Effects of maternal marginal zinc deficiency on myelin protein profiles in the suckling rat and infant rhesus monkey

In the current study, the effects of marginal Zn deficiency on myelin protein profiles in neonatal rats and rhesus monkeys were investigated. Following mating, rats were fed a Zn-adequate diet,ad libitum (50 μg Zn/g; 50 Zn AL), or a marginal Zn diet (10 μg Zn/g) from day 0 (10 Zn d0) or day 14 (10 Zn d14) of gestation to day 20 postnatal. An additional group of dams was restricted-fed the control diet to the food intake of the 10 Zn d0 group (50 Zn RF). Day 20 pup plasma and liver Zn concentrations in the 10 Zn groups were lower than in the 50 Zn groups. In a parallel experiment, rhesus monkeys were fed a Zn-adequatead libitum diet (100 μg Zn/g) or a marginal Zn diet (4 μg Zn/g diet; MZD) throughout gestation and lactation. Day 30 monkey infant plasma and liver Zn levels were similar in the MZD and control groups. Rat brain and monkey brain cortex weights were similar among the dietary groups. The amount of myelin recovered (mg protein/g brain) from day 20 rat pups from the 10 Zn groups was lower than that recovered from the 50 Zn rat pups. Myelin recovery from the MZD and control monkey infants was similar. When myelin protein profiles were characterized, it was found that the percentages of high-molecular-weight (HMW) proteins and Wolfgram protein were higher, whereas the percentages of small and large basic proteins were lower in myelin from the 10 Zn d0 and 50 Zn RF pups compared to the distribution in the 50 Zn AL rat pups. Results for the 10 Zn d0 and 10 Zn d14 pups were similar for all of the parameters studied. The percentage of HMW proteins was higher and that of basic protein lower in myelin from MZD monkey infants compared to the percentage of these proteins in myelin from controls. Although the interpretation of the rat data is complicated because of the anorexia associated with the Zn deficiency, the observed changes in monkey myelin protein profiles provide strong evidence that maternal Zn deficiency affects myelination in the offspring.     

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.     

Influence of the pineal gland on testicular function in offspring of pinealectomized rats

Female Sprague-Dawley rats exposed to a short (6L:18D) photoperiod from 21 days of age were mated when they reached 55 days of age. On Day 2 of gestation animals were pinealectomized or sham-operated. On Day 5 after birth male pups of the two groups of dams were either pinealectomized or sham-operated. They were killed at 42 and 49 days of age. In offspring born to sham-operated dams and in those born to pinealectomized mothers, neonatal pineal ablation resulted in increased testicular testosterone and androstenedione content. In sham-operated and neonatally pinealectomized rats removal of the maternal pineal gland induced a decrease in testicular testosterone and androstenedione content. In contrast, after maternal pinealectomy there was a decrease in plasma testosterone and dihydrotestosterone values and testicular dihydrotestosterone content in sham-operated rats but not in those neonatally pinealectomized. We conclude that (1) the pineal glands of the mother and offspring are required to maintain normal testicular testosterone and androstenedione content in the rat, and (2) the pineal of the offspring influences the inhibitory effects of maternal pinealectomy on testicular dihydrotestosterone content and on plasma testosterone and dihydrotestosterone concentration in the offspring.     

Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups

In the present study, two groups of pregnant female rats were submitted to food restriction (24 h fast versus 24 h diet intake) from the 14th day of pregnancy until either the 14th day (group B) or the 4th day after parturition (group C). All pups and their mothers were sacrificed on day 14 after delivery. The body weight of the 14-day-old pups (group B) was 46% less than the controls (group A). Free thyroxine and free triiodothyronine levels in the plasma were reduced by 44 and 16% in pups and by 20 and 36% in their mothers, respectively. These reductions were correlated with a decrease in thyroid iodine content of the pups (-50%) and their mothers (-24%). Radioiodine uptake (131I) by the thyroid gland of pups was significantly increased by 27%. Plasma TSH levels were decreased by 38% in pups and by 44% in dams. Morphological changes in thyroid glands were observed in energy restricted dams and in their pups. Some of follicles in pups were empty. Moroever in dams, we noted the presence of peripheral resorbed vacuoles, sign of thyroid hyperactivity. After a refeeding (group C) period of ten days, total recovery occurred in plasma thyroid hormone levels (FT4 and FT3) and in thyroid iodine contents of pups in spite of a partial recovery of body weights and plasma TSH levels. In dams, a partial recovery occurred in plasma thyroid hormone levels in spite of total recovery in thyroid iodine contents, while plasma TSH levels exceeded control values. A significant amelioration in thyroid histological aspects was observed in pups and their dams.     

