Use of diet containing yeast protein (Saccharomyces cerevisiae): effects upon pregnancy, lactation and development in rats

The nutritive value of manioc flour (Manihot esculenta) enriched with yeast protein (Saccharomyces cerevisiae) added to a food mixture most frequently consumed by low-income populations was assessed in female Wistar rats (n = 30; 100-120 days old). Animals were divided into three groups, mated and had free access to diets and water. Diets were as follows: beans, rice, yeast-enriched manioc flour (BRYMF17); beans, rice, manioc flour (BRMF13); casein (17% protein) (CAS17). Body weight gains and food consumption were recorded during pregnancy and lactation. At the parturition, the number of pups per litter was recorded and offspring were uniformly distributed (7 pups per litter). Weight gains were determined until weaning (21 days). At weaning two youngs were selected from each litter and individually housed. Weight gains, food consumption and the length of the tail were measured until rats were 70 days old. Rats had their liver and brain removed for protein determination and wet and relative weights. Liver samples were histologically examined. Blood hemoglobin, hematocrit and proteins, as well as the Food Efficiency Ratio (FER), were determined. ANOVA and Tukey's test were used. The experimental diet had not significant effect on pregnant and lactating dams. Values for the investigated parameters were higher in experimental youngs than in their controls and lower than in the standard group. This yeast protein-enriched manioc flour proved to be valid in terms of dietary supplementation.     

Additive effects of protein malnutrition and cortisol on plasma proteins and immunoglobulins of pregnant rats, and their offsprings

This research work was carried out to study the effects of two immunosuppressive mechanisms: protein malnutrition and cortisol treatment on the feto-maternal unit. Therefore, plasma Ig G and Ig M levels were tested in pregnant rats submitted to a low protein diet (4%) and cortisol treatment (0.5 mg/100 g b.w.) during pregnancy and in their offspring. Nutritional status was evaluated by measuring ponderal parameters and plasma protein levels in rat dams and their neonates. Thus, a fall in ponderal parameters and in plasma protein levels was observed, both in rat dams suffering protein malnutrition as well as in their newborns. Cortisol treatment produced a decrease in the ponderal parameters of the control group, and an increase in plasma protein levels of the malnourished one, both in rat dams and in their neonates. Apparently, protein malnutrition might lead to a low functionality of B lymphocytes, caused by a decrease in Ig G and Ig M rates of malnourished rat dams. Ig M levels, however, increased in neonates as a consequence of possible concomitant infections. Cortisol treatment promoted humoral immune deficiency, since Ig G and Ig M levels decreased both in the control and in the malnourished pregnant rat groups. Nevertheless, cortisol administration seemed to increase susceptibility to infection in the newborns, especially in those born from malnourished rat dams.     

Influence of dietary protein levels on the electrophoretic pattern and plasma IgG and IgM levels in pregnant rats and their offspring

In view of the influence that nutritional and physiological status exert on the immunological capacity of the subject, a study was carried out for the purpose of studying the changes induced by three protein levels in the diet: (4%, 10% (control), and 20%) on total plasma proteins (TPP) and their fractions, as well as Ig G and Ig M levels in non-pregnant (NP) and pregnant (P) rats and their offspring. Effect of the diet on adult rats--In non-pregnant rats submitted to the high protein diet, Ig G levels increased while TPP decreased in P rats fed on 4% and 20% protein diets. The higher the protein level in the diet, the higher were the TPP values. Effect of pregnancy--Ig G and Ig M levels suffered an increase in rats fed the 4% and 10% protein diets, while a decrease was observed in rats submitted to the 20% protein level diet. The TPP rate diminished in rats fed on the low protein diets, and increased when the highest protein diet was administered. Effect of the diet on offspring--Ig M levels were only detected in neonates from rats fed with the low and high protein diets. Moreover, the TPP rate increased as a direct function of the dietary protein intake.     

