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Objective To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR). Study design Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth. Results One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine β-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection. Conclusions Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection.

Systemic lupus erythematosus (SLE) involves multiple organ systems and primarily affects women during their reproductive years. Pregnancy in a woman with SLE may lead to higher rates of disease flares. Little is known regarding which medications are safe to maintain remission and/or treat flares throughout such pregnancies. Here we retrospectively analyzed the efficacy of tacrolimus (TAC) in the pregnancy outcomes of SLE patients. We studied the 54 deliveries of 40 SLE patients over an eight-year period from 2008 to 2016. We used analyses of covariance with adjustments for the propensity score and inverse probability of treatment weights to compare the patient backgrounds between the TAC users and non-TAC users. TAC was administered to the patient in 15 of the 54 (27.8%) pregnancies, and these patients had a significantly higher dose of prednisolone, hypocomplementemia, lower estimated glomerular filtration rate, past history of lupus nephritis, and complication with antiphospholipid syndrome. In the adjusted background of the TAC deliveries, the risks of decreased fetal body weight, low birth weight infant, non-reassuring fetal status (NRFS), and preterm birth were not increased compared to the non-TAC deliveries. Thrombocytopenia and hypertension during the pregnancy were extracted as independent predictive risk factors for decreased fetal body weight and NRFS, respectively. We had anticipated that the maternal and fetal outcomes in the TAC-use deliveries would be poor before the analysis; however, the TAC-use group showed no significant difference in risks contributing to outcomes compared to the non-TAC group, suggesting that adjunct TAC treatment corrected various risk factors during the lupus pregnancies.

Low birth weight may negatively affect energy storage and nutrient metabolism, and impair fetal growth and development. We analyzed effects of body weight (BW) and gestational period on nutrient composition in fetal Huanjiang mini-pigs. Fetuses with the lowest BW (LBW), middle BW (MBW), and highest BW (HBW) were collected at days 45, 75, and 110 of gestation. Crude protein (CP), crude fat, amino acid (AA), and fatty acid (FA) concentrations were determined. The BW gain, carcass weight, fat percentage, and uterus weight of sows increased as gestation progressed, as did litter weight, average individual fetal weight, fetal body weight, and dry matter (DM). The concentrations of Ala, Arg, crude fat, Gly, Pro, Tyr, C14:0, C16:0, C16:1, C18:1n9c, C18:2n6c, C18:3n3, C18:3n6, C20:0, C20:3n6, saturated FA (SFA), and monounsaturated FA (MUFA) increased significantly as gestation progressed. The percentage of skeleton, and the ratio of the liver, lung, and stomach to BW decreased as gestation progressed. There were also significant reductions in the concentrations of CP, Asp, Glu, His, Ile, Leu, Lys, Phe, Ser, Thr, essential AA (EAA), acidic AA, C17:0, C20:4n6, C22:6n3, unsaturated FA (UFA), polyunsaturated FA (PUFA), n-3PUFA, n-6PUFA as gestation progressed, and reductions in EAA/total AA (TAA), PUFA/SFA, and n-3/n-6 PUFA. The LBW fetuses exhibited the lowest BW and crude fat, C14:0, C16:1, C17:0, C18:2n6c, and MUFA concentrations at days 75 and 110 of gestation. They also exhibited lower Tyr concentration at day 45 of gestation and lower Glu concentration at day 75 of gestation than HBW fetuses. These findings suggest that LBW fetuses exhibit lower amounts of crude fat and several FAs during mid-gestation and late-gestation, which may in turn affect adaptability, growth, and development.

Dietary supplement and natural product use is increasing within the United States, resulting in growing concern for exposure in vulnerable populations, including young adults and women of child-bearing potential. Vinpocetine is a semi-synthetic derivative of the Vinca minor extract, vincamine. Human exposure to vinpocetine occurs through its use as a dietary supplement for its purported nootropic and neuroprotective effects. To investigate the effects of vinpocetine on embryo-fetal development, groups of 25 pregnant Sprague-Dawley rats and 8 pregnant New Zealand White rabbits were orally administered 0, 5, 20, or 60 mg vinpocetine/kg and 0, 25, 75, 150, or 300 mg/kg daily from gestational day (GD) 6-20 and GD 7-28, respectively. Pregnant rats dosed with vinpocetine demonstrated dose-dependent increases in post-implantation loss, higher frequency of early and total resorptions, lower fetal body weights, and fewer live fetuses following administration of 60 mg/kg, in the absence of maternal toxicity. Additionally, the rat fetuses displayed dose-dependent increases in the incidences of ventricular septum defects and full supernumerary thoracolumbar ribs. Similarly, albeit at higher doses than the rats, pregnant rabbits administered vinpocetine displayed an increase in post-implantation loss and fewer live fetuses (300 mg/kg), in addition to significantly lower fetal body weights (≥ 75 mg/kg). In conclusion, vinpocetine exposure resulted in similar effects on embryo-fetal development in the rat and rabbit. The species differences in sensitivity and magnitude of response is likely attributable to a species difference in metabolism. Taken together, these data suggest a potential hazard for pregnant women who may be taking vinpocetine.

The present study was designed to explore if maternal subtotal (5/6) nephrectomy affects the development of fetal rat kidneys using morphometric methods and examining whether there are any apoptotic changes in the fetal kidney. To generate 5/6 nephrectomized model rats, animals underwent 2/3 left nephrectomy on gestation day (GD) 5 and total right nephrectomy on GD 12. The fetal kidneys were examined on GDs 16 and 22. A significant decrease in fetal body weight resulting from maternal 5/6 nephrectomy was observed on GD 16, and a significant decrease in fetal renal weight and fetal body weight caused by maternal nephrectomy was observed on GD 22. Maternal 5/6 nephrectomy induced a significant increase in glomerular number, proximal tubular length, and total proximal tubular volume of fetuses on GD 22. Maternal 5/6 nephrectomy resulted in an increase in the number of apoptotic cells in the metanephric mesenchyme of the kidney on GD 16, and in the collecting tubules on GD 22. These findings suggest that maternal 5/6 nephrectomy stimulates the development of the fetal kidney while suppressing fetal growth.

Aim: this study aimed to investigate the protective effect of extra-virgin olive oil (EVOO) against teratogenicity of the fungicide mancozeb. Methods: after pregnancy confirmation, 32 pregnant rats were divided into 4-groups (n=8). The 1st group orally administered tap water (-ve control), the 2nd group (+ve control) was administered EVOO (0.5ml/dam) from the1st to 20th day of pregnancy. The 3rd and the 4th groups were administered 200 mg/kg mancozeb during the period of organogenesis, from the 6th to 15th day of pregnancy. The 4th group received the mentioned dose of EVOO prior to the pesticide administration. Cesarean section was performed on day 20 of pregnancy and the maternal and fetal parameters were recorded. Results: mancozeb induced maternal toxicity manifested as lower body weight gain of dams, increased number of late resorption sites/litter in comparison with the control group and mancozeb group pretreated with EVOO. Mancozeb evoked a decrease in fetal body weight, altered sex ratio (M/F) as well as increased incidence of fetal external, visceral and skeletal abnormalities. Treatment with virgin oil reduced the congenital malformations. Conclusively, the present study elucidates the protective role of EVOO as a result of antioxidant activity which scavenges the reactive oxygen species which induced cytotoxicity and increased prenatal mortalities.

Background: Pregnancy and lactation in adolescents with low calcium intake may impair fetal growth and infant bone mass. Objective: We investigated the effects of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers consuming low calcium diets (;600mg/d) on fetal biometry and infant bone mass, and the relation between infant and maternal bone mass during early lactation. Methods: Infants of mothers who received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition were studied. Fetal biometric measurements at 23 and 36 wk of gestation were obtained from medical records. Infant anthropometric and total body bone measurements [bone mineral content (BMC), bone area (BA), and bone mineral density (BMD)] at 5 wk postpartum were assessed by dual-energy X-ray absorptiometry. Maternal BMD z scores for total body, lumbar spine, total hip, and femoral neck at 5 wk postpartum were obtained. Group comparisons were adjusted for significant covariates. Results: Maternal mean serum 25-hydroxyvitamin D was 59 nmol/L at baseline in both groups. No differences in fetal measurements at 36 wk of gestation were observed between the groups, except for body weight and its increment from 23 to 36 wk, which were higher in the supplemented group (6.8%, P= 0.014 and 10.5%, P= 0.07, respectively). Infant BMC (61.1 6 21.7 g), BA (167 6 79 cm 2 ), and BMD (0.385 6 0.069 g/cm 2 ) did not significantly differ between the groups. In the placebo group, infant BMC and BA were negatively correlated with maternal BMD z scores for total body (r =20.40 and r =20.47; P< 0.05) and hip (r = 20.41 and r = 20.46; P < 0.05). In contrast, no correlations were observed in the supplemented group. Conclusions: Calcium and vitamin D supplementation of the adolescents studied resulted in higher fetal body weight at 36 wk of gestation and had no effect on infant bone mass at 5 wk postpartum. Because correlations between maternal and infant bone mass were evident only in the placebo group, infant bone mass appeared to be more dependent on maternal skeletal mass when calcium intake was low. This trial was registered at clinicaltrials.gov as NCT01732328. JN utrdoi: 10.3945/jn.114.208140.

Background: Carbamazepine "CBZ" (Tegretol) is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia. It has been assigned to pregnancy category D by the U.S Food and Drug Administration (FDA). CBZ can cause fetal harm when administered to pregnant women. Epidemiological data suggested that there may be an association between the use of CBZ during pregnancy and congenital malformations, specifically spina bifida and developmental disorders. The possible malformation-specific risks with CBZ use during pregnancy need to be considered, so the present work was conducted to evaluate the genotoxicity of two doses of CBZ (3.6 mg and 10.8 mg/ 100g body weight/ day) in pregnant female rats and their fetuses. Chromosomal aberration in bone marrow cells and histopathological examination of liver and kidney of pregnant rats were also determined. Materials and Methods: Fourty five pregnant Sprague Dawley rats were randomly divided into the groups. The first was administered oral doses of distilled water and served as control. The other two groups were administered oral doses of CBZ suspended in distilled water equivalent to 3.6 mg and 10.8 mg/100g body weight/day respectively for 15 day from the 6th day to the 20th day of gestation. Females were sacrificed on the 20th day of gestation. Results: Administration of CBZ 3.6 mg and 10.8 mg /100g body weight to pregnant rats from the 6th till the 20thday of gestation. Decreased fetal body weight, crown-rump length, increased resorbed and dead fetuses were observed compared to the control ones. Moreover, CBZ-high dose group(10.8mg/100g) causedmalformations that could be described as severe growth retardation. At the same time, bone marrow metaphases of CBZ-treated pregnant rats revealed structural chromosomal aberrations. Whereas, histopathological examination of liver and kidney of pregnant rats treated with both doses of CBZshowed cellular alterations.Conclusion:It has been found that usage of antiepileptic CBZ during gestational period may create risk, associated with maternal toxicity, hepato- and nephrotoxicity and chromosomal aberrations in pregnant rats, with intrauterine growth retardation which was manifested by low body weight, length reduction and malformations. These alterations were dose dependent. The benefits of taking CBZ must be weighed against the potential risks to boththe developing fetus and the mother.

Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

Aditoprim, a new bacteriostatic agent that belongs to diaminopyrimidines, has a broad antimicrobial spectrum, good antibacterial activity and excellent pharmacokinetics. To evaluate the reproductive toxicity and teratogenic potential of aditoprim, different concentrations of aditoprim were administered to Wistar rats by feeding diets containing 0, 20, 100 and 1000 mg kg(-1) , respectively. Each group consisting of 18 males and 25 females (F0 ) was treated with different concentrations of aditoprim through a 13-week period before mating and during mating, gestation, parturition and lactation. At weaning, 20 males and 25 females of the F1 generation weanlings per group were selected randomly as parents for the F2 generation. Selected F1 weanlings were exposed to the same diet and treatment as their parents. At 1000 mg kg(-1) dose group, body weights in F0 and F1 rats, fetal body weight on day 21 (0, 4 and 21) after birth and number of viable fetuses in the F0 and F1 generation significantly decreased. Teratogenicity study was performed in combination with the F1 generation of a two-generation reproduction study. F1 parents of the reproduction study were mated after weaning of the F2a pups. Pregnant female rats were subjected to cesarean section on gestational day 20 for teratogenic examination. At 1000 mg kg(-1) group, body weights, fetal body lengths, tail lengths, litter weights and number of viable fetuses were significantly decreased. No obvious external, skeletal or visceral malformations in fetuses were noted in any groups in the teratogenic test. The no-observed-adverse-effect level for reproduction/development toxicity of aditoprim was 100 mg kg(-1) diet (about 7.89-9.25 mg kg(-1) body weight day(-1) ).

Perfluorooctane sulfuric acid (PFOS) is a persistent organic pollutant, causes fetal growth retardation but the mechanism is still unclear. This study focused on PFOS-induced toxicity such as placental trophoblast cell histopathological changes, endocrine function (i.e., prolactin (PRL)-family hormone production) and subsequent fetal growth retardation in mice. Maternal body weight gain, placental and fetal weights were significantly decreased in proportion to PFOS dosage. Placental efficiency (fetal weight/placental weight) was significantly reduced dose-dependently. Necrotic changes were observed in PFOS-treated placental tissues, and the area of injury increased dose-dependently. Finally, mRNA levels and maternal serum concentrations of the PRL-family hormones (mPL-II, mPLP-Cα, mPLP-K) were significantly reduced dose-dependently. In addition, the changing pattern between PRL-family hormone concentrations and fetal body weight was positively correlated. These results suggest that gestational PFOS treatment induces placental histopathological changes and disruption of endocrine function, finally may lead to fetal growth retardation in mice.

In medical science, fetus growth is possible to be monitored from the USG results by means of an ultrasonography machine, such as to determine the fetus weight. Through the Shepard calculation method, the fetus weight can be calculated with the help of two parameters: Abdomen Circumference (AC) and Biparietal Diameter (BPD). The problem in the accuracy of weight measurement has become a challenge among paramedics to observe the health and growth of the fetus. This study aims to determine the accuracy level of fetal weight measurement using Fuzzy C Means (FCM) and Iterative Random Hough Transform (IRHT) method purposely to obtain parietal diameter (BPD) and stomach diameter (AC). The result of the measurement system has been compared with the output from the ultrasonography machine to determine the reliability of the application of the combination of those two methods. From the results of the test on the accuracy of measurement of the diameter and fetal body weight, it was found that the detection of BPD had an error rate of 24.3% of the measurement of USG machine. For the percentage of the error level of abdominal measurement (AC) it reached 10.64% and in the prediction of fetal weight from the system proposed, it had an accuracy of 62.32% of ultrasonography machine measurements.

Objectives: The aim of the study is to determine the impact of the experimental diabetes and the chronic hypoxia on pregnancy development and rat fetal body weight. Material and methods: The experiment was performed on female Wistar rats. Animals were divided into the experimen­tal groups. I — Controls, II — Untreated diabetes, III — Insulin-treated diabetes, IV — No diabetes with chronic hypoxia, V — Untreated diabetes and chronic hypoxia, VI — Insulin- treated diabetes and chronic hypoxia. Diabetes was induced in groups II, III, V and VI with intraperitoneal injection of streptozocin (STZ) at a dose of 40 mg/kg. Chronic hypoxia was induced by placing dams (groups IV, V and VI) in conditions of 10.5% oxygen and 89.5%. Insulin was administered subcutaneously at the dose of 9 IU/kg. Starting from the 6th day after STZ injection and chronic hypoxia conditions animals were caged together for 12 hours for 3 consecutive days to ensure fertilization. On day 21 of gestation the animals were decapitated, the fetuses were removed and weighted. Results: Mean fetal body weight in separate groups were: I — 5.38 g, II — 6.04g, III — 5.32g, IV— 5.56 g, V — 3.45 g, VI — 6.23 g. Conclusions: Pre-existing type 1 diabetes does not affect fetal body weight compared to healthy newborn control rats. Pro­longed hypoxia does not impact on fetal body weight. Chronic hypoxia during pregnancy complicated with untreated type 1 diabetes mellitus leads to significant reduction of fetal body weight. Insulin treatment reversed the detrimental effect of chronic hypoxia on fetal development.

Background Abnormal retinoic acid (RA) signalling is considered a major cause of congenital diaphragmatic hernia (CDH). Pulmonary hypoplasia and pulmonary hypertension are the major causes of morbidity and mortality in infants born with CDH. Experimental studies in animals have found that RA signalling is involved in lung and liver development, but animal models of CDH do not directly correlate with CDH in human fetuses. This study investigated if RA status is also linked to lung and liver growth in human fetuses with CDH. Study design and patients Hepatic stellate cells (HSC) in autopsy human fetal liver tissue were identified using cRBP-1 immunohistochemistry and the numbers of HSC manually counted. In mammals, RA is principally stored in HSC complexed to cRBP-1 and therefore cRBP-1+ HSC numbers were used as an indicator of fetal RA status. The number of HSCs was correlated with liver and lung weights, calculated relative to either normal biometric values or fetal body weight. Results The number of cRBP-1+ HSCs correlated with lung weight contralateral to the side of the diaphragmatic hernia (r = 0.82, p = 0.025) and combined lung weight (r = 0.78, p = 0.039) but not with ipsilateral lung weight (r = 0.43, p = 0.33), in fetuses with right and left CDH and a case of giant omphalocoele. Liver growth was influenced by contact with diaphragm but not significantly correlated with cRBP-1 expression (r = 0.52, p = 0.056). Conclusion Fetal RA stores, reflected in the number of cRBP-1+ HSCs, influence lung growth as well as diaphragm development in human fetuses with CDH. Contact with diaphragm influenced liver growth.

Objective To examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth. Methods Pregnant rats were exposed to a severe hypoxia (9.5%-10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student's t test and simple regression were used for statistical analysis. Results As the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count. Conclusion In a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.

Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6–18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight.

Maternal exercise during pregnancy has been shown to improve the long‐term health of offspring in later life. Mitochondria are important organelles for maintaining adequate heart function, and mitochondrial dysfunction is linked to cardiovascular disease. However, the effects of maternal exercise during pregnancy on mitochondrial biogenesis in hearts are not well understood. Thus, the purpose of this study was to test the hypothesis that mitochondrial gene expression in fetal myocardium would be upregulated by maternal exercise. Twelve‐week‐old female C57BL/6 mice were divided into sedentary and exercise groups. Mice in the exercise group were exposed to a voluntary cage‐wheel from gestational day 1 through 17. Litter size and individual fetal weights were taken when pregnant dams were sacrificed at 17 days of gestation. Three to four hearts from the same group were pooled to study gene expression, protein expression, and enzyme activity. There were no significant differences in litter size, sex distribution, and average fetal body weight per litter between sedentary and exercised dams. Genes encoding mitochondrial biogenesis and dynamics, including nuclear respiratory factor‐1 (Nrf1), Nrf2, and dynamin‐related GTPase termed mitofusin‐2 (Mfn2) were significantly upregulated in the fetal hearts from exercised dams. Cytochrome c oxidase activity and ATP production were significantly increased, while the hydrogen peroxide level was significantly decreased in the fetal hearts by maternal exercise. Our results demonstrate that maternal exercise initiated at day 1 of gestation could transfer the positive mitochondrial phenotype to fetal hearts.

Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6–15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6–20 pregnant days were significantly different (P < 0.01, P < 0.05). Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group (P < 0.05), while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects.

The aim of the present study was to conduct a preliminary screen of neem, a valuable plant source commonly used in traditional medicine and in modern drug development, to determine its potential for reproductive toxicity. Neem bark extract at dose 50, 100 and 300 mg/kg bodyweight was administered by gavage to pregnant rats daily from gestational day 1 to 20. Implantation rate, fetal mortality, fetal body weight and length, external and skeletal abnormalities, micronucleus assay in fetal liver cells, as well as histological and ultrastructural examination of fetal liver, were studied. On the other hand, maternal body weight, absolute and relative organs weight, micronucleus assay in bone marrow, histological and cytological examination of liver, and certain parameters related to liver function (serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities, as well as total protein, albumin and globulin content) were determined in mothers. No effects were observed on reproductive outcomes or dams received dose of 50 or 100 mg/kg body weight, except some histological and cytological liver defects were observed at 100 mg/kg body weight. Neem bark extract administered at dose 300 mg/kg body weight was associated with reduced fetal body weight, minor skeletal variations, and moderate histological and ultrastructural alterations in the liver. However, no considerable adverse effect on implantation, mortality rate, external malformation, or in frequency of micronucleated polychromatic erythrocytes in fetal liver cells was observed. In dams exposed to the high dose, significant physiological, histological and cytological alterations in liver were observed without affecting body weight, organs weight, or bone marrow micronuclei rate. In conclusion, neem bark extract was not teratogenic or genotoxic in rats. It has a low potential to adversely affect prenatal development only at maternally toxic dose.

Article History Rauwolfia vomitoria is a plant used in the treatment of hypertension, schizophrenia, and insomnia among others. This study investigated the effects of Rauwolfia vomitoria on the histology of the fetal lungs. Fifteen female Wistar rats weighing 180-200 g were divided into three groups (A, B, and C), consisting of five rats each. The animals mated overnight at estrous and the morning after coitus was designated day zero of pregnancy. Oral doses of 150 mg/kg and 250 mg/kg of ethanolic leaf extract of Rauwolfia vomitoria were administered to pregnant rats in groups B and C, respectively on day 7-11 of gestation, while group A served as the control group and were given distilled water. On day 20 of gestation, the rats were sacrificed and their fetuses examined and weighed. Fetal body weight, crown-rump and tail lengths were measured. Result showed significant (P < 0.05) higher anthropometric parameters, and the histological observations of the fetal lungs showed marked distortion of the normal lung cytoarchitecture in the treated groups compared to the control. These results suggest that doses of 150 mg/kg and 250 mg/kg body weight of the leaf extract of Rauwolfia vomitoria may cause intrauterine growth acceleration and may be pneumotoxic to the developing rat's lungs with the effect being dose dependent

The safety of a “core” version of esterified propoxylated glycerols (EPGs) was assessed in a developmental toxicity study in New Zealand white rabbits, Hra:(NZW)SPF. Four groups each of 18 inseminated female rabbits received diets ad libitum containing concentrations of 0%, 2.5%, 5%, and 10% EPG (w/w) with 6% corn oil (w/w). No treatment-related effects were observed in any maternal toxicity parameter, including maternal body weight and weight gain, feed consumption, or clinical signs of toxicity. There were no statistically significant treatment-related effects in gestational parameters, including pre- and post-implantation loss, litter size, sex ratio, fetal body weight, and crown–rump length. The incidences of fetal external, visceral, and skeletal malformations or variations were also comparable across groups. A no-observable-adverse-effect level (NOAEL) of 10% EPG (approximately 4.76 g/kg bw/day) for both maternal and developmental toxicity is proposed based on the results of this study.

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (

The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary–gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect. While PnCDF, at a dose sufficient to cause a reduction in fetal LH, provoked defects in sexual behavior at adulthood, a dose less than the ED{sub 50} failed to produce any abnormality. There was a loss of fetal body weight following in utero exposure to PnCDF, and the effect of PnCDF was also much less than that of TCDD. The disturbance in fetal growth was suggested to be due to a reduction in the level of fetal growth hormone (GH) by dioxins. The disorder caused by PnCDF/TCDD in the fetal pituitary–gonad axis occurred at doses less than those needed to cause wasting syndrome in pubertal rats. The harmful effect of PnCDF relative to TCDD was more pronounced in fetal rats than in pubertal rats. These lines of evidence suggest that: 1) PnCDF as well as TCDDmore » imprints defects in sexual behavior by disrupting the fetal pituitary–gonad axis; 2) these dioxins hinder fetal growth by reducing the expression of fetal GH; and 3) the fetal effects of PnCDF/TCDD are more sensitive than sub-acute toxicity during puberty, and the relative effect of PnCDF varies markedly depending on the indices used. - Highlights: • 2,3,4,7,8-Pentachlorodibenzofuran (PnCDF) lowers gonadal steroidogenesis in fetuses. • PnCDF exerts the above effect through an initial attenuation in gonadotropin level. • PnCDF imprints sexual immaturity by transiently disrupting the pituitary–gonad axis. • PnCDF also disturbs pup growth probably due to a reduction in growth hormone level. • The above effects are far lesser in PnCDF than 2,3,7,8-tetrachlorodibenzo-p-dioxin.« less

In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg−1·day−1) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), β-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes.