Correlation of Calcium and Magnesium Levels in the Biological Samples of Different Types of Acute Leukemia Children

We aimed to investigate the effect of maternal exposure to NaF on mandibular bone microarchitecture and phosphocalcic plasma parameters of the offspring. For this purpose, 10-, 15-, and 21-day-old pups (n?=?6–8 per group) from two groups of mothers, control and NaF 50mg/L treated dams, were used. Plasma calcium (Ca) and phosphorus (P) levels and alkaline phosphatase activity (ALP) were measured. Fluoride concentration (F^?) in bone and in stomach content was measured using potentiometry after isothermal distillation. Morphometric, histological, and histomorphometric analyses of the jaw bones were performed. Plasma Ca and P levels and ALP activity increased in 10-day and decreased in 21-day-old pups from NaF-treated mothers. Fluoride concentration in stomach content samples of 15- and 21-day-old nursing pups from mothers exposed to NaF in their drinking water was higher compared to that observed in control dam offspring. Mandibular F^? content was higher in 21-day-old pups born to F^?-exposed dams compared to those observed in age-matched control pups. Mandibular area increased in 21-day-old pups born to treated mothers as compared to controls. Mandibular bone volume BV/TV (%) was higher in offspring from NaF-exposed dams than in controls at all the studied times. The increase in bone volume after exposure to F^? was concomitant with the increase in trabecular thickness and the decrease in trabecular separation. Altogether, our results showed that exposure to NaF during gestation and lactation increased mandibular area and bone volume of pups, with concomitant changes in phosphocalcic parameters associated with the bone modeling process.     

Hematological and serum biochemical changes with age in term fetuses, offspring and dams in normal Sprague-Dawley rats]

Hematological and serum biochemical values of dams and offspring of Sprague-Dawley rats were measured during late gestation, lactation and postweaning. In dams, slightly low erythrocytic parameters, high platelets and high frequency of neutrophils were seen after parturition although WBC showed no marked changes. On Day 20 of gestation, glucose and triglycerides were extremely high and TP and albumin were low. These changes may be attributed to pregnancy or parturition. In fetuses on Day 20 of gestation and offspring immediately after birth, erythrocytes showed anisocytosis, polychromasia, basophilic stipplings and Howell-Jolly bodies and erythroblasts were found. RBC was low. MCV and MCH were extremely high, compared to adult erythrocyte levels. Hemoglobin and hematocrit slightly decreased before weaning. RBC, hemoglobin and hematocrit increased with age and reached adult levels by Day 56. MCV and MCH values decreased, towards adult levels, until weaning. Platelets rapidly increased and reached adult levels before weaning. WBC increased after birth having higher counts in males than in females on Day 35 and thereafter. Glucose, TP and albumin increased with age and reached adult levels by Day 28. ALP was high in fetuses and changed with age having two peaks similar to those reported in man. Cholesterols gradually increased after birth and had a peak on Day 14. Urea nitrogen, inorganic phosphorus and calcium were slightly high in fetuses and preweaned offspring. Potassium was high in fetuses but no age-related trends were seen in offspring.     

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.     

Oxidative stress and thyroid impairment after gibberellic acid treatment in pregnant and lactating rats and their offspring

Gibberellic acid (GA?) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA? on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA? in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA?-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT? and FT? levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA?-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA? treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny.     

Cardiac cytochrome-c oxidase deficiency occurs during late postnatal development in progeny of copper-deficient rats

Although cytochrome-c oxidase (CCO) is a copper-dependent enzyme, the effect of maternal copper deficiency on the expression of CCO activity during postnatal development of the neonatal rat heart has not been investigated extensively. Here, we show that CCO activity in heart mitochondria isolated from neonates of copper-deficient dams did not exhibit significant reductions until postnatal days (PND) 15 and 21. In addition, immunoblot analysis indicated that the CCO subunit (Cox-1) was reduced on postnatal Days 10 and 21, and that Cox-4 was reduced on PND 21 in heart mitochondria of the neonates from copper-deficient dams. These findings indicate that the impairment of CCO activity in neonatal heart by maternal copper deficiency occurs late in the postnatal heart development. Furthermore, the concurrent reductions in Cox-1 and Cox-4 suggest that the impaired CCO activity reflects a CCO deficiency in heart mitochondria. CCO activity and Cox-1 in heart mitochondria were not fully restored by 6 weeks of postweaning copper repletion in the pups of copper-deficient dams. This indicates that prolonged maternal intake of moderately low dietary copper produces CCO deficiency in cardiac mitochondria of neonates during late postnatal heart development, after terminal differentiation of cardiomyocytes occurs. The resistance of CCO deficiency to repair by dietary copper supplementation may be related to the relatively slow turnover of the affected mitochondria in the terminally differentiated heart.     

Precocious induction of hepatic glucokinase and malic enzyme in artificially reared rat pups fed a high-carbohydrate diet

Glucokinase and NADP:malate dehydrogenase (malic enzyme) first appear in liver when rat pups are weaned from milk which is high in fat to lab chow which is high in carbohydrate. To examine the influence of diet during the early neonatal period, before developmental changes in the circulating concentrations of thyroid and adrenocortical hormones occur, high-carbohydrate formula (56% of calories from carbohydrate), isocaloric and isonitrogenous with rat milk, was intermittently infused via gastrostomy starting on the second day of life. Pups had no further access to their dams. Body weights attained by these pups were at least 90% of those attained by mother-fed pups, which served as controls. In artificially reared rats fed the high-carbohydrate formula, on Day 4, glucokinase and malic enzyme were 30 and 18% of adult activity, respectively; on Day 10, glucokinase and malic enzyme were 71 and 96% of adult activity, respectively. On Days 4 and 10 glucose-6-phosphate dehydrogenase was elevated four- to fivefold in pups fed the high-carbohydrate formula compared to mother-fed pups. A second isocaloric formula, with 22% of calories from carbohydrate but low in protein, resulted in intermediate levels of all three enzymes on Day 10. Pups fed the high-carbohydrate formula has plasma insulin concentrations four- to fivefold greater than mother-fed pups on both Days 4 and 10. Triiodothyronine administration (1 microgram/g body wt) on Day 1 enhanced the induction of malic enzyme but not glucokinase on Day 4 in pups fed the high-carbohydrate formula. The results demonstrate that neonatal rat liver is competent to respond to high carbohydrate intake by induction of glucokinase and malic enzyme.     

Multiple mechanisms account for lower plasma iron in young copper deficient rats

Copper deficiency lowers brain copper and iron during development. The reduced iron content could be due to hypoferremia. Experiments were conducted to evaluate plasma iron and “ferroxidase” hypotheses by determining copper and iron status of Holtzman albino rats following gestational/lactational copper deficiency. Copper deficient (Cu−) dams on treatment for 5 weeks, two of gestation and three of lactation, had markedly lower copper content of milk and mammary tissue, and lower milk iron. Newborn pups from Cu− dams had lower copper and iron concentrations. Compared to Cu+ pups, Cu− pups, analyzed between postnatal age (P) 0 and P26, were smaller, anemic, had lower plasma iron, cardiac hypertrophy, and near zero ceruloplasmin activity. Liver copper in Cu+ pups increased then decreased during development and major reductions were evident in Cu− pups. Liver iron in Cu+ pups decreased with age while nursing but increased after eating solid food. Liver iron was lower in Cu− pups at P0 and P13 and normal at P20 and P26. Small intestinal copper decreased with age in Cu+ pups and was lower in Cu− pups. Intestinal iron levels in Cu− pups were higher than Cu+ pups postweaning in some experiments. Reduction in plasma iron in Cu− pups is likely due to a decreased “ferroxidase” function leading to lower placental iron transport, a lower milk iron diet, and partial block in iron uptake from intestine but is not due to failure to mobilize hepatic iron, in contrast to older rats eating diet with adequate iron.     

Developmental variation of the diaphragm and liver in Fischer 344 rats

The nature and frequency of a developmental variation of the diaphragm and liver in Fischer 344 rats are described. Totals of 20, 98 and 55 (25 for caesarean-sectioning and 30 for natural delivery) mated female rats were used for Experiments 1, 2, and 3, respectively. Each rat was intubated (gavage) with either an aqueous suspension of 0.2% METHOCEL, 0.25% methyl cellulose, or distilled water as a single daily dose from days 6 through 15 (inclusive) of gestation. On the 20th day of gestation, a caesarean-section was performed, and the uterine contents of each rat were examined. A gross necropsy was performed on the pups of 30 mated female rats on day 21 postpartum. The visceral examinations conducted on these fetuses and pups included an evaluation of a developmental variation in the diaphragm and liver. The variation consisted of a thin fibrous central tendon of the diaphragm with an area of liver (0.5-3 mm diameter) that protruded within the thin central tendon of the diaphragm. The incidence (mean % of fetuses affected per litter) of the diaphragm/liver developmental variation was 9% and 11% for METHOCEL- and water-treated groups, respectively. A thin central tendon was present in the diaphragm of all fetuses of methyl cellulose-treated dams; these fetuses did not have a raised area of the liver present within the diaphragm's central tendon. However, in a few weaned pups of the Fischer 344 rats in this study, liver protruded within the central tendon of the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developmental toxicity of the HIV-protease inhibitor indinavir in rats

BACKGROUND: Indinavir is an antiviral agent used for the treatment of HIV infection. We studied its developmental toxicity in rats. METHODS: Pregnant animals were treated orally with 500 mg indinavir/kg body weight (bw) from day 6 to 15 of gestation (once daily) or from day 9 to 11 (twice daily). Fetuses were evaluated for external and skeletal anomalies on day 21 of gestation. In addition, 19 rats were treated from day 9 of gestation to day 24 postnatally with 500 mg indinavir/kg bw once daily; a control group of 17 rats was treated with the vehicle accordingly. Developmental landmarks were recorded. Sixteen offspring each were studied on postnatal days 7, 14, 21, and 35 for hepatic enzyme activity. Liver tissue was examined by electron microscopy. RESULTS: Fetal examination on day 21 of pregnancy showed no treatment-related effects on number, weight, and viability of the fetuses; however, an increased incidence was noted in the supernumerary ribs and variations of the vertebral ossification centers in both indinavir-treated groups. Postnatal evaluation showed delayed fur development, eye opening, and descensus testis. The most striking finding was unilateral anophthalmia, observed in 7 pups (3%) from 2 out of 19 litters exposed to indinavir, but not in controls. Only minor changes in hepatic monooxygenase activities occurred in dams. Electron microscopy of liver samples showed hepatocellular inclusions of lipids and myelin figure-like structures in maternal livers and infiltration with granulocytes in offspring livers. CONCLUSIONS: Further studies on reproductive toxicity, including combinations of three or more antiretroviral agents as used therapeutically, are needed to determine the hazards of such a treatment.     

Carnitine depletion in rat pups from mothers given mildronate: a model of carnitine deficiency in late fetal and neonatal life

Mildronate (3-(2,2,2,-trimethylhydrazinium)propionate), is a butyrobetaine analogue that is known to inhibit gamma-butyrobetaine hydroxylase, the enzyme catalyzing the last step of carnitine biosynthesis. When administered to adult rats it determines a systemic carnitine deficiency and may therefore serve as an animal model for human carnitine depletion. The aim of this study was to evaluate the effect of mildronate administration to pregnant and lactating rats on tissue carnitine concentrations in 4- and 13-day-old rat pups. At 14 days of gestation female rats began to receive mildronate in the diet (200 mg/kg/d) and this continued for entire lactation period. Mildronate treatment determined a large reduction of carnitine levels in the milk of lactating dams. Because organ carnitine concentrations in neonatal rats are directly related to dietary supply, pups from mildronate group had significantly depleted levels of total carnitine in serum, heart, liver, muscle, brain and pancreas relative to controls, at 4 and 13 days of age. Correspondingly, an increase in triglyceride levels was observed in liver, heart and muscle of mildronate pups. This is in agreement with a reduction of basal rate of oxidation of [U-(14)C]-palmitate to (14)CO(2) and (14)C-acid-soluble products observed in liver homogenates from carnitine-deficient pups. All functional and biochemical modifications were compatible with a carnitine deficiency status. In conclusion our results describe a model of carnitine depletion in pups, suitable for the investigation of carnitine deficiency in fetal-neonatal nutrition, without any concomitant mildronate-mediated metabolic alterations.     

Myometrial adenylyl cyclase protein decreases on the last day of pregnancy in the rat

To determine whether gestation-related changes in responsiveness of the rat uterus to beta-adrenergic agonists are mediated at the level of adenylyl cyclase, we measured myometrial adenylyl cyclase activity and protein quantities during pregnancy and labor. In rat myometrial membranes, basal adenylyl cyclase activity increased from the nonpregnant state to mid (Days 12-14) and then late (Days 18-20) gestation and then decreased intrapartum (Day 22). Stimulated adenylyl cyclase activity, at the level of the beta-adrenergic receptor (isoproterenol, 10(-4) M), the G protein (GTP, 10(-5) M), or the adenylyl cyclase enzyme (MnCl(2), 20 mM), was similarly altered during gestation. Total adenylyl cyclase protein was quantified by [(3)H]forskolin binding assay in myometrial membranes from nonpregnant and pregnant (Day 14, Day 20, Day 21, and intrapartum Day 22) rats. Adenylyl cyclase protein increased progressively from nonpregnant rats to pregnant rats at mid (Day 14) and late (Day 20) gestation, but it decreased abruptly to nonpregnant levels on Day 21, the day before parturition, and remained at similar levels on Day 22 (intrapartum). The gestation-related increase in expression of myometrial adenylyl cyclase protein may facilitate uterine quiescence during pregnancy, and the abrupt decrease of adenylyl cyclase protein on the last day of pregnancy may be a contributing mechanism for the initiation of labor.     

Effects of maternal ethanol consumption during pregnancy or lactation on intestinal absorption of folic acid in suckling rats

A fostering/crossfostering analysis of the effects of maternal ethanol exposure on jejunal and ileal folate absorption was performed. Male and female rats were randomized into two groups. In the first group, ethanol-treated rats received ad libitum 5, 10 and 15% ethanol in the drinking fluid during three successive weeks. A consumption of 20% was maintained in this group for 5 additional weeks. Ethanol-treated rats were mated. Group 2 served as the control. To study the effect of chronic alcoholism during lactation or gestation separately, at birth (2nd day postpartum) control newborns were cross-fostered to ethanol dams (EG), and the pups issued from the ethanol treated mothers were cross-fostered to control dams (CG). Thus, three experimental groups of pups were formed: (1) control pups receiving no treatment during gestation and lactation (CG); (2) pups exposed to ethanol only during gestation (GG); and (3) pups exposed to ethanol only during lactation (LG). At 21 days postpartum the jejunal and distal ileum folate absorption was determined in the offspring rats by a perfusion technique. Milk folic acid levels were determined by an immunoluminometric assay. The results showed an increase in jejunal folic acid absorption in offsprings exposed to ethanol only during the lactation period (LG). However, in pups exposed to ethanol only during the gestation period (GG), the jejunal folic acid absorption was significantly increased only at concentrations of 0.25, 0.5 and 2.5 microM. No free folic acid absorption occurred in the distal ileum of control pups (CG) at day 21 at all assayed concentrations but in offsprings exposed to ethanol only during the gestation or lactation periods absorption did take place. Pups exposed to ethanol during the gestation period (GG) showed decreased values in ileum folic acid absorption at the lowest assayed concentration (0.25 microM) compared to values obtained for pups exposed to ethanol only during lactation (LG). Milk folic acid levels were significantly decreased in the ethanol-fed dams on day 21 of lactation. These results indicate that exposure of rats to ethanol during the lactation period affects more severely postnatal development of intestinal functions than ethanol exposure only during gestation. In summary, both the exposure to ethanol itself and the decrease in folic acid intake caused alterations in the function of the intestinal mucosa in the offspring, which in turn altered absorption time and development. However, the present results do not explain how ethanol stimulated intestinal absorption of folic acid in pups exposed to ethanol during the gestation or lactation periods. Further studies are needed.     