Nutritional utilization of a low protein diet in alloxan diabetic rats

Dietary control is known to influence diabetic processes. Therefore, the purpose of this work was to determine possible effects brought about by two different dietary protein levels on the nutritional diet utilization in alloxan-diabetic rats. Rats were divided in two groups: 1) One fed on 12% and 2) one a 4% protein diet. Each group was then divided into two subgroups: A) non diabetic and B) diabetic. Weight parameters, food intake, food efficiency (FE), digestive efficiency (DE), metabolic utilization (MU), retained N/ingested N ratio as well as initial and final glycemia were evaluated at the beginning and at the end of the experiment. A decrease in body weight, FE, DE and MU was observed in the control rats of group 2A, in comparison with the group 1A. Experimental diabetes led to increased FE in 1B group in relation to those of group 1A. Also decreased body weight and FE as well as increased food intake and DE were found in the control animals of 2B group. Glycemia increased in diabetic rats as compared with non-diabetic rats, in both groups, 1 and 2. The data suggest that under the experimental conditions cited, both the nutritional utilization of the diet and the diabetogenic status might be modulated by the dietary protein ingested level.     

Effects of cholesterol feeding to maternal rats on metabolism of cholesterol and bile acids in the dams and their offspring

The influence of feeding cholesterol to rats during pregnancy and postpartum (from the 11th day of gestation to the third day after delivery) on the serum and hepatic cholesterol levels and on the bile acid composition in the pool and in the liver in relationship to the dams and their pups was examined. The hepatic content of cholesterol in both dam and offspring increased during cholesterol feeding without any changes in serum cholesterol level. In the dams, mainly the esterified cholesterol was increased; in the pups, mainly the free cholesterol was increased. Cholesterol feeding led to a pronounced increase in the pool of β-muricholic acid and a relative decrease in the lithocholic acid concentration in pregnant rats. In fetal rats, the chenodeoxycholic acid pool was increased by cholesterol intake. The lithocholic acid pool was larger in the postpartum rats fed cholesterol than in the controls, while the concentration of α- and β-muricholic acids was decreased. The neonates of cholesterol-fed dams had a larger pool of chenodeoxycholic acid but a smaller pool of β-muricholic acid. These results suggest that the metabolism of cholesterol and of bile acids in dams and their offspring respond differently to cholesterol intake.     

Influence of rabbit milk upon cholesterolaemic response of offspring of rabbits

The milk lipids from the dams of two strains of rabbits differing in their cholesterolaemic response, one hyperresponsive and one hyporesponsive to dietary cholesterol, were analyzed. The hyperresponsive dams had significantly higher (P<0.05) cholesterol and phospholipid concentrations than the hyporesponsive dams but similar triglyceride concentrations. Cross fostering experiments with hyporesponsive and hyperresponsive offspring were carried out. Offspring from hyporesponsive parents suckled on hyper-responsive dams resembled hyperresponsive offspring in their cholesterolaemic response. However, offspring from hyper-responsive parents responded as hyper-responsive whether they were raised on their natural dams or on foster hyporesponsive dams. We conclude that the trait for hyperresponder characteristics is un-influenced by rabbit milk, while the trait for hyporesponder characteristics is dependent upon the cholesterol and phospholipid concentrations in milk.     

Maternal Dietary Fat Affects Milk Fatty Acid Profile and Impacts on Weight Gain and Thermogenic Capacity of Suckling Rats

We aimed to assess the effects of maternal supplementation with the main fat sources used in the human Western diet (olive oil, butter, margarine) on milk FA composition and on plasma FA profile of offspring, and to determine whether it may influence body-weight-gain (BWG) and adiposity of offspring during the suckling period. Wistar rats were supplemented with the different fat sources from day 14 of gestation and throughout lactation. Olive oil-supplemented dams showed the highest proportion of oleic-acid in milk, with no changes in plasma. Their offspring also showed the highest proportion of this FA in plasma, lower BWG during the suckling period, and higher levels of UCP1 in brown adipose tissue (BAT) at weaning. Margarine-supplemented dams showed the highest percentage of PUFA in milk, and a similar tendency was found in plasma of their offspring. Butter-supplemented dams displayed higher proportion of saturated FA (SFA) in milk compared to other fat-supplemented dams, but lower than controls. Control offspring also showed higher proportion of SFA in plasma and greater BWG during the suckling period than fat-supplemented groups. Significant correlations were found between the relative content of some milk FA and BWG of offspring, in particular, oleic-acid levels correlated negatively with BWG and positively with UCP1 levels. These results show that maternal dietary source of fat affects milk FA composition and circulating FA profile, as could be expected, but also BWG and thermogenic capacity of offspring during the suckling period. An effect of oleic-acid stimulating BAT thermogenic capacity of suckling pups is proposed.     

Lipid composition of the placenta of rats with protein restriction and deficiency of essential fatty acids

The influence of diet restriction and EFA deficiency during pregnancy in the rat on the lipid and phospholipids composition of the placenta was investigated. Female virgin albino Wistar rats weighing 130 +/- 4 g, were assigned to three equivalent groups. Prior mating and during pregnancy each group of rats received the following regimen: Animals in the Control Group (C) were fed a 25% casein diet in ad libitum quantities; the dietary Restricted Group (D) received the same control diet in amounts calculated to approximate 50% (g/100 g rat) of the intake of group C; the Deficient and Restricted Group (DD) rats were fed a restricted amount of EFA deficient diet. On the 21st day of gestation pregnant animals were sacrificed. The foetuses and placentae obtained by caesarium section were isolated and weighed. A 50% food restriction before and during pregnancy resulted in a significant decrease in phospholipid contents (p less than 0.05); severe EFA deficiency superimposed to 50% food restriction, moreover induced significant changes in the fatty acid pattern of phospholipids, decreasing n3 and n6 fatty acids and increasing eicosatrienoic acid. There was an accumulation of triglycerides in the placenta of rats fed on the EFA deficient diet. In the two restricted groups fetal weight was reduced, but although in the DD group, placental weight was not affected, litter size was dramatically reduced.     

Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model

Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.     

Maternal High Folic Acid Supplement Promotes Glucose Intolerance and Insulin Resistance in Male Mouse Offspring Fed a High-Fat Diet

Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p = 0.009), glucose intolerance (p < 0.001) and insulin resistance (p < 0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring.     

Exposure to Atrazine during Gestation and Lactation Periods: Toxicity Effects on Dopaminergic Neurons in Offspring by Downregulation of Nurr1 and VMAT2

High atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR) contents in the environment threaten the health conditions of organisms. We examined the effects of ATR exposure on Sprague-Dawley rats during gestation and on the dopaminergic neurons of offspring during lactation. Pregnant dams were orally treated with 0 mg/kg/day to 50 mg/kg/day of ATR from gestational day 5 to postnatal day 22. Afterward, neither offspring nor dams received ATR. Dopamine (DA) content was examined in striatum samples by HPLC-FL; the mRNA expressions of tyrosine hydroxylase (TH), orphan nuclear hormone (Nurr1), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) in the ventral midbrain samples were examined by fluorescence PCR when the offspring reached one year of age. After the pregnant rats were exposed to ATR, the DA concentrations and mRNA levels of Nurr1 were decreased in their offspring. Decreased Nurr1 levels were also accompanied by changes in the mRNA levels of VMAT2, which controls the transport and reuptake of DA.     