The aim of this in vivo experimental study is to determine the association between ultrasound exposure time and rabbit fetal weight. A total of 14 pregnant does were exposed to ultrasound heating for 30, 60, and 90 minutes of ultrasound exposure at their middle of each gestational stage, while another 4 pregnant does served as control. Total of 136 fetuses (1st stage, n=34 (25%); 2nd stage, n=28 (20.6%); 3rd stage, n=74 (54.4%)) were analyzed for fetal body weight. There were significant differences in fetal weight at all stages (p

While the impact of alcohol consumption by pregnant women on fetal neurodevelopment has received much attention, the effects on the cardiovascular system are not well understood. We hypothesised that repeated exposure to alcohol (ethanol) in utero would alter fetal arterial reactivity and wall stiffness, key mechanisms leading to cardiovascular disease in adulthood. Ethanol (0.75 g (kg body weight)(-1)) was infused intravenously into ewes over 1 h daily for 39 days in late pregnancy (days 95-133 of pregnancy, term ∼147 days). Maternal and fetal plasma ethanol concentrations at the end of the hour were ∼115 mg dl(-1), and then declined to apparent zero over 8 h. At necropsy (day 134), fetal body weight and fetal brain-body weight ratio were not affected by alcohol infusion. Small arteries (250-300 μm outside diameter) from coronary, renal, mesenteric, femoral (psoas) and cerebral beds were isolated. Endothelium-dependent vasodilatation sensitivity was reduced 10-fold in coronary resistance arteries, associated with a reduction in endothelial nitric oxide synthase mRNA (P = 0.008). Conversely, vasodilatation sensitivity was enhanced 10-fold in mesenteric and renal resistance arteries. Arterial stiffness was markedly increased (P = 0.0001) in all five vascular beds associated with an increase in elastic modulus and, in cerebral vessels, with an increase in collagen Iα mRNA. Thus, we show for the first time that fetal arteries undergo marked and regionally variable adaptations as a consequence of repeated alcohol exposure. These alcohol-induced vascular effects occurred in the apparent absence of fetal physical abnormalities or fetal growth restriction.

The present study was undertaken to assess the embryotoxic effects due to exposure to nickel (Ni2+) as NiCl2·6H2O in Swiss albino mice. Nickel was administered orally (46, 92, or 185 mg Ni/kg body weight (b.wt.)) from zeroth to fifth day of gestation on the basis of LD50. Dams were sacrificed by cervical dislocation on day 18 of gestation and uteri examined. A significant decrease in maternal and fetal body weight was noted at doses of 92 and 185 mg Ni/kg b.wt. Developmental toxicity was evidenced by a dose-dependent significant reduction in the number of implant sites and live fetuses per dam, increase in the number of resorptions as well as post-implantation deaths. A significant decrease in placental weight was also evident at 185 mg Ni/kg b.wt. Exposure increased skeletal aberrations including absence/reduced ossification of nasal, frontal, parietal, intraparietal, supraoccipital bones of skull, reduced number of ribs, sternebrae and caudal vertebrae, absence/reduced ossified carpals, metacarpals, tar...

Cadmium is a heavy metal and widespread environmental toxicant. This study investigated the effects of prenatal Cd exposure on fetal growth and limb development in rats. Pregnant rats were given 0, 4 or 8 mg/kg/day (equivalent to ≈ 0, 30 or 60 ppm) of cadmium as CdSO4 in their drinking water from conception to gestation day 20. Cd significantly (p

Recent evidence shows that excess nicotinamide can cause epigenetic changes in developing rats. The aim of the present study was to investigate the effects of maternal nicotinamide supplementation on the fetus. Female rats were randomised into four groups fed a standard chow diet (control group) or diets supplemented with 1 g/kg of nicotinamide (low-dose group), 4 g/kg of nicotinamide (high-dose group) or 4 g/kg of nicotinamide plus 2 g/kg of betaine (betaine group) for 14–16 d before mating and throughout the study. Fetal tissue samples were collected on the 20th day of pregnancy. Compared with the control group, the high-dose group had a higher fetal death rate, and the average fetal body weight was higher in the low-dose group but lower in the high-dose group. Nicotinamide supplementation led to a decrease in placental and fetal hepatic genomic DNA methylation and genomic uracil contents (a factor modifying DNA for diversity) in the placenta and fetal liver and brain, which could be completely or partially prevented by betaine. Moreover, nicotinamide supplementation induced tissue-specific alterations in the mRNA expression of the genes encoding nicotinamideN-methyltransferase, DNA methyltransferase 1, catalase and tumour protein p53 in the placenta and fetal liver. High-dose nicotinamide supplementation increased fetal hepatic α-fetoprotein mRNA level, which was prevented by betaine supplementation. It is concluded that maternal nicotinamide supplementation can induce changes in fetal epigenetic modification and DNA base composition. The present study raises the concern that maternal nicotinamide supplementation may play a role in the development of epigenetic-related diseases in the offspring.

R,R-Monatin is an intensely sweet substance originally identified in the root bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as "arruva", has potential for use as a high-potency sweetener food ingredient. Previously, arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD) rats and Crl:CD-1(ICR) mice fed up to 35,000 ppm arruva in the diet for 90 days. In the present study, groups of mated Sprague-Dawley rats (25 Crl:CD(SD) females/group) were exposed continuously to 0 (control), 15,000, 30,000, or 50,000 ppm arruva in the diet during gestation days 6-21. There were no fetal malformations or developmental variations that were attributable to arruva at any exposure level, nor were there any test article-related effects on intrauterine survival. Maternal toxicity, evidenced by lower mean body weights, body weight gains and feed efficiency, was observed at 50,000 ppm. A developmental effect, in the form of lower mean fetal body weight, was noted in the 50,000 ppm group in the presence of maternal toxicity. Therefore, the dietary no-observed-adverse-effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of arruva in pregnant rats during gestation days 6-21 was 30,000 ppm (equivalent to 2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.

Excess L-tryptophan (L-Trp) in the diet decreases fetal body weight. However, the relationship between L-Trp concentration and its effects on maternal, placental, and fetal growth are not well-understood. We investigated the effects of excess L-Trp intake on maternal, placental, and fetal growth. Female mice were fed a 20% casein diet (control diet) or control diet plus 2% or 5% L-Trp during gestation. Pup weights did not differ between the control (L-Trp intake: 0.04 g/kg body weight (BW)/day) and 2% L-Trp groups (L-Trp intake: 3.3 g/kg BW/day), but were significantly lower in the 5% L-Trp group (L-Trp intake: 7.0 g/kg BW/day) than in the control and 2% L-Trp groups. These results show that less than 3.3 g/kg BW/day L-Trp intake in pregnant mice during gestation does not affect fetal growth or L-Trp homeostasis in the placenta or fetus.

The present study’s purpose was to examine the size and location of the thyroid gland using anatomic dissection methods on fetal cadavers. This study was performed on 200 spontaneously aborted human fetuses (100 males and 100 females) aged between 9 and 40 weeks of gestation. Fetuses without any external and internal pathology or anomaly were included in this study. Fetuses were divided into four groups based on gestational ages as follows: first group 9–12 weeks (first trimester), second group 13–25 weeks (second trimester), third group 26–37 weeks (third trimester) and fourth group 38–40 weeks (full term). The fetuses were also grouped into monthly cohorts as follows: 9–12 weeks, 3rd month; 13–16 weeks, 4th month; 17–20 weeks, 5th month; 21–24 weeks, 6th month; 25–28 weeks, 7th month; 29–32 weeks, 8th month; 33–36 weeks, 9th month; and 37–40 weeks, 10th month. The anterior necks of fetuses were dissected and the thyroid glands exposed. Vertebral and laryngeal levels and the dimensions (width, length, thickness and weight) of the fetal thyroid glands were determined by anatomical dissection methods. The dimensions and ratios of the fetal thyroid gland (weight/fetal body weight) were evaluated. The mean values and standard deviations of all parameters by gestational weeks, months, and trimesters were calculated. It was found that all parameters increased with gestational age. No significant differences were observed between genders in all parameters (P > 0.05). There were no significant differences between the right and the left sides for parameters of the thyroid glands. The levels of the superior poles of the thyroid lobes were located at the cervical (C) C1–C3 vertebral bodies. The levels of the inferior poles of the thyroid lobes were located at C4–C5 vertebral bodies. The levels of the superior poles of thyroid lobes were located between the upper ½ and lower ½ of the thyroid cartilage or cricoid cartilage. The levels of the inferior poles of the thyroid lobes were located between the second and sixth tracheal rings. The distance between the superior poles of the thyroid gland and the hyoid bone increased throughout the fetal period. The dimensions of fetal thyroid glands increased with gestational age. The ratio between thyroid gland weights and fetal body weights was unchanged during the fetal period. We believe that the results obtained from this study will be useful in monitoring thyroid glands in the intrauterine period as well as recognizing early diagnosis and treatment of thyroid anomalies. It will also contribute to future studies in obstetrics, perinatology, and fetopathology.

This study evaluates the developmental toxicity of two high molecular weight dialkyl phthalate esters, diundecyl phthalate (DUDP) and ditridecyl phthalate (DTDP). Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1g/kg/day of DUDP or DTDP, by gavage, on gestation days 6-20. DUDP and DTDP had no adverse effects on maternal body weight and food consumption. The number of live fetuses, percent of post-implantation loss and of resorptions, fetal sex, and fetal body weights were not affected by either phthalate. There was no evidence of teratogenicity, whatever treatment. Small decreases in the anogenital distance of male fetuses were noted at 0.5 and 1g DUDP/kg/day. The incidence of fetuses with supernumerary lumbar ribs was significantly higher than control at 0.5 and 1g DUDP/kg/day. Thus, DTDP was not developmentally toxic up to 1g/kg/day and there were signs of DUDP-induced fetal effects at 0.5 and 1g/kg/day.

Venlafaxine (VEN), a newer antidepressant of serotonin and noradrenaline reuptake inhibitor (SNRI) class, is commonly used worldwide for clinical management of various forms of depression even during pregnancy. The maternal and fetal safety of this drug has not been established well so far due to lack of metanalysis studies in clinical settings and controlled investigations in rodents as well as availability of contradictory information. Therefore, present study has been planned to investigate the maternal toxicity in relation to food intake and body weight gain; fetal toxicity as fetal weight at GD-19 and neonatal weight at birth; and postnatal development/growth in young-adult rat offspring. In this study selected doses of VEN (25, 40 and 50 mg/kg) were administered to pregnant rats from GD 5–21 through gavage. These doses were equivalent to human therapeutic dose range (75–375 mg/day). Maternal food intake and body weight gain were found substantially reduced due to drug induced hypophagia. The fetal body weight at GD-19 as well as neonatal birth weight of VEN exposed offspring was found significantly deficient which could not reach up to the control level till 8 weeks as compared to control. This study concludes that prenatal exposure of VEN not only induced maternal weight loss and food intake deficit but also induced long-lasting impact on fetal as well as neonatal development and growth in young-adult offspring. Further, cautions are required for weighing the risks and benefits to both fetus and pregnant mothers before recommendation of SNRIs in general and VEN in particular.

The purpose of the present study was to collect the background data on Wistar Hannover [Crl:WI(Han)] (hereafter Wistar Han) rats in embryo-fetal development studies from the 6 safety research facilities of pharmaceutical companies and contract research organizations. In each facility, 20 or 22 female rats were dosed with vehicle solution during the organogenesis period. As a result, no abnormalities in clinical signs and necropsy findings in dams were found. Body weights and food consumption in dams were lower than those in Sprague Dawley (SD) rats. The number of corpora lutea (13.3 vs. 16.0 in SD) and implantations (11.8 vs. 14.7) were fewer, and fetal body weights (3.66 vs. 3.70) and placental weights (0.42 vs. 0.45) tended to be lower than those in SD rats. Regarding the fetal abnormalities, the incidence of several findings such as the persistent left umbilical artery (10.4% vs. 1.1%) and cervical (5.2% vs. 0.4%), full (7.4% vs. 0.9%) or short supernumerary (64.5% vs. 9.9%) and wavy ribs (6.6% vs. 0.3%) was higher than that in SD rats. Our present study showed that they maintained a sufficient number of live fetuses and the difference in the fetal sex ratio was not observed. In conclusion, Wistar Han rats were considered to be a suitable strain for embryo-fetal development toxicity study. Since the incidence of several abnormalities was higher than that in SD rats, it may be said that to accumulate background control data is important to evaluate the embryo-fetal development toxicity study using Wistar Han rats.

Phenylethyl alcohol (PEA) was tested for developmental toxicity. Pregnant rats were fed 0, 83, 266, or 799 mg/kg/d PEA on gestation days (GDs) 6 to 15; only minimal, nonsignificant effects were observed. In dermal studies, PEA (neat) was applied to the skin on GDs 6 to 15 at dosages of 0, 140, 430, or 1400 mg/kg/d and at 0, 70, 140, 280, 430, or 700 mg/kg/d in a corroborative study. Observations included maternal and embryo-fetal toxicity/abnormalities at 1400 mg/kg/d, increased incidences of rudimentary cervical ribs at ≥430 mg/kg/d, and reduced fetal body weights at ≥140 mg/kg/d. Dermal maternal and developmental no-observed-adverse-effect levels are 70 mg/kg/d, based on dermal irritation and reductions (nonsignificant) in fetal body weights. Human exposure from fragrances is 0.02 mg/kg/d, resulting in a margin of safety >2600, when marked differences in dermal absorption between rats and humans are considered. Under normal fragrance use conditions, PEA is not a developmental toxicity hazard for humans.

OBJECTIVE To document the neonatal outcomes of preterm birth in twin pregnancies and to investigate whether perinatal and obstetric parameters are associated with clinical outcomes. METHODS This retrospective trial was conducted on data gathered from 176 preterm twins delivered in the obstetrics and gynecology department of our tertiary care center. Data extracted from medical files of 88 pregnant women who gave preterm birth (at 26(0/7) to 36(6/7) gestational weeks) to twins were analyzed. Maternal/fetal descriptive and obstetric parameters, sonographic data, route of delivery, indication for cesarean section, birth weight, Apgar scores, head circumference, umbilical cord length and placental weight were noted. RESULTS The average age of the pregnant women was 28.8±6.4 years and ultrasonographic gestational age was 31.9±2.6 weeks. Apgar scores at 1(st) minute were affected significantly by fetal body weight (p=0.001), gestational age (p=0.001), height (p=0.004) and head circumference (p=0.011). None of these variables exhibited a noteworthy effect on Apgar scores at 5(th) minute. CONCLUSION Efforts must be made to achieve advancement of gestational age until delivery in the follow-up preterm of twins. A well-established algorithm with special emphasis to risk factors is necessary to standardize and popularize the appropriate management strategy.

With respect to hazard classification for developmental toxicity under the CLP Regulation it is important to consider the possible influence of maternal toxicity. The aim of the present review was to characterize to which extent developmental effects could be caused by non-specific maternal toxicity. Such effects would not be relevant for classification. In prenatal developmental toxicity studies, the administration of high doses is given in the guideline. The associated non-specific systemic toxicity often affects the maternal body weight. Therefore, published results of studies in rats and rabbits, where maternal weight gain during gestation was inhibited by restricted feeding, were examined regarding developmental effects. In summary, maternal feed restriction resulted in a reduction of fetal body weight that was sometimes accompanied by delayed ossification in both species. Considering their magnitude these effects could be interpreted as secondary non-specific (i.e. not caused by a developmental toxicant) effects. Based on the limited number of available publications in total no further consequences on prenatal development by maternal feed restriction were observed.

Made available in DSpace on 2018-12-11T17:09:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-06 Ethnopharmacological relevance Croton urucurana presents several beneficial pharmacological properties. In Brazil, women who intend to interrupt the pregnancy indiscriminately use extracts of this plant as an abortifacient agent. Aim of study To evaluated the effect of aqueous extract of Croton urucurana latex on the maternal-fetal repercussions in rats. Methods Pregnant rats were randomly distributed into four experimental groups: Control=treated with water (vehicle); Treated 200=treated with a dose 200 mg/kg; Treated 400=dose 400 mg/kg and; and Treated 800=dose 800 mg/kg. The rats were orally treated by gavage with Croton urucurana or vehicle (water) during whole pregnancy. At term of pregnancy, all rats were killed to obtain maternal blood and tissues samples and fetal weight and anomaly analyses. Results C. urucurana treatment (Treated 400 and Treated 800) showed elevated liver enzymatic activities, reduced fetal body weight and placental efficiency. The Treated 800 group presented increased maternal total protein and cholesterol levels, and heart relative weight. All treated groups presented reduced maternal body weight and food intake, and increased pre-implantation loss rate compared to those of Control group. In addition, the treatment contributed to increased skeletal and visceral anomalies with higher doses. Conclusion Croton urucurana treatment caused maternal toxicity, which contributed for impairment embryo fetal development. These results showed that the indiscriminate use of plants during pregnancy should be avoided to prevent potential risk on maternal health as well as their offspring. Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Laboratory of Experimental Research on Gynecology and Obstetrics Graduate Course of Gynecology Obstetrics and Mastology Univ Estadual Paulista_Unesp Laboratory of Experimental Research on Gynecology and Obstetrics Graduate Course of Gynecology Obstetrics and Mastology Univ Estadual Paulista_Unesp

Present study was carried out to determine the effect of aluminum containing antacid on the intrauterine growth and development of fetus. The duration of exposure was also correlated with the effects on fetal morphology and their weights. Seventy-two pregnant mice were given a daily i.e., dose of 0.7mg/100g of aluminum sulphate for various periods according to the grouping of experimental design. This dose was equivalent to maximum therapeutic dose of aluminum salt for a 70 kg man i.e. 5000mg aluminum/day. Fetal examination was performed on day 20 of gestation. The number of live and dead fetuses in the treated animals was not significantly different from the control groups. Therefore embryo lethality of aluminum cannot be induced. However there was a decrease in fetal body weight that was directly related to the duration of exposure to aluminum sulphate solution. Dissecting microscopic examination showed, the development was arrested in the groups exposed to drugs for longer periods. These results revealed that aluminum is a type of heavy metal, which is teratogenic for mammals even in doses, which are nontoxic for adults.

With the limited but ongoing usage of di-n-butyl phthalate (DBP) as plasticizer, the health effects of both phthalate and its alternatives are far from being understood. Multigenerational effects of phthalates were evaluated in rats upon exposure to DBP, aiming to provide some evidences about its potential in causing developmental teratogenicity. Gestational rats were exposed to DBP (500 mg/kg bw/day) and control groups with olive oil. On the 18th day of gestation, fetuses (F1) isolated from a few dams were subjected to prenatal screening, and the other rats were allowed to litter, and later postnatal screening was made. DBP-toxicated (F1) rats were crossed and reared up to three generations (F2 and F3) by adopting the same experimental design. A considerable decrease in the weight of placenta, low number of corpora lutea and increased resorptions, and pre- and postimplantation loss were observed in F1, F2, and F3 generations. Further, there was a decrease in the number of live births and fetal body weight with high mortality, the developmental indices showed reduction in litter size and sex ratio, and a considerable incidence of skeletal and malformation complex involving face and eye was observed in later generations compared to the first. The pre-weaning indices in neonates showed a considerable delay in physical growth milestones and poor scores in sensory motor development. Alterations noticed in the levels of thyroid profile and testosterone found to have a role in sensory motor, craniofacial development, and eye formation. In brief, results confirm multigenerational and fetotoxic effects of DBP; thereby, findings imply that developing tissues are the targets and endocrine disruption appears to be the underlying mechanism of phthalate action.

Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs) are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development.Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E) 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was testedin vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culturein vitro.Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damagein vivo.In vitroexperiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression.Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

The present work was planned to investigate the role of Pectin in ameliorating the morphometric, morphological and skeletal changes induced by mercury in albino rat's fetuses. 50 Wistar wistar virgin female rats were used in the present study and 25 males for mating. The results of the present work showed that the exposure of the pregnant rats to mercury chloride at a dose 5mg/kg body weight lead to significant decrease in fetal body weights as well as body and tail lengths. Also, mercury chloride administration of the pregnant rats resulted in some changes in experimental morphology of the fetuses. In addition, the fetal skeletal system was affected as follows; increase of the number of non ossified bones in the axial and peripheral systems. Pectin treatment of the pregnant rats improved the fetuses’ morphometric, morphological and skeletal changes.

Prenatal ethanol exposure has been well documented to be one of the etiological factors responsible for intrauterine growth retardation (IUGR). Previous studies have shown that chronic ethanol exposure during pregnancy elevated the basic level of corticosterone in fetus. However, the potential mechanisms behind them are still unclear. The aim of the present study was to investigate the effects of prenatal ethanol exposure on maternal and fetal hypothalamic–pituitary–adrenal (HPA) axis as well as placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), and to clarify the mechanism of ethanol-induced IUGR. Pregnant mice were intragastricly administrated with ethanol at a dose of 6.4 g kg−1 d−1 from day 11 to 17 of gestation and parameters representing fetal growth and development were recorded either. The level of corticosterone in maternal serum was determined by ELISA kit. The mRNA expressions of steroidogenic acute regulatory protein (StAR) and cytochrome P450 cholesterol side chain cleavage (P450scc) both in maternal and fetal adrenal, and placental 11β-HSD-2 were detected by real-time quantitative PCR, respectively. The results showed that fetal body weight significantly decreased, and the incidence of IUGR was obviously increased after prenatal ethanol exposure. Maternal serum corticosterone level was elevated, and the expressions of StAR and P450scc were increased in maternal adrenal while decreased in fetal adrenal. The expression of placental 11β-HSD-2 was significantly reduced. These results suggest that prenatal ethanol exposure induces an inhibition of fetal HPA axis activity and IUGR occurs. The mechanism may be associated with ethanol-induced maternal HPA axis activation and high glucocorticoid condition, which impair the placental barrier, and lead to an overexposure of elevated maternal glucocorticoid to fetus, and eventually result in the inhibition of the fetal HPA axis.

Perfluorooctanoic acid (PFOA) is a persistent pollutant worldwide and even found in human cord blood and breast milk. Some animal studies have reported that PFOA causes developmental toxicity such as fetal weight loss, but the mechanism is still unclear. This study focused on developmental toxicity of PFOA, particularly impacts of PFOA on placental endocrine function such as placental prolactin (PRL)-family hormone gene expression and fetal growth in mouse. Time-mated CD-1 mice were dosed by gavage with 0, 2, 10 and 25 mg/kg B.W/day of PFOA (n-10) dissolved with de-ionized water from gestational day (GD) 11-16. During treatment, body weight of each pregnant mouse was measured daily. On day 16, caesarean sections were performed and developmental data were observed. Three placentas from three different pregnant mice were assigned to each of the following experiments. The mRNA levels of mouse placental lactogen (mPL)-II, prolactin like protein (mPLP)-E, -F and Pit-1α and β isotype mRNAs, a transacting factor of mPLs and mPLPs genes, were analyzed using northern blot, in situ hybridization and RT-PCR, respectively. Maternal body weight gain was significantly declined from GD 13 in the PFOA treated groups compared to control. Developmental data such as fetal and placental weights were significantly decreased in accordance with PFOA dosage. Number of dead fetuses and post-implantation losses were significantly increased in the PFOA-exposed groups. In addition, placental efficiency (fetal weight/placental weight) was significantly reduced in PFOA treated groups in accordance with PFOA dosage. Histopathologic changes were observed in placenta. Dose dependent necrotic changes were observed in both 10 mg and 25 mg PFOA treated groups. Cell frequency of glycogen trophoblast cell and parietal trophoblast giant cell were decreased dose dependently in the junctional zone. In the labyrinth zone, sinusoidal trophoblast giant cell frequency was decreased in the 25 mg PFOA treated group. Also, morphological change such as crushed nuclear (atrophy) of trophoblast cells was observed in 25 mg PFOA treated group. Finally, mRNA levels of the mPL-II, mPLP-E, -F and Pit-1α and β were significantly reduced in the PFOA treated groups dose dependently. In addition, the changing pattern between mPL-II, mPLP-E, -F mRNA levels and fetal body weight showed positive relationship. In conclusion, the inhibitory effects of PFOA on the placental prolactin-family hormone genes expression may be secondary effects to insufficient trophoblast cell type differentiation and/or increased trophoblast cell necrosis. The impacts of PFOA on placental development and endocrine function reduced the placental efficiency and partly contributed to the fetal growth retardation in the mouse.

In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122–124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment.

Objective: To evaluate the status of fertility, developmental stages during gestation and teratological changes, if any, following oral administration of methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya in rats. Materials and Methods: The MSF was administered at the doses of 50 mg contraceptive dose (CD), 100 mg (2x CD), 250 mg (5x CD) and 500 mg (10x CD)/kg body wt/day along with vehicle-treated control using 10 male and 20 female Wistar rats in each group. Necropsies were performed one day before the expected parturition. Status of gravid/non-gravid uterus, the number of corpora lutea in the ovary, implantation status, fetal wellbeing, fetal resorption, fetal body weight, external, visceral and skeletal malformations were recorded. Results: Pregnancies were recorded in vehicle-treated control animals and in the animals treated with 50 mg/kg body wt/day. The animals treated with 2x CD, 5x CD and 10x CD did not get pregnant. The fetuses and the status of the ovary, uterus and implantation, fetal body weight, soft tissues and skeletal structures were recorded normal. Data were comparable to those of control. Conclusion: The results suggest that the test substance had no developmental toxicity and teratogenicity which could affect pregnancy, implantation and gestation.

The work evaluates the possible adverse effects on pregnancy and fetal and offspring development arising from the injection of blood serum from rats exposed to microwaves at a power density of 500 μW/cm2 into intact female rats. The study is performed on 59 pregnant Wistar rats. Intrauterine mortality, embryo and fetal body weights, and placenta weight are used for the evaluation of embryo and fetal development. Generally accepted integral and specific parameters are used for the evaluation of the postnatal development of offspring during the first 30 days of life. It is shown that injection of blood serum from rats subjected to long-term RF exposure at 500 μW/cm2 into intact rats on the tenth day of pregnancy results in adverse effects on fetal and offspring development. Higher total in utero and postnatal mortality, as well as delayed offspring development, are recorded.