Biotinidase deficiency: Novel mutations in Algerian patients

Biotinidase deficiency is an autosomal recessive disorder of biotin metabolism leading to varying degrees of neurologic and cutaneous symptoms when untreated. In the present study, we report the clinical features and the molecular investigation of biotinidase deficiency in four unrelated consanguineous Algerian families including five patients with profound biotinidase deficiency and one child characterized as partial biotinidase deficiency. Mutation analysis revealed three novel mutations, c.del631C and c.1557T>G within exon 4 and c.324-325insTA in exon 3. Since newborn screening is not available in Algeria, cascade screening in affected families would be very helpful to identify at risk individuals.     

Suckling in rats extended by continuous living with dams and their preweanling litters

To evaluate the role of the dam and littermates in weaning, rats were separated from their biological mothers, beginning at 21 days of age, and housed with a succession of dams and their 16–21-day-old litters. Suckling persistence was evaluated every 5 days until rats reached 70 days of age or no longer suckled. Rats housed in such a preweaning environment continued to suckle well past the normal age of weaning. Specifically, 50% suckled until day 55, and 15% suckled until they were 70 days of age and sexually active. In addition, the interactions among three dams and their litters composed of 16–21-day-old pups and a 45–50-day-old rat that had been housed with similar litters were analysed from time-lapse video-recordings. Experimental rats routinely suckled in the nest and withdrew milk from the dam, but did so only when most of the younger pups had already attached. These data suggest that the maternal and social milieu plays a role in the maintenance of suckling behaviour.     

Prenatal blockade of estradiol synthesis impairs respiratory and metabolic responses to hypoxia in newborn and adult rats

We tested the hypothesis that estradiol modifies respiratory control in pregnant rats and participates in the development of respiratory chemoreflexes in fetuses. Pregnant rats (n = 12) received daily subcutaneous injections of vehicle (Veh, n = 6) or 4-androsten-4-ol-3,17-dione acetate (ATD; inhibitor of estradiol synthesis; n = 6; 5 mg/day in vehicle) from gestational day 16 (G16) to delivery. Baseline ventilation (whole body plethysmography) and metabolic rate [oxygen consumption (Vo(2))] were determined at G14 and G20, in pups [on postnatal day 3 (P3) and P20] and in adult rats (on P70) born to Veh- or ATD-treated mothers. Hypoxic chemoreflex was assessed in P3 rats by acute exposure to 60% O(2) and in P20 or P70 rats by moderate hypoxia (12% O(2), 30 min). ATD treatment reduced circulating estradiol in pregnant dams at G20 without producing changes in the circulating level of estradiol precursors (testosterone and androstenedione). ATD-treated dams showed impaired respiratory adjustment to late gestation. Pups born to ATD mothers had higher resting Vo(2) (+23% at P3, +21% at P20), respiratory frequency (+15% at P3, +12% at P20), and minute ventilation (+11% at P3, +18% at P20) than pups from Veh mothers. Respiratory decrease during acute hyperoxic exposure at P3 was -9.7% in Veh (P < 0.05 vs. room air) and only -2.6% (P = not significant) in ATD pups. In P20 ATD rats, hypoxic ventilatory response was attenuated compared with Veh. In P20 and P70 rats, the drop of Vo(2) in hypoxia (-31% in P70, P < 0.0001) was not observed in ATD rats. We conclude that estradiol secreted during late gestation is necessary for respiratory adjustment to pregnancy and is required for adequate development of respiratory and metabolic control in the offspring.     

Effect of maternal iron deficiency on GABA shunt pathway of developing rat brain

Iron deficiency during pregnancy and lactation (35 mg iron/kg diet) produced a significant reduction in liver nonheme iron in dams as well as in fetus and young ones. The body, liver and brain weights of fetus, new-born, and developing pups remained unaffected. However, the body weight and PCV were reduced only in 21-day-old pups. The enzyme activities of GDH, GAD, GABA-transaminase, and NAD(+)-linked ICDH were reduced in 14 and 21-day-old pups. The enzyme activities of NADP(+)-linked ICDH activities remained unaffected in the fetus and developing pups brain. Maternal rehabilitation on iron sufficient diet for 1 week from day 14 to 21 of lactation period did not reverse these changes. The maternal iron deficiency during lactation period alone did not cause any alteration in all parameters assayed, however, there was a reduction in liver non-heme iron of pups on days 14 and 21.