Oleoyl-Estrone Treatment to Late Pregnant and Mid-Lactating Rats Affects the Expression of Lipid Metabolism Genes

The purpose of this study was to determine whether OE treatment affects the expression of genes related to lipid metabolism under two physiological conditions: late pregnancy and mid-lactation, both characterized by lipid mobilization. Samples of periovarian and retroperitoneal adipose tissue from 21-day pregnant or 15-day lactating dams were used. The expression of LPL, FATP1, FABP4, HSL, ACC1, FAS, PEPCK, GLUT4, PDK4, SREBP1c, adiponutrin and leptin, were compared with their expression in virgin rats. In pregnant rats, FABP4, HSL, PEPCK and PDK4 were over expressed in the periovarian site compared to virgin rats, whereas adiponutrin, FAS, GLUT4 and SREBP1c were underexpressed; the retroperitoneal fat depot showed a similar pattern but ACC1 and leptin were also underexpressed. OE treatment caused a generalized decrease in gene expression in both adipose depots. In lactating dams, the gene expression profile at the periovarian depot was similar to that observed in pregnant rats. OE treatment mimicked the trend observed in pregnant rats, although the intensity of the gene expression changes was lower. After OE treatment, the retroperitoneal adipose depot showed a completely different pattern since the values were close to those of virgin rats. These results corroborate that OE effects in adipose tissue, lowering lipids and depressing their metabolism, already described under other physiological situations, can be also found in late pregnancy and lactation.     

Maternal High-Fat Diet Modulates Hepatic Glucose,Lipid Homeostasis and Gene Expression in the PPAR Pathway in the Early Life of Offspring

Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway.     

Trabecular Bone Parameters,TIMP-2, MMP-8, MMP-13, VEGF Expression and Immunolocalization in Bone and Cartilage in Newborn Offspring Prenatally Exposed to Fumonisins

Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner.     

Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.     

A Maternal High Fat Diet Has Long‐Lasting Effects on Skeletal Muscle Lipid and PLIN Protein Content in Rat Offspring at Young Adulthood

A maternal high fat diet (HFD) can have adverse effects on skeletal muscle development. Skeletal muscle PLIN proteins (PLIN2, 3 and 5) are thought to play critical roles in lipid metabolism, however effects of HFD on PLIN and lipases (HSL, ATGL, CGI‐58) in mothers as well as their offspring have yet to be investigated. The primary objective of this study was to determine whether maternal HFD would influence skeletal muscle lipase and PLIN protein content in offspring at weaning (19d) and young adulthood (3mo). Female rats (28d old, n = 9/group) were fed control (CON, AIN93G, 7 % soybean oil) or HFD (AIN93G, 20 % lard) for 10 weeks prior to mating and throughout pregnancy and lactation. All offspring were weaned to CON [n = 18/group, 1 female and 1 male pup per litter were studied at weaning (19d) and 3mo of age]. There was no effect of sex for the main outcomes measured in plantaris, therefore male and female data was combined. Maternal HFD resulted in higher triacylglycerol content in pups at 3mo (p < 0.05), as well as in the dams (p = 0.015). Maternal HFD resulted in higher PLIN5 content in pups at weaning and 3mo (p = 0.05). PLIN2 and PLIN5 content decreased at 3mo versus weaning (p < 0.001). HFD dams had a higher PLIN3 content (p = 0.016). Diet had no effect on ATGL, CGI‐58, or HSL content. In conclusion, exposure to a maternal HFD resulted in higher skeletal muscle lipid and PLIN5 content in plantaris of offspring through to young adulthood.     

Dietary effect of gamma-linolenic acid on the lipid profile of rat fed erucic acid rich oil

This study evaluated the effects of dietary supplementation of gamma-Linolenic acid (18:3n-6, GLA) on the lipid profile of serum and other tissues of rats fed erucic acid (C22:1) rich oil like mustard oil. The rats were fed diet containing 20% mustard oil as erucic acid rich oil and 20% groundnut oil as dietary fat. These groups were kept as reference groups. Another group fed diet containing 20% fat to which evening primrose oil as a source of GLA was blended with mustard oil and groundnut oil at 5% level. The feeding experiment was done for 4 weeks. In another set mustard oil fed group was kept as control while the experimental group was fed evening primrose oil as a source of GLA blended with mustard oil at 2.5% level. The feeding experiment was carried out for 12 weeks. The other dietary components remained same for all the groups. After the scheduled feeding period, it was found that there was no significant change in weight gain, food intake and food efficiency ratio. It was found that dietary GLA resulted in significant decrease in serum triglyceride (TG) and very low density lipoprotein (VLDL) cholesterol and significant increase in high density lipoprotein (HDL) cholesterol in serum in the experimental group. In liver total cholesterol (TC) is significantly higher and in heart and liver TG is significantly lower in GLA fed group.     

Cellular growth of uterus, placenta and fetus during chronic maternal caloric restriction in rats

Wistar strain female rats were maintained with restricted amounts of 25% casein diet before and during pregnancy. Uteri, placentas and fetuses were removed from the rats beginning the 14th day of conception and continuing it up to the 20th day. Tissues were analyzed in regard to weight, nucleic acids and protein content. A 25% food restriction decreased dramatically the uterine, placental and fetal size as well as DNA content. RNA and protein content were also found diminished, but it must be emphasized that these findings were less important than the DNA content reduction observed. This is the reason why RNA/DNA and protein/DNA ratios were markedly elevated in regard to control values. Cellular changes observed in the reproductive organs and their relationships with fetal growth failure, induced by maternal dietary modification, are discussed.     

A regional basic diet from northeast Brazil as a dietary model of experimental malnutrition

The nutritional potentiality of the "Regional Basic Diet" (RBD) was assessed in albino rats. The diet, which was prepared according to data from food consumption surveys and was similar--in terms of quality and quantity--to those consumed by human populations in Northeast Brazil, was compared to a balanced diet (22% casein). The centesimal composition, aminogram, minerals content, NDpCal% and GCal%/PCal% ratio were determined. Vitamin contents were calculated from data in the literature. The RBD was shown to be imbalanced and poor in certain nutrients, mainly protein (7.8%). The growth curve of the RBD group was severely impaired; the naturally occurring sex-related differences in body weight were not detected. For fetuses and suckling pups, the weights of the liver and diaphragm paralleled body weight; brain weights were about 20% lower than those of controls, and its ratio was higher. RBD pregnant females presented, despite their higher food and energy intakes, lower weight gain as compared to the controls. During lactation food and energy intakes of RBD dams were lower than those of controls. The mortality rate among RBD pups was 24%. Our data indicate that RBD produces in the rat a type of malnutrition similar to that prevalent among children from Northeast Brazil, namely an association to nutritional dwarfism with some clinical signs of marasmus. RBD is considered to be a useful experimental model for studies on human malnutrition in countries where basic food patterns are similar to those in RBD-consuming regions.     

注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白对大鼠生育力及早期胚胎发育的毒性作用

目的观察注射用重组人B淋巴细胞刺激因子受体-抗体融合蛋白(RCT-18)对大鼠生育力及早期胚胎发育的毒性作用。方法将SD大鼠随机分为4组,分别经皮下注射RCT-18 129、37、11 mg/(kg.d)和0.9%NaCl注射液,每2 d给药1次。雄鼠连续给药5周、雌鼠连续给药2周后,按雌雄1∶1的比例合笼交配,合笼期为2周,计算交配率。雄鼠继续给药至交配成功,雌鼠继续给药至妊娠第6天。实验过程中观察动物的一般反应、体重及摄食量变化。确定雌鼠受精后处死雄鼠,解剖检查睾丸和附睾等生殖器官。于妊娠第15天解剖孕鼠,综合评价妊娠及胚胎形成和早期发育等情况。结果 RCT-18高、中、低剂量组雌性和雄性大鼠均未出现明显的母体毒性反应。各组大鼠各脏器均未见肉眼可见的异常。各剂量RCT-18对大鼠的交配率、妊娠率、生殖系统脏器重量和系数以及早期胚胎发育均无明显影响。结论RCT-18对SD大鼠的生育力及早期胚胎发育无明显毒性作用。