared with control pregnant animals. In whole fetuses where the mother had been exposed to MetHg, the concentrations of calcium and iron were significantly decreased. The skeletal examination showed developmental retardation of fetuses in the MetHg group, which was reflected in enhanced frequency of delayed ossification of the sternebrae, os occipitale, and vertebrae. The copper level in the brains of fetuses from intoxicated mothers was significantly lower and the absolute brain weights were higher than in controls.