OBJECTIVETo investigate the potential developmental toxicity of Radix Ophiopogonis decoction in SD rats.

METHODTimed-pregnant SD rats were given Radix Ophiopogonis decoction (26.9 g x kg(-1)) or vehicle (distilled water) by gavage on gestation days 6-17. Maternal clinical sign, abortions, premature deliveries, and body weight were monitored throughout gestation. At termination (gestation days 20) pregnant females were evaluated for clinical status and gestational outcome; live fetuses were examined for gender, external, visceral and skeletal malformation and variations.

RESULTNo deaths, premature deliveries or dose-related clinical signs were attributed to Radix Ophiopogonis decoction. Maternal body weight and body weight gain were not affected. There were no effects on fetus weight and viability, incidences of fetal malformation and variation.

CONCLUSIONThese results demonstrated that Radix Ophiopogonis decoction had no detectable adverse effects in either the treated F0 female rats or the fetuses.

Animals ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Embryonic Development ; drug effects ; Female ; Fetal Development ; drug effects ; Fetal Weight ; drug effects ; Humans ; Male ; Models, Animal ; Ophiopogon ; chemistry ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The study aims to investigate the embryo-fetus development toxicity of the novel PPAR-δ agonist HS060098 on SD rats. The pregnant rats that were randomly divided into the solvent control group (1% hydroxypropyl methyl cellulose water solution) and HS060098 suspension groups (10, 30 and 100 mg x kg(-1) xd(-1)) were orally administered with HS060098 suspension or vehicle during the gestation of 6 -15 days (GD6-15). At termination (GD20), female rats were sacrificed. The pregnant females were evaluated by corpora lutea count, implantation sites, existence and death of embryos. Fetal sex, weight, externals, variations and malformations of viscus and skeleton were observed. The results show that there were no significant abnormality in maternal general conditions and fetal appearance as well as viscera, but in the 100 mg x kg(-1) x d(-1) group, the maternal weight gain decreased greatly (P < 0.01) and the skeletal ossification delayed remarkably (P < 0.01); in the 30 mg x kg(-1) xd(-1) group, the fatal and litter number of incompletely ossified sternebrae II was higher than those of the control group (P < 0.05); the skeletal malformations occurred in all dose groups, which indicate that the novel PPAR-δ agonist HS060098 had maternal toxicity and adversely effected fetal skeletal development under the experimental conditions.
Animals ; Bone and Bones ; drug effects ; Embryonic Development ; drug effects ; Female ; Fetal Weight ; PPAR delta ; agonists ; Pregnancy ; Rats ; Toxicity Tests

In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats.
Animal ; Body Weight/drug effects ; Embryo/drug effects* ; Embryo Loss/prevention & control ; Embryo Loss/chemically induced ; Female ; Fetal Weight/drug effects ; Garlic* ; Methylmercury Compounds/toxicity* ; Methylmercury Compounds/pharmacokinetics ; Osteogenesis/drug effects ; Pregnancy ; Rats ; Rats, Inbred F344 ; Tissue Distribution

OBJECTIVETo investigate the effect of nonylphenol (NP) exposure on the genital development of fetal male rats in pregnant rats, and to measure the mRNA and protein expression of insulin-like factor3 (Insl-3) in the testicular tissue of fetal rats.

METHODSA total of 100 pregnant SD rats were equally assigned to blank control group and four NP treated groups. Each rat in the NP treated groups received intragastric administration of NP at doses of 5, 40, 100, or 200 mg/kg/d from day 14 to 19 of gestation, and the rats in the blank control group received intragastric administration of pure peanut oil. The pregnant rats were sacrificed on day 19 of gestation. The body weight and testicular weight of each fetal rat were measured, and the descent of testis was also observed. The mRNA and protein expression of Insl-3 in the testicular tissue of fetal rats was analyzed by reverse transcription-PCR and Western blot.

RESULTSCompared with the blank control group, the 40, 100, and 200 mg/kg NP treated groups showed significantly decreased body weight and weight coefficient of testis (P < 0.05 or P < 0.01), significantly decreased testicular descent (P < 0.05), and significantly decreased mRNA and protein expression of Insl-3 (P < 0.05 or P < 0.01).

CONCLUSIONExposure to nonylphenol can lead to testicular maldevelopment, incomplete testicular descent, and Insl-3 expression downregulation of fetal male rats in pregnant rats.

Animals ; Body Weight ; Female ; Fetal Development ; drug effects ; Insulin ; metabolism ; Male ; Maternal Exposure ; adverse effects ; Organ Size ; Phenols ; toxicity ; Pregnancy ; Proteins ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; embryology ; pathology

The effect of dexamethasone of the maturation of the fetal lungs of rats with streptozotocin-induced diabetes was studied morphologically and biochemically. By light and electron microscopy there was little difference in fetal pulmonary maturation between the untreated control group and the untreated diabetic group, but when both groups were treated with dexamethasone the fetuses showed accelerated pulmonary maturation, approximately one day earlier with an increase of air spaces per unit area and an earlier appearance of type II pneumocytes. The number of osmiophilic inclusion bodies per alveolus and per type II pneumocyte, and the lecithin/sphingomyelin ratio in amniotic fluid increased markedly and they were statistically significant in both groups injected with dexamethasone, but were decreased in the untreated diabetic group, though only the L/S ratio of the animals of the 19th day gestation was statistically significant. Phosphatidylglycerol was present in the amniotic fluid of the groups injected with dexamethasone one day earlier than the untreated control and the untreated diabetic groups. However, the intensity of phosphatidylglycerol tended to be lower in the untreated diabetic group. It is concluded that the prenatal administration of dexamethasone to the diabetic pregnant rats will accelerate fetal pulmonary maturation morphologically and promote the synthesis of surfactant biochemically.
Animal ; Blood Glucose/analysis ; Body Weight ; Comparative Study ; Dexamethasone/pharmacology* ; Diabetes Mellitus, Experimental* ; Female ; Fetal Organ Maturity/drug effects ; Fetus/cytology ; Lung/drug effects ; Lung/embryology* ; Lung/pathology ; Pregnancy ; Pregnancy in Diabetics* ; Rats ; Rats, Inbred Strains

