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How does progesterone improve fetal outcome and change the expression of placental glucose transporters (GLUT) in dexamethasone-induced intrauterine growth restriction (IUGR)?A total of 64 rats were divided randomly into four different treatment groups based on daily i.p. injections of either saline or dexamethasone in the presence or absence of progesterone. Injections started on the 15th day of gestation (15dg) and lasted until the day of sacrifice at 19dg or 21dg. Maternal plasma progesterone concentrations were measured by enzyme-linked immunosorbent assay. The gene and protein expression of placental GLUT1 and GLUT3 were evaluated in the placental labyrinth and basal zones by real-time polymerase chain reaction and Western blotting, respectively. The localization of GLUT1 and GLUT3 was evaluated by immunohistochemistry.Dexamethasone induced significant decreases in maternal serum progesterone concentrations (P = 0.029) and placental (P 0.001) and fetal body (P = 0.009) weights. Dexamethasone also reduced the expression of GLUT1 in the labyrinth zone (P = 0.028) and GLUT3 in both the labyrinth (P = 0.002) and basal zones (P = 0.026). Coadministration of dexamethasone and progesterone prevented the reduction in fetal body weight, placental weight and placental GLUT expression compared with that seen in dexamethasone-treated groups.These results suggest that progesterone prevents the significant reduction in fetal and placental weights in dexamethasone-induced IUGR, possibly through improving the expression of placental GLUT.

Direct fetal creatine supplementation increased plasma and cerebral creatine concentrations but did not alter fetal body weight, basal cardiovascular output, or blood chemistry. Creatine-treated fetuses displayed changes to arterial oxygenation 24–72 h after acute global hypoxia. An increase in striatum total creatine levels following UCO was also noted and suggests that increasing creatine tissue availability may be an adaptive response against the effects of hypoxia.

Fetal circulation is unique and the parameters describing hemodynamic status during development are critical for constructing a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of circulatory changes during fetal development, with a specific focus on developing these models, has not been reported. The objective of this work was to collate, analyze, and mathematically describe physiological information on fetal cardiac output and tissue blood flows during development. A comprehensive literature search was carried out to collate and evaluate the changes to fetal cardiac output and fetal tissue blood flows during growth. The collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing the average parameter changes and variability during development. Data were available for fetal cardiac output (14 Doppler studies), blood flow through the fetal umbilical vein (15 studies), ductus venosus (6 studies), liver veins (5 studies), brain (4 studies), lungs (5 studies), and kidneys (2 studies). Fetal cardiac output is described as either an age- or weight-dependent function. The latter is preferred as it generates an individualized cardiac output that is correlated to the fetal body weight. Blood flow as a proportion of fetal cardiac output to the liver, placenta, brain, kidneys, and lungs was age varying, whilst for the adipose, bone, heart, muscle, and skin the blood flow proportions were fixed. The pattern of change (with respect to direction and pace) for each of these parameters was different. Despite limitations in the availability of some values, the collected data provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications of these data include predicting xenobiotic exposure and risk assessment in the fetus following the administration of maternally dosed drugs or unintended exposure to environmental toxicants.

Ultrasonography and fetal heart rate monitoring are subjective assessments of fetal condition, which warrants the need for objective markers to predict fetal condition. Urinary L-type fatty acid-binding protein (L-FABP) levels correlate with hypoperfusion. Elevated amniotic fluid L-FABP levels may represent fetal tissue hypoperfusion since the amniotic fluid contains fetal urine. In this study, we aimed to analyze the effectiveness of amniotic fluid L-FABP as a predictor of fetal condition. We classified singleton pregnancies into groups based on fetal growth restriction (FGR) with and without fetal blood flow abnormalities (FGR and healthy-FGR groups, respectively) and the non-FGR group (control group). We collected amniotic fluid at the time of vaginal delivery, cesarean section and amniocentesis, and compared the patient characteristics, clinical outcomes and amniotic fluid levels of L-FABP between the groups. We analyzed 153 singleton pregnancies and 186 amniotic fluid samples (FGR group, 6 (3.9%) pregnancies and 23 (12.4%) samples; healthy-FGR group, 15 (9.8%) pregnancies and 20 (10.7%) samples; control group, 132 (86.3%) pregnancies and 143 (76.9%) samples). The amniotic fluid L-FABP level was significantly higher in the FGR group compared to that in the healthy-FGR and control groups. Multivariate analysis revealed that the amniotic fluid L-FABP level was not affected by fetal body weight. Additionally, the amniotic fluid L-FABP levels increased significantly in cases with fetal blood flow abnormalities or early gestational age. Therefore, amniotic fluid L-FABP level may be an objective and accurate predictive marker of fetal condition.

Objective: To evaluate the effect of norfloxacin on pregnant female rats. Animals: 30 pregnant female rats (170-200 gm of weight and 3.5-4 months age). Design: Randomized controlled study. Procedures: The effect of orally administrated norfloxacin, given twice daily for 10 successive days, on the fetal development in pregnant female rats at therapeutic (35 mg/kg) and double therapeutic (70 mg/kg) doses was investigated in pregnant female rats. At 6th -15th day of pregnancy, 30 females were classified, in groups of ten rats, into 3 groups.Group 1 (control group): rats were given distilled water orally. Group 2: rats were given norfloxacin at a dose rate of 35 mg/kg bwt. Group 3: rats were given norfloxacin at a double therapeutic dose of 70 mg/kg bwt. At 20th day of gestation all pregnant rats were anesthetized to determine the changes; if any; in fetal development (morphological, visceral, skeletal and histopathological examinations) and on treated dams (biochemical parameters of serum and histopathological alterations in placenta, liver and kidney). Results: Administration of norfloxacin, in both doses, to pregnant females decreased the number of viable feti, fetal body weight and crown-rump length, andincreased the number of resorbed feti (P< 0.05).It also induced visceral and skeletal abnormalities in feti. Histopathological examination of internal organs to both dams and feti revealed pathological alterations in liver and kidney of both, and placenta of the dam.Administration of norfloxacin at both therapeutic and double therapeutic doses increased maternal serum transferases levels (ALT and AST), decreased serum albumin and total portein levels, and increased serum levels of urea and creatinine (P< 0.05). Conclusion and clinical relevance: High doses of norfloxacin induce fetal defects and abnormalities in early stage of gestation in rats.

We previously demonstrated decreased placental perfusion, reduced amniotic fluid protein content, and increased pregnancy loss in a nonhuman primate model of gestational protein restriction. Here, our objective was to link these detrimental findings with a functional placental assessment. As blood flow is critical to maternal-fetal exchange, we hypothesized that a protein-restricted diet would impair placental taurine uptake. Pregnant rhesus macaques were maintained on either control chow (CON, n = 5), a 33% protein-restricted diet (PR33, n = 5), or a 50% PR diet (PR50, n = 5) prior to and throughout pregnancy. Animals were delivered on gestational day 135 (G135; term is G168). Taurine activity was determined in fresh placental villous explants. Taurine transporter (TauT) protein expression, placental growth factor (PLGF), and insulin-like growth factor (IGF)-1 and IGF-2 protein concentrations were measured, and histological assessment was performed. Fetal body weights and placental weights were comparable between all three groups at G135. Placental taurine uptake was decreased in PR33- and PR50-fed animals compared to CON, yet TauT expression was unchanged across groups. PLGF was significantly increased in PR50 vs. CON, with no change in IGF-1 or IGF-2 expression in placental homogenate from PR-fed animals. Accelerated villous maturation was observed in all PR50 cases, three of five PR33, and was absent in CON. We demonstrate conserved fetal growth, despite a decrease in placental taurine uptake. Increased expression of PLGF and expansion of the syncytiotrophoblast surface area in the severely protein-restricted animals suggest a compensatory mechanism by the placenta to maintain fetal growth.

Perfluorooctane sulfonate (PFOS) is a metabolic-disrupting chemical. There is a strong association between maternal and cord blood PFOS concentrations, affecting metabolism in early life. However, the underlying effects have not been fully elucidated. In this study, using the maternal-fetal model, we investigated the impact of gestational PFOS exposure on the placental structure and nutrient transport. Pregnant mice were oral gavaged with PFOS (1 or 3 μg PFOS/g body weight) from gestational day (GD) 4.5 until GD 17.5. Our data showed a significant reduction in fetal body weight at high dose exposure. There were no noticeable changes in placental weights and the relative areas of junctional and labyrinth zones among the control and exposed groups. However, a placental nutrient transport assay showed a significant reduction in maternal-fetal transport of the glucose and amino acid analogues. Western blot analysis showed a significant decrease in the expression levels of placental SNAT4 upon PFOS exposure. Moreover, in the high-dose exposed group, placenta and fetal livers were found to have significantly higher corticosterone levels, a negative regulator of fetal growth. The perturbation in the placental transport function and corticosterone levels accounted for the PFOS-induced reduction of fetal body weights.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment, and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 wk before mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. Because high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.\ud\udNEW & NOTEWORTHY We used a mouse model of gestational hypercholanemia to investigate the use of obeticholic acid (OCA), a potent FXR agonist, as a treatment for the hypercholanemia of intrahepatic cholestasis of pregnancy (ICP). The results demonstrate that OCA can improve the fetal bile acid profile. This is relevant not only to women with ICP but also for women who become pregnant while receiving OCA treatment for other conditions such as primary biliary cholangitis and nonalcoholic steatohepatitis.

Background: Diabetes mellitus, one of the most common medical complications, has become a major challenging threat in a pregnant woman. It is associated with various maternal and fetal complications which include polyhydramnios, macrosomia, operative interference, shoulder dystocia, birth injuries and perinatal mortality. Effective treatment of pre-existing as well as gestational diabetes mellitus and early prediction of fatal complications will improve outcome and reduce perinatal mortality. Aim of the study: Evaluate the effect of diabetes mellitus on fetal outcome. Assess role of ultrasound in prediction of fetal complications in late diabetic pregnancy using sonographic fetal parameters. Compare between diabetic and non-diabetic regarding ultrasonographic fetal measurements and occurrence of maternal and fetal complications. Patients and Methods: A prospective study including 82 women with diabetic pregnancy (diabetic group) and 156 pregnant women with normal GTT were included in this study and considered as control group. It was conducted in Boulak El-Dakrour General Hospital over a period of 2 years. Women in both groups were subjected to ultrasonographic examination at 27-28 weeks of gestation and at 36-37 weeks. At each examination fetal anthroprometric parameters, umbilical cord thickness and hemodynamic parameters of umbilical artery were measured. Results: of the present study revealed that: There was significant difference between diabetic and control groups regarding sonographic predictors of fetal macrosomia in term of abdominal circumference, estimated fetal body weight and Wharton's jelly area. Fetuses of mothers in the diabetic group showed statistically significant increase of fetal macrosomia, low birth weight and intrauterine fetal demise in comparison to the control group; the diabetic group showed statistically significant increase of cesarean delivery in comparison to the control group. Conclusion: The results of the present study suggest the possibility of using sonographically determined fetal abdominal circumference, Wharton's jelly area, estimated fetal body weight measurements to distinguish women at high risk for abnormal fetal growth and disproportion potentially resulting in early detection and reducing fetal morbidity. In addition, these parameters can be considered as an effective, noninvasive and cost-effective method that can prove useful for evaluating the fetal consequences of maternal hyperglycemia.

Background Fetal alcohol spectrum disorders (FASD) are preventable adverse outcomes consequent to prenatal alcohol exposure. Supplemental choline confers neuroprotection to the alcohol-exposed offspring, but its actions outside the brain are unclear. We previously reported that prenatal exposure of mice to 4.5 g/kg of alcohol decreased placental weight in females only, but decreased body weight and liver-to-body weight ratio and increased brain-to-body weight ratio in both sexes. Here we test the hypotheses that a lower alcohol dose will elicit similar outcomes, and that concurrent choline treatment will mitigate these outcomes. Methods Pregnant C57BL/6J mice were gavaged with alcohol (3 g/kg; Alc) or maltodextrin (MD) from embryonic day (E) 8.5-17.5. Some also received a subcutaneous injection of 100 mg/kg choline chloride (Alc + Cho, MD + Cho). Outcomes were evaluated on E17.5. Results Alc dams had lower gestational weight gain than MD; this was normalized by choline. In males, Alc decreased placental weight whereas choline increased placental efficiency, and Alc + Cho (vs. MD) tended to further reduce placental weight and increase efficiency. Despite no significant alcohol effects on these measures, choline increased fetal body weight but not brain weight, thus reducing brain-to-body weight ratio in both sexes. This ratio was also lower in the Alc + Cho (vs. MD) fetuses. Alc reduced liver weight and the liver-to-body weight ratio; choline did not improve these. Placental weight and efficiency correlated with litter size, whereas placental efficiency correlated with fetal morphometric measurements. Conclusions Choline prevents an alcohol-induced reduction in gestational weight gain and fetal body weight and corrects fetal brain sparing, consistent with clinical findings of improvements in alcohol-exposed children born to mothers receiving choline supplementation. Importantly, we show that choline enhances placental efficiency in the alcohol-exposed offspring but does not normalize fetal liver growth. Our findings support choline supplementation during pregnancy to mitigate the severity of FASD and emphasize the need to examine choline's actions in different organ systems.

Fetal growth restriction, or low birth weight, is a strong determinant for eventual obesity and type 2 diabetes. Clinical studies suggest placental mechanistic target of rapamycin (mTOR) signaling regulates fetal birth weight and the metabolic health trajectory of the offspring. In the current study, we used a genetic model with loss of placental mTOR function (mTOR-KOPlacenta) to test the direct role of mTOR signaling on birth weight and metabolic health in the adult offspring. mTOR-KOPlacenta animals displayed reduced placental area and total weight, as well as fetal body weight at embryonic day (E) 17.5. Birth weight and serum insulin levels were reduced; however, β cell mass was normal in mTOR-KOPlacenta newborns. Adult mTOR-KOPlacenta offspring, under a metabolic high-fat challenge, displayed exacerbated obesity and metabolic dysfunction compared with littermate controls. Subsequently, we tested whether enhancing placental mTOR complex 1 (mTORC1) signaling, via genetic ablation of TSC2, in utero would improve glucose homeostasis in the offspring. Indeed, increased placental mTORC1 conferred protection from diet-induced obesity in the offspring. In conclusion, placental mTORC1 serves as a mechanistic link between placental function and programming of obesity and insulin resistance in the adult offspring.

Background Silver nanoparticles (SNPs) are being increasingly used in medical and industrial products. The aim of the present study was to evaluate the toxic effect of maternal exposure to SNP (1 mg/kg/day, 70 nm) on fetal development during the first and second weeks of pregnancy. Methods Twenty-four pregnant mice were divided into four groups. SNP was administered by oral gavage on gestational days (GD) 1-7, GD8-14, or GD1-14. Phosphate buffered saline was administered by oral gavage to a control group. On GD15, the uteri were excised, and fetal bodies and placentas were weighed. Head and placental circumferences and fetal crown-rump length were measured, and fetuses were evaluated for external malformation. TUNEL assay was performed to assess apoptosis in the fetal midbrain. Hematoxylin-eosin staining was carried out to determine changes in fetal histomorphology. Fetal liver cells were used for karyotype analysis. Results Significant decreases in fetal body weight, and crown-rump length were observed in SNP-treated groups. Exencephaly, small head, scoliosis, lordosis, short thorax and trunk, also fused digits were detected in SNPs-treated groups. Fibrosis, necrosis, and apoptotic cells in fetal midbrains increased significantly in the GD8-14 and GD1-14 groups compared to the control group. Chromosomal features were not different in fetuses between groups. Conclusions Exposure to 1 mg/kg/day SNP during pregnancy in mice adversely affected on fetal development. The results do suggest a potential risk for humans that needs to be followed up with more definitive investigations.

Malaria in pregnant women is associated with risk of maternal and perinatal morbidity and mortality, and there are few antimalarial drugs considered safe to treat them, so it is necessary to develop safer antimalarial medicines. The goal of this study was to develop an animal model for human malaria during pregnancy by characterizing the maternal and fetal outcomes in malaria infected Swiss mice. For that, in the present study, we evaluated the outcome of pregnancy in Swiss mice infected with Plasmodium berghei ANKAGFP. We observed a reduction of fetal body weight and signs of skeletal ossification retardation in the offspring of mice infected on GD 12. The group of mice infected with malaria presented premature deliveries and histopathology changes consistent with placental malaria. Our study suggests that Swiss Webster mice infected with P. berghei ANKAGFP on GD 12 might be a valuable model to investigate the safety and the efficacy of new antimalarial drugs indicated to pregnant women.

The objective of this study was to assess how exposure to ergot alkaloids during 2 stages of gestation alters fetal growth, muscle fiber formation, and miRNA expression. Pregnant ewes (n = 36; BW = 83.26 ± 8.14 kg; 4/group; 9 groups) were used in a 2 × 2 factorial arrangement with 2 tall fescue seed treatments [endophyte-infected (E+) vs. endophyte-free (E−)] fed during 2 stages of gestation (MID, days 35 to 85 vs. LATE, days 86 to 133), which created 4 possible treatments (E−/E−, E+/E−, E−/E+, or E+/E+). Ewes were individually fed a total mixed ration containing E+ or E− fescue seed according to treatment assignment. Terminal surgeries were conducted on day 133 of gestation for the collection of fetal measurements and muscle samples. Data were analyzed as a 2 × 2 factorial with fescue treatment, stage of gestation, and 2-way interaction as fixed effects. Fetuses exposed to E+ seed during LATE gestation had reduced (P = 0.0020) fetal BW by 10% compared with E− fetuses; however, fetal body weight did not differ (P = 0.41) with E+ exposure during MID gestation. Fetuses from ewes fed E+ seed during MID and LATE gestation tended to have smaller (P = 0.058) kidney weights compared with E− fetuses. Liver weight was larger (P = 0.0069) in fetuses fed E− during LATE gestation compared with E+. Fetal brain weight did not differ by fescue treatment fed during MID (P = 0.36) or LATE (P = 0.40) gestation. The percentage of brain to empty body weight (EBW) was greater (P = 0.0048) in fetuses from ewes fed E+ fescue seed during LATE gestation, which is indicative of intrauterine growth restriction (IUGR). Primary muscle fiber number was lower (P = 0.0005) in semitendinosus (STN) of fetuses exposed to E+ during MID and/or LATE gestation compared with E−/E−. miRNA sequencing showed differential expression (P < 0.010) of 6 novel miRNAs including bta-miR-652_R+1, mdo-miR-22-3p, bta-miR-1277_R-1, ppy-miR-133a_L+1_1ss5TG, hsa-miR-129-1-3p, and ssc-miR-615 in fetal STN muscle. These miRNA are associated with glucose transport, insulin signaling, intracellular ATP, hypertension, or adipogenesis. This work supports the hypothesis that E+ tall fescue seed fed during late gestation reduces fetal weight and causes asymmetrical growth, which is indicative of IUGR. Changes in primary fiber number and miRNA of STN indicate that exposure to E+ fescue fed during MID and LATE gestation alters fetal muscle development that may affect postnatal muscle growth and meat quality.

Key points Maternal undernutrition during gestation alters fetal lung development by impacting surfactant maturation. However, the direction of change remains controversial. We examined the effects of maternal late gestation maternal undernutrition (LGUN) on maternal and fetal outcomes, signaling pathways involved in fetal lung development, pulmonary hemodynamics and oxygen delivery in sheep using a combination of molecular and MRI techniques. LGUN decreased fetal plasma glucose concentration without affecting arterial. Surfactant maturation was not affected; however, main pulmonary artery blood flow was significantly increased in the LGUN fetuses. This is the first study to explore the relationship between in utero MRI measures of pulmonary hemodynamics and lung development. Across all treatment groups, left pulmonary artery blood flow and oxygen delivery were negatively correlated with SFTP-B mRNA and protein expression in late gestation. Abstract Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero. The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery (DO2 ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development. LGUN from 115 d to 140 d gestation significantly decreased fetal body weight, which was normalized by glucose infusion. LGUN and LGUN+G resulted in decreased fetal plasma glucose concentration, with no change in fetal arterial compared to Control. There was no effect of LGUN and LGUN+G on the mRNA expression of surfactant proteins (SFTP) and genes regulating surfactant maturation in the fetal lung. However, blood flow in the main pulmonary artery (MPA) was significantly increased in LGUN, despite no change in blood flow in the left or right pulmonary artery (LPA or RPA) and DO2 to the fetal lung. There was a negative relationship between LPA flow and DO2 to the left lung with SFTP-B and GLUT1 mRNA expression, while their relationship with VEGFR2 was positive. These results suggest that increased pulmonary blood flow measured by MRI may have an adverse effect on surfactant maturation during fetal lung development. This article is protected by copyright. All rights reserved.

Background: Fetal growth restriction is associated with a greater risk of current wheeze or asthma. We explored the underlying mechanism for this association using a mouse model of maternal hypoxia-induced intrauterine growth restriction (IUGR). Aim: Examine the effects of IUGR on fetal ASM layer thickness. Methods: Pregnant mice were housed under hypoxic conditions (10.5% O2) from gestational day (GD) 11-17.5 (IUGR). Following hypoxic exposure, mice were returned to a normoxic environment (21% O2). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). Body and lung weight was assessed: (i) at the end of the hypoxic insult (GD17.5); and (ii) 3-4 days after insult (day of birth). Lungs were fixed and sections stained with haematoxylin & eosin for planimetry, proliferating cell nuclear antigen to assess ASM proliferation, and TUNEL assay to assess ASM apoptosis. The ASM layer thickness was normalised to perimeter of epithelial basement membrane. Results: IUGR offspring were smaller (reduced weight and dimensions) at both ages compared with Control, however, airway size was comparable. At GD17.5, ASM thickness was increased in the IUGR group compared with the Control group and fetal body weight was inversely related to ASM thickness. The effect of maternal hypoxia on ASM thickness was not observed at birth, after the insult had subsided. There was no difference in ASM proliferation between the groups and ASM apoptosis was not detectable. Conclusion: Maternal hypoxia drove fetal growth restriction and this was accompanied by ASM thickening. Prenatal thickening of the ASM in growth restricted individuals may increase susceptibility to asthma.

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty-one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day-fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.

International audience; egou et al. (2012)have reported prenatal alcohol exposure (PAE)-induced reductions of angiogenesis-related proteins in mouse placenta. These effects were associated with striking alterations in microvascular development in neonatal cerebral cortex. Here, we employed a rat model of moderate PAE to search for additional proteins whose placental and fetal cortical expression is altered by PAE, along with a subsequent examination of fetal cerebral cortical alterations associated with altered protein expression. Long-Evans rat dams voluntarily consumed either a 0 or 5% ethanol solution 4 h each day throughout gestation. Daily ethanol consumption, which resulted in a mean peak maternal serum ethanol concentration of 60.8 mg/dL, did not affect maternal weight gain, litter size, or placental or fetal body weight. On gestational day 20, rat placental: fetal units were removed by Caesarian section. Placental protein expression, analyzed by 2D-PAGE - tandem mass spectroscopy, identified a total of 1,117 protein spots, 20 of which were significantly altered by PAE. To date, 14 of these PAE-altered proteins have been identified. Western blotting confirmed the alterations of two of these placental proteins, namely, annexin-A4 (ANX-A4) and cerebral cavernous malformation protein 3 (CCM-3). Specifically, PAE elevated ANX-A4 and decreased CCM-3 in placenta. Subsequently, these two proteins were measured in fetal cerebral cortex, along with radiohistochemical studies of VEGF binding and histofluorescence studies of microvascular density in fetal cerebral cortex. PAE elevated ANX-A4 and decreased CCM-3 in fetal cerebral cortex, in a pattern similar to the alterations observed in placenta. Further, both VEGF receptor binding and microvascular density and orientation, measures that are sensitive to reduced CCM-3 expression in developing brain, were significantly reduced in the ventricular zone of fetal cerebral cortex. These results suggest that the expression angiogenesis-related proteins in placenta might serve as a biomarker of ethanol-induced alterations in microvascular development in fetal brain.

Background Gestational alcohol exposure can contribute to fetal alcohol spectrum disorders (FASD), an array of cognitive, behavioral, and physical developmental impairments. Mammalian target of rapamycin (mTOR) plays a key role in regulating protein synthesis in response to neuronal activity, thereby modulating synaptic plasticity and long-term memory formation in the brain. Based on our previous quantitative mass spectrometry proteomic studies, we hypothesized that gestational chronic binge alcohol exposure alters mTOR signaling and downstream pathways in the fetal hippocampus. Methods Pregnant Sprague-Dawley rats were assigned to either a pair-fed control (PF-Cont) or a binge alcohol (Alcohol) treatment group. Alcohol dams were acclimatized via a once-daily orogastric gavage of 4.5 g/kg alcohol (peak BAC, 216 mg/dl) from GD 5-10 and progressed to 6 g/kg alcohol (peak BAC, 289 mg/dl) from GD 11-21. Pair-fed dams similarly received isocaloric maltose dextrin. Results In the Alcohol group, following this exposure paradigm, fetal body weight and crown-rump length were decreased. The phosphorylation level of mTOR (P-mTOR) in the fetal hippocampus was decreased in the Alcohol group compared with controls. Alcohol exposure resulted in dysregulation of fetal hippocampal mTORC1 signaling, as evidenced by an increase in total 4E-BP1 expression. Phosphorylation levels of 4E-BP1 and p70 S6K were also increased following alcohol exposure. P-mTOR and P-4E-BP1 were exclusively detected in the dentate gyrus and oriens layer of the fetal hippocampus, respectively. DEPTOR and RICTOR expression levels in the fetal hippocampus were increased; however, RAPTOR was not altered by chronic binge alcohol exposure. Conclusion We conclude that chronic binge alcohol exposure during pregnancy alters mTORC1 signaling pathway in the fetal hippocampus. We conjecture that this dysregulation of mTOR protein expression, its activity, and downstream proteins may play a critical role in FASD neurobiological phenotypes.

Growth is dependent on genotype and diet, even at early developmental stages. In this study, we investigated the effects of genotype, sex, and body weight on the fetal muscle transcriptome of purebred Iberian and crossbred Iberian x Large White pigs sharing the same uterine environment. RNA sequencing was performed on 16 purebred and crossbred fetuses with high body weight (340±14g and 415±14g, respectively) and 16 with low body weight (246±14g and 311±14g, respectively), on gestational day 77. Genotype had the greatest effect on gene expression, with 645 genes identified as differentially expressed (DE) between purebred and crossbred animals. Functional analysis showed differential regulation of pathways involved in energy and lipid metabolism, muscle development, and tissue disorders. In purebred animals, fetal body weight was associated with 35 DE genes involved in development, lipid metabolism and adipogenesis. In crossbred animals, fetal body weight was associated with 60 DE genes involved in muscle development, viability, and immunity. Interestingly, the results suggested an interaction genotype∗weight for some DE genes. Fetal sex had only a modest effect on gene expression. This study allowed the identification of genes, metabolic pathways, biological functions and regulators related to fetal genotype, weight and sex, in animals sharing the same uterine environment. Our findings contribute to a better understanding of the molecular events that influence prenatal muscle development and highlight the complex interactions affecting transcriptional regulation during development.

Pregnancy caused by changes in body weight of pregnant women, which is not significantly impact on the growth of the fetus in the womb, experiencing anemia and low birth weight. The purpose of this study analyzed the nutritional needs of pregnant mothers to changes in maternal and fetal body weight in the Village District of RW 02 Petis Duduk Sampeyan Gresik. Analytical study design with cross sectional study design. The population is all pregnant women in the village of RT 02 RW 02 Petis Sitting Sampeyan District of Gresik by 33 people. Sampling sampling techniques with simple random sampling. The instrument uses observation. This variable is the nutritional needs of pregnant women and changes in maternal and fetal body weight. Data were analyzed with the Mann-Whitney test with α = 0.05. The result showed the majority (66.7%) of respondents need good nutrition. Aswell as the vast majority (66.7%) of respondents normal weight. It can be concluded that there is influence the nutritional needs of pregnant mothers to changes in maternal and fetal body weight in the Village District of RW 02 Petis Sitting Sampeyan Gresik. More nurses can improve the promotion program to improve maternal and fetal body weight through promotion and education in local communities about the importance of maternal and fetal weight.

Circulatory changes during gestational development of the human fetus have been considered to be similar to those noted in studies of the lamb fetus. Blood flow measurements derived by Doppler ultrasound and magnetic resonance imaging techniques in human fetuses at various stages of gestation have been compared with those in the lamb. Combined ventricular output relative to fetal body weight does not change significantly with growth in the lamb or human. However, the proportion of cardiac output to the brain increases markedly in the human, but only slightly in the lamb fetus in the latter half of gestation. Cardiac output distribution to other organs also changes little in the lamb, but in the human, there is a marked decrease in the proportion distributed to the placenta and an increase in pulmonary flow. The developmental changes in the distribution of combined ventricular output in the human fetus may modify the responses to circulatory disturbances, such as congenital cardiovascular malformations, dependent on gestation.

Objective Intrauterine growth restriction is a leading cause of perinatal mortality and morbidity. Using enoxaparin may enhance the placental circulation and improve the intrauterine growth. This study was conducted to assess the efficacy and safety of enoxaparin in treatment of intra-uterine growth restriction. Study design 125 women with intrauterine growth restriction were randomized to control group and intervention group (receiving routine high risk pregnancy prenatal care plus daily subcutaneous injection of 40 mg enoxaparin). Prolongation of pregnancy, fetal birth weight, fetal outcome and enoxaparin side effects were compared in 2 groups. Results Baseline characteristics were similar in 2 groups. Mean gestational age at delivery was 36.73(±2.71) in enoxaparin group and 36.85(±2.17) in control group which showed no statistically significant difference. Mean fetal birth weight had also no statistically significant difference in enoxaparin and control group (2370.16 ± 580.72 g versus 2456.07 ± 543.06 g). Rate of betamethasone administration, intubation, NICU admission, sepsis, necrotizing enterocolitis, intra-ventricular hemorrhage, hypoglycemia and low apgar score were similar in two groups. No major adverse effect was seen. Conclusion Enoxaparin did not prolong the pregnancy and fetal birth weight and did not improve the fetal outcome even in patients with impaired baseline Doppler findings.

Intrauterine growth retardation (IUGR) impairs fetal intestinal development, and is associated with high perinatal morbidity and mortality. However, the mechanism underlying this intestinal injury is largely unknown. We aimed to investigate this mechanism through analysis of intestinal autophagy and related signaling pathways in a rat model of IUGR. Normal weight (NW) and IUGR fetuses were obtained from primiparous rats via ad libitum food intake and 50% food restriction, respectively. Maternal serum parameters, fetal body weight, organ weights, and fetal blood glucose were determined. Intestinal apoptosis, autophagy, and the mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. The results indicated that maternal 50% food restriction reduced maternal serum glucose, bilirubin, and total cholesterol and produced IUGR fetuses, which had decreased body weight; blood glucose; and weights of the small intestine, stomach, spleen, pancreas, and kidney. Decreased Bcl-2 and increased Casp9 mRNA expression was observed in IUGR fetal intestines. Analysis of intestinal autophagy showed that the mRNA expression of WIPI1, MAP1LC3B, Atg5, and Atg14 was also increased, while the protein levels of p62 were decreased in IUGR fetuses. Compared to NW fetuses, IUGR fetuses showed decreased mTOR protein levels and enhanced mRNA expression of ULK1 and Beclin1 in the small intestine. In summary, the results indicated that maternal 50% food restriction on gestational days 10-21 reduced maternal serum glucose, bilirubin, and total cholesterol contents, and produced IUGR fetuses that had low blood glucose and reduced small intestine weight. Intestinal injury of IUGR fetuses caused by maternal food restriction might be due to enhanced apoptosis and autophagy via the mTOR signaling pathway.

Maternal high-fat-diet (HFD) consumption during pregnancy decreased fetal body weight and impacted development of hypothalamic melanocortin neural circuitry in nonhuman primate offspring. We investigated whether these impairments during gestation persisted in juvenile offspring and examined the interaction between maternal and early postnatal HFD consumption. Adult dams consumed either a control diet (CTR; 15% calories from fat) or a high-saturated-fat diet (HFD; 37% calories