Gestational changes in concentrations of selenium and zinc in the porcine fetus and the effects of maternal intake of selenium

The effect of maternal dietary selenium (Se) and gestation on the concentrations of Se and zinc (Zn) in the porcine fetus were determined. Mature gilts were randomly assigned to treatments of either adequate (0.39 ppm Se) or low (0.05 ppm Se) dietary Se. Gilts were bred and fetuses were collected throughout gestation. Concentrations of Se in maternal whole blood and liver decreased during gestation in sows fed the low-Se diet compared to sows fed the Se-supplemented diet. Maternal intake of Se did not affect the concentration of Se in the whole fetus; however, the concentration of Se in fetal liver was decreased in fetuses of sows fed the low-Se diet. Although fetal liver Se decreased in both treatments as gestation progressed, the decrease was greater in liver of fetuses from sows fed the low-Se diet. Dietary Se did not affect concentrations of Zn in maternal whole blood or liver or in the whole fetus and fetal liver. The concentration of Se in fetal liver was lower but the concentration of Zn was greater than in maternal liver when sows were fed the adequate Se diet. These results indicate that maternal intake of Se affects fetal liver Se and newborn piglets have lower liver Se concentrations compared to their dams, regardless of the Se intake of sows during gestation. Thus, the piglet is more susceptible Se deficiency than the sow.     

Teratogenicity of zinc deficiency in the rat: study of the fetal skeleton

Zinc deficiency (ZD) is teratogenic in rats, and fetal skeletal defects are prominent. This study identifies fetal skeletal malformations that affect calcified and non-calcified bone tissue as a result of gestational zinc deficiency in rats, and it assesses the effect of maternal ZD in fetal bone calcification. Pregnant Sprague-Dawley rats (180-250 g) were fed 1) a control diet (76.4 micrograms Zn/g diet) ad libitum (group C), 2) a zinc-deficient diet (0 microgram/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. Fetuses were weighed, examined for external malformations, and stained in toto with a double-staining technique for the study of skeletal malformations. Maternal and fetal tissues were used for Zn, Mg, Ca, and P determinations. Gross external malformations were present in 97% of the ZD fetuses. No external malformations were found in fetuses from groups C and PF. Ninety-one percent of cleared ZD fetuses had multiple skeletal malformations, whereas only 3% of the fetuses of group PF had skeletal defects; no skeletal malformations were found in fetuses from group C. Some of the skeletal malformations described in the ZD fetuses, mainly affecting non-calcified bone, were not mentioned in previous reports, thus stressing the importance of using double-staining techniques. Examination of stained fetuses and counting of ossification centers revealed important calcification defects in ZD fetuses. These effects were confirmed by lower Ca and P concentrations in fetal bone with alteration of the Ca:P ratio.     

Maternal selenium deficiency increases hydrogen peroxide and total lipid peroxides in porcine fetal liver

To investigate the role of selenium (Se) in the developing porcine fetus, prepubertal gilts (n=42) were randomly assigned to either Se-adequate (0.39 ppm Se) or Se-deficient (0.05 ppm Se) gestation diets 6 wk prior to breeding. Maternal and fetal liver was collected at d 30, 45, 70, 90, and 114 of pregnancy. Concentrations of Se in maternal liver decreased during gestation in gilts fed the low-Se diet. The activity of cellular glutathione peroxidase (GPx) was decreased at d 30 and 45 of gestation in liver of gilts fed the low-Se diet. Concentrations of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were greater in liver homogenates from gilts fed the low-Se diet. Within the fetuses, liver Se decreased in those fetuses of gilts fed the low-Se diet. Although the activity of GPx in fetal liver was not affected by the maternal diet, concentrations of H₂O₂ and MDA in fetal liver were greater in fetuses from gilts fed the low-Se diet. Maternal liver GPx activity was approx 12-fold greater than fetal liver GPx activity regardless of dietary treatment. These results indicate that maternal dietary Se intake affects fetal liver Se concentration and feeding a low-Se diet during gestation increases oxidative stress to the fetus, as measured by fetal liver H₂O₂ and MDA.     

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.     

6-Mercaptopurine-induced alterations in mineral metabolism and teratogenesis in the rat

The relationship between 6-mercaptopurine-induced alterations in mineral metabolism and the teratogenic effects of the drug were investigated. Pregnant Sprague-Dawley rats were fed diets containing 4.5, 100, or 1,000 micrograms Zn per 1 g diet. On day 11 of gestation, dams were given intraperitoneal injections of 6-mercaptopurine (27.5 mg/kg). At term, dams fed the 1,000-micrograms Zn per 1 g diet showed fewer drug-induced deleterious effects on reproduction and embryogenesis than did those fed lower levels of zinc. Mineral analysis of maternal and fetal tissues revealed pronounced effects of 6-mercaptopurine on metabolism of zinc, copper, iron, calcium, and magnesium. The results of this study indicate that 6-mercaptopurine teratogenesis may be due in part to drug-induced changes in mineral metabolism.     

Inducibility and amounts of metallothionein as influenced by cadmium and zinc in the developing rat

Information on the accumulation and/or depletion of Zn in metallothionein (MT) of rat fetus, rat pup, and maternal rat liver at various ages was obtained with pregnant rats fed a basal casein diet or this diet plus either 100 ppm Zn or 50 ppm Cd. Rats fed each of the respective diets were sacrificed on 12, 16, and 20 d of gestation and 0, 7, 14, and 28 d post-partum. No Cd was detected in the placenta or fetal tissue and the Cd did not affect the accumulation of Zn in the fetal MT, but it did increase the Zn content in liver MT of the dams. Very little Zn in MT was found on day 12 of gestation, but Zn rapidly increased in MT to a maximum at time of birth. The accumulation of Zn in MT was independent of the diet for the fetuses, but the Zn accumulation in the dam and pup tissues was diet dependent. In order to study age-dependent difference in the inducibility of MT, newborn, 5-week-old, or 24-week-old rats were injected with zinc at the levels of 0, 3, 6, or 9 mg/kg and 5 h later injected with³⁵S-cystine. In rats sacrificed 1 h later, the amount of radioactivity in liver MT demonstrated that this protein in older animals was more readily induced by Zn than in younger animals.     

Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat

Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-(13)C,(2)H(3)-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in the animals fed a methionine-limited diet. Throughout gestation, the pancreas exported homocysteine for methylation within other tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the dams were fed folate- and choline-deficient methionine-restricted diets. This study shows that methyl-deficient diets decrease the remethylation of homocysteine within maternal tissues but that these rates are protected to some extent within fetal tissues.     

Maternal nutrient restriction reduces concentrations of amino acids and polyamines in ovine maternal and fetal plasma and fetal fluids

Amino acids and polyamines are essential for placental and fetal growth, but little is known about their availability in the conceptus in response to maternal undernutrition. We hypothesized that maternal nutrient restriction reduces concentrations of amino acids and polyamines in the ovine conceptus. This hypothesis was tested in nutrient-restricted ewes between Days 28 and 78 (experiment 1) and between Days 28 and 135 (experiment 2) of gestation. In both experiments, ewes were assigned randomly on Day 28 of gestation to a control group fed 100% of National Research Council (NRC) nutrient requirements and to an nutrient-restricted group fed 50% of NRC requirements. Every 7 days beginning on Day 28 of gestation, ewes were weighed and rations adjusted for changes in body weight. On Day 78 of gestation, blood samples were obtained from the uterine artery and umbilical vein for analysis. In experiment 2, nutrient-restricted ewes on Day 78 of gestation either continued to be fed 50% of NRC requirements or were realimented to 100% of NRC requirements until Day 135. Fetal weight was reduced in nutrient-restricted ewes at both Day 78 (32%) and Day 135 (15%) compared with controls. Nutritional restriction markedly reduced (P < 0.05) concentrations of total alpha-amino acids (particularly serine, arginine-family amino acids, and branched-chain amino acids) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids at both mid and late gestation. Realimentation of nutrient-restricted ewes increased (P < 0.05) concentrations of total alpha-amino acids and polyamines in all the measured compartments and prevented intrauterine growth retardation. These novel findings demonstrate that 50% global nutrient restriction decreases concentrations of amino acids and polyamines in the ovine conceptus that could adversely impact key fetal functions. The results have important implications for understanding the mechanisms responsible for both intrauterine growth retardation and developmental origins of adult disease.     

Maternal omega-3 fatty acids maintained positive maternal lipids and cytokines profile,and improved pregnancy outcomes of C57BL/6 mice

Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome.     

Prenatal Zinc Deficiency: Influence on Heart Morphology and Distribution of Key Heart Proteins in a Rat Model

The etiology of congenital heart disease is multifactorial, with genetics and nutritional deficiencies recognized as causative agents. Maternal zinc (Zn) deficiency is associated with an increased risk for fetal heart malformations; however, the contributing mechanisms have yet to be identified. In this study, we fed pregnant rats a Zn-adequate diet (ZnA), a Zn-deficient (ZnD), or a restricted amount of Zn adequate diet (RF) beginning on gestation day (GD) 4.5, to examine whether increased cell death and changes in cardiac neural crest cells (NCC) play a role in Zn deficiency-induced heart defects. Fetuses were collected on GD 13.5, 15.5, and 18.5 and processed for GATA-4, FOG-2, connexin-43 (Cx43), HNK-1, smooth muscle α-actin (SMA) and cleaved caspase-3 protein expression. Fetuses from ZnA-fed dams showed normal heart development, whereas fetuses from dams fed with the ZnD diet exhibited a variety of heart anomalies, particularly in the region of the outflow tract. HNK-1 expression was lower than normal in the hearts of GD13.5 and 15.5 ZnD fetuses, particularly in the right atrium and in the distal tip of the interventricular septum. Conversely, Cx43 immunoreactivity was increased throughout the heart in fetuses from ZnD dams compared to fetuses from control dams. The distribution and intensity of expression of SMA, GATA-4, FOG-2, and markers of apoptosis were similar among the three groups. We propose that Zn deficiency induced alterations in the distribution of Cx43 and HNK-1 in fetal hearts contribute to the occurrence of the developmental heart anomalies.     

Influence of maternal mineral deficiency on the hepatic metallothionein and zinc in newborn rats

The effects of maternal Zn, Cu, or Fe deficiencies during late gestation on hepatic levels of metals and metallothionein (MT) and the binding of Zn and Cu to protein fractions were investigated in newborn rats. Timed pregnant rats were fed one of the following diets: Zn deficient (Zn-D), Cu-D, Fe-D, or control from day 12 of gestation until birth. The specific nutritional deficiency status of the dams was confirmed by low plasma levels of the deficient metal. Livers from pups were analyzed for MT, metal content, and metal-protein binding. Maternal Zn-D resulted in a greater than 50% reduction of hepatic MT levels in pups, whereas Cu-D and Fe-D had no significant effects. Pups in each deficient group showed a significant decrease in the hepatic levels of the respective metals. Fractionation of hepatic cytosols from the pups by Sephadex G-75 gel filtration showed that in both Fe-D and Cu-D pups the respective metals were depleted from the high molecular weight protein fraction, whereas in Zn-D pups the Zn was depleted mainly from the MT fraction (Ve/V0 approximately 2). Incorporation of [35S] cysteine into MT fractions was significantly lower in Zn-D pups as compared with control pups. These results indicate that there is a specific effect of the maternal Zn-D on the hepatic storage of Zn as MT in newborn rats.     

Relationship of dietary zinc to 6-mercaptopurine teratogenesis and DNA metabolism in the rat

The possible interaction between the level of maternal dietary zinc and the teratogenic activity of 6-mercaptopurine was investigated. Pregnant Sprague-Dawley rats were fed diets containing 9,100 or 1,000 ppm zinc from day zero of pregnancy and were given a single intraperitoneal injection of 6-MP (55mg/kg) on day 11. At term, females in the group fed 1,000 ppm zinc (a high intake) showed less pronounced effects on reproduction and embryogenesis than did those fed 9 ppm (marginally deficient) or 100 ppm (normal) zinc. Embryos examined on day 12 of gestation had similar concentrations of protein and RNA; however, the DNA content was lower and the incorporation of 3H-thymidine was greater in the drug treated groups than in non-drug treated controls. These results indicate that 6-mercaptopurine is acting to alter embryonic DNA metabolism and that high levesl of dietary zinc may ameliorate some of the deleterious effects of this drug on embryonic and maternal toxicity.     

Changes in hypothalamic noradrenergic systems during the anorexia of zinc deficiency

Pregnant Wistar rats fed control and Zn-deficient diets received daily oral doses of 0, 100, and 300 mg/kg sodium valproate from d 16 to 20 of gestation. Only the highest valproate doses induced a small reduction in fetal body weight in the normally fed group. Zinc deficiency caused a drastic reduction in maternal and only a small reduction in fetal serum Zn concentrations. Valproate treatment had no effect on maternal and fetal serum Zn concentrations. Valproate reduced fetal liver Zn content only in the normally fed group. The reduction of liver Zn content resulted from the reduction of Zn-metallothionein. Valproate did not affect total Zn and Zn-metallothionein in kidneys. Three percent of the Zn-deficient fetuses developed hydronephrosis and hydrops. Valproate treatment drastically enhanced the occurrence of fetal hydronephrosis and hydrops. Valproate induced fetal liver necroses, independent of Zn nutrition.     

Zinc, copper, and iron metabolism during porcine fetal development

Zinc, copper, and iron levels in maternal and fetal pig tissues and fluids were measured starting on d 30 of gestation and continuing to term (d 114) at 10-d intervals. Fetal hematocrit increased from a low of 19% on d 30 to 32% by d 50, after which it remained above 30% to term. Amniotic fluid zinc, copper, and iron all reached maximal levels by d 60 of gestation. Maternal serum zinc levels fluctuated little during gestation, but fetal serum zinc concentration was significantly elevated above maternal levels during the second trimester. Fetal serum copper levels were significantly lower than maternal values throughout gestation and this was also the case for ceruloplasmin oxidase activity. Maternal serum iron reached its lowest level by d 80 of gestation when rate of transfer of iron to the developing fetuses was high. Fetal serum iron declined throughout gestation, reaching its lowest level on d 100. In general, fetal liver concentrations of zinc, copper, and iron were higher than the corresponding maternal values throughout gestation. Distinct increases were noted for fetal hepatic zinc and copper concentrations during the second trimester of pregnancy and these were accompanied by increases in cytosolic and metallothionein-bound zinc and copper levels. Maternal hepatic iron declined during the second trimester, reaching its lowest point on d 80, indicative of the shunting of maternal iron reserves to fetal tissues. Fetal kidney metal levels did not demonstrate any distinctive developmental patterns with respect to zinc, copper, or iron concentrations, but a general accumulation of each metal was observed as gestation progressed. The results of this study highlight some of the distinct changes occurring in the metabolism of zinc, copper, and iron in both maternal and fetal tissues and fluids during gestation in the pig. Mention of a trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other suitable products.     

Effect of dietary copper and zinc levels on tissue copper,zinc, and iron in male rats

The interaction between dietary copper and zinc as determined by tissue concentrations of trace elements was investigated in male Sprague-Dawley rats. Animals were fed diets in a factorial design with two levels of copper (0.5, 5 μg/g) and five levels of zinc (1, 4.5, 10, 100, 1000 μg/g) for 42 d. In rats fed the low copper diet, as dietary zinc concentration increased, the level of copper decreased in brain, testis, spleen, heart, liver, and intestine. There was no significant effect of dietary copper on tissue zinc levels. In the zinc-deficient groups, the level of iron was higher in most tissues than in tissues from controls (5 μg Cu, 100 μg Zn/g diet). In the copper-deficient groups, iron concentration was higher than control values only in the liver. These data show that dietary zinc affected tissue copper levels primarily when dietary copper was deficient, that dietary copper had no effect on tissue zinc, and that both zinc deficiency and copper deficiency affected tissue iron levels.     

Relationship between plasma zinc, angiotensin-converting enzyme, alkaline phosphatase and onset of symptoms of zinc deficiency in the rat

Recent evidence suggests that changes in plasma zinc concentration may play a central role in the development of early lesions of zinc deficiency. The aim of the following work was to better understand events occurring in plasma during the onset of zinc deficiency, and to investigate biochemical mechanisms by which plasma zinc may exert its effects. Fifty male weanling rats of 90 g weight were allocated to five treatment groups of ten rats each. Treatments were: 1, zinc deficient, mixed diet (1-2 mg Zn per kg): 2, zinc deficient, self-select diet; 3, zinc repleted; 4, control, pair fed; 5, control, ad libitum fed. With the exception of treatment 1, which consisted of a 25% casein diet, all rats were offered protein as a separate component of the diet. Control rats received zinc in the drinking water (100 mg l-1). The sequence of events following initiation of zinc deficiency were: reduced plasma zinc concentration (2 days), reduced plasma angiotensin-converting enzyme and alkaline phosphatase activities (3-4 days), reduced feed intake and growth (5-6 days) and reduced percentage protein intake (12 days). Plasma zinc concentration in the deficient rats was inversely correlated with the growth rate of the rat over the previous 24 h. Zinc repletion resulted in marked overshoot in plasma zinc concentration (300%) and converting-enzyme activity (150%) within 24 h, but a return to normal within 72 h. Alkaline phosphatase activity responded likewise, albeit more slowly. Protein self selection had no effect on the manifestations of zinc deficiency, although reduced protein intake was associated with lower plasma zinc concentration. The results provide evidence of a role for plasma zinc in the development of early clinical signs of zinc deficiency, possibly acting biochemically through reduced activity of zinc-dependent peptidases such as angiotensin-converting enzyme.     

Fetal leptin is a signal of fat mass independent of maternal nutrition in ewes fed at or above maintenance energy requirements

In adults, circulating leptin concentrations are dependent on body fat content and on current nutritional status. However, the relationships among maternal nutrient intake, fetal adiposity, and circulating leptin concentrations before birth are unknown. We investigated the effects of an increase in nutrient intake in the pregnant ewe on fetal adiposity and plasma leptin concentrations during late gestation. Between 115 and 139-141 days gestation (term = 147 +/- 3 days gestation), ewes were fed a diet calculated to provide either maintenance (control, n = 6) or approximately 155% of maintenance requirements (well-fed, n = 8). The fetal fat depots (perirenal and interscapular) were dissected, and the relative proportion of unilocular and multilocular adipocytes in each depot was determined. Maternal plasma glucose and leptin concentrations were significantly increased in well-fed ewes. Fetal plasma glucose concentrations were also higher in the well-fed group (115-139 days gestation: control, 1.65 +/- 0.14 mmol/L; well-fed, 2.00 +/- 0.14 mmol/L; F = 5.76, P < 0.04). There was no effect of increasing maternal feed intake on total fat mass, the relative mass of unilocular fat, or fetal plasma leptin concentrations (115-139 days gestation: control, 5.2 +/- 0.8 ng/ml; well-fed, 4.7 +/- 0.7 ng/ml). However, in both the control and well-fed groups fetal plasma leptin concentrations (y) were positively correlated with the relative mass of unilocular fat (x): y = 1.51x + 1.70; (R = 0.76, P < 0.01). Thus, fetal leptin may play a role as a signal of unilocular fat mass in the fetus when maternal nutrient intake is at or above maintenance requirements.     

Regulation of the ontogeny of rat liver metallothionein mRNA by zinc

To investigate the role of metals in the regulation of the ontogenic expression of rat liver metallothionein (MT) mRNA, the concentrations of zinc, MT and MT mRNA were determined in livers of fetal and newborn rats from dams which were fed with a control or zinc-deficient or copper-deficient or iron-deficient diet from day 12 of gestation. The liver samples were analyzed for MT-mRNA levels using a mouse MT-I cRNA probe. Although the newborn hepatic levels of each metal (zinc or copper or iron) was specifically reduced corresponding to the respective mineral deficiencies, the hepatic concentrations of total MT and MT-I mRNA were significantly decreased only in pups born from zinc-deficient dams. Injection of the zinc-deficient newborn pups with 20 mg Zn as ZnSO4/kg restored with MT-I mRNA levels to slightly above control values within 5 h of injection. The hepatic zinc, MT and MT-I mRNA levels were observed to increase significantly in control fetal rat liver on days 17-21 of gestation but there were little changes in either zinc or MT in fetal livers from zinc-deficient dams during the late gestational period. The MT-I mRNA level also did not show an increase on days 18 and 20 of gestation in zinc-deficient fetal liver as compared to controls. These results demonstrate a direct role of zinc in hepatic MT gene expression in rat liver during late gestation. Immunohistochemical localization of MT using a specific antibody to rat liver MT showed that the staining for MT in zinc-deficient pup liver was mainly in the cytosol in contrast to the significant nuclear MT staining observed in control newborn rat liver. The results suggest that maternal zinc deficiency has a marked effect not only in decreasing the levels of hepatic MT and MT-I mRNA but also in the localization of MT in newborn rat liver.     

Effect of maternal thyroparathyroidectomy before gestation on fetal development in rats.

Female rats were thyroparathyroidectomized (TPTX) at 24 (immature), 40 (pubertal) and 75 (matured) days of age, at least 21 days before mating. Thyroxine (2.5 microgram/kg) or parathyroid hormone (150 USP units/kg x 2) was replaced in two TPTX groups. Thyroxine deficient groups of all ages had reduced body weight, litter size and serum thyroxine and calcium level. Fetal weights at 20 days of gestation in all thyroxine deficient groups were significantly reduced but placental weight was generally increased. Maternal serum thyroxine and fetal weight was positively related when all groups were taken together, but maternal serum calcium and fetal weight was not related. There were no significant differences in gross, visceral or skeletal anomalies in the fetuses in any group.