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.
Body Height ; Body Mass Index ; Body Weight ; Child Development/drug effects* ; Cohort Studies ; Dietary Supplements ; Docosahexaenoic Acids/pharmacology* ; Female ; Humans ; Infant ; Infant, Newborn/physiology* ; Maternal-Fetal Exchange ; Parturition ; Pregnancy ; Pregnancy Outcome ; Prenatal Care ; Weight Gain

OBJECTIVETo study the reproductive toxicity of metadoxine.

METHODSMale and female rats were given metadoxine before pregnancy and early gestation, i.e. to feed metadoxine to male rats for 60 days before copulation and continue feeding during copulation, and feed metadoxine to female rats for 14 days before copulation.

RESULTSNo significant toxic effect was observed in the 400 mg/kg group. A few rats showed paralysis of hind leg in the 800 mg/kg group. The dosage of 1 600 mg/kg caused significant paralysis of hind legs, emaciation, and reduced weight gain. In the 1600 mg/kg group, the mating rate of male rats was significantly affected (P < 0.01). In the 800 and 1 600 mg/kg group, fertility of male rats was markedly reduced (P < 0.01). In the 800 mg/kg group, the effect on sperm counts of epididymis of male rats was markedly reduced (P < 0.05). In the 1 600 mg/kg group, testicle weight and body weight ratio and sperm counts of epididymis rate were significantly (P < 0.001) reduced. In the 1 600 mg/kg group, the fertility rate of female rats was remarkably (P < 0.001) reduced. In the 800 mg/kg group, the weight gain of pregnant rats was significantly reduced (P < 0.001). In both the 800 and 1 600 mg/kg groups, the gestation rate was greatly reduced (P < 0.001). In the 800 mg/kg group, mortality rate before nidation (P < 0.001) and average live fetus number were significantly reduced (P < 0.05). In the 400 mg/kg group, the fetal weight was significantly reduced (P < 0.001). In the 800 mg/kg group, body length, tail length, body weight and sternum development of fetal rats were significantly affected (P < 0.001).

CONCLUSIONUnder the presented experimental conditions, metadoxine has no teratogenic effects on SD rats and the no effect dose is 400 mg/kg. And the no effect dose for the developmental toxicity is less than 400 mg/kg.

Animals ; Dose-Response Relationship, Drug ; Drug Combinations ; Female ; Fertility ; drug effects ; Fetal Weight ; Male ; Organ Size ; Pregnancy ; Pyridoxine ; toxicity ; Pyrrolidonecarboxylic Acid ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Testis ; anatomy & histology

OBJECTIVETo study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR.

METHODSA total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac).

RESULTSThe FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (P<0.05). The FGR group had significantly higher mRNA expression of RhoA and ROCK2 than the control group. The taurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (P<0.05). The FGR group had significantly lower mRNA expression of Rac than the control group. The taurine group had significantly higher mRNA expression of Rac than the FGR and control groups (P<0.05). The FGR group had significantly higher protein expression of RhoA and ROCK2 than the control group. The taurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (P<0.05).

CONCLUSIONSAntepartum taurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

Animals ; Animals, Newborn ; Body Weight ; drug effects ; Brain ; drug effects ; Cell Proliferation ; drug effects ; Fatty Acid-Binding Protein 7 ; analysis ; Female ; Fetal Growth Retardation ; drug therapy ; Male ; Neural Stem Cells ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Taurine ; pharmacology ; rho-Associated Kinases ; analysis ; genetics ; rhoA GTP-Binding Protein ; analysis ; genetics

OBJECTIVETo investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF-alpha and IR; and to find out a reasonable early nutritional intervention measure for the prevention of IR, through giving different diets to offspring.

METHODSAn IUGR model was built by maternal nutrition restriction. 80 newborn IUGR female pups were randomly divided into 4 groups, the mother rats were given the following diet respectively for 3 weeks after delivery, pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high-caloric diet group (group A), (3) IUGR high-protein and high-caloric diet group (group B) and (4) IUGR high-protein isocaloric diet group (group C). Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N). All pups were weaned at the 4th week of age and fed with normal diet till the end of the experiment. At the 12th week (adulthood) and 48th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF-alpha of adipose tissue and body weight were measured. Body mass index (BMI), ISI (insulin sensitive index), IRI (insulin resistant index) and HBCI (beta cell insulin excretion index) and their correlation to TNF-alpha were calculated.

RESULTSAt 12th week and 48th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups. TNF-alpha was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI. Group A and B was fatter and developed more severe IR. There were no significant differences in ISI, IRI, HBCI and TNF-alpha between group C and group C/N.

CONCLUSIONSIUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12th week. TNF-alpha was closely related to the occurrence of IR in IUGR pups. IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality. The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood.

Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin Resistance ; physiology ; Malnutrition ; physiopathology ; Pregnancy ; Pregnancy Complications ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet.

METHODSIUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group (S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week.

RESULTS(1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length.

CONCLUSIONSThe serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the absorption of nutrition.

Animals ; Animals, Newborn ; growth & development ; Body Weight ; drug effects ; Dietary Proteins ; pharmacology ; Female ; Fetal Growth Retardation ; blood ; etiology ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Intestines ; growth & development ; pathology ; Nutritional Physiological Phenomena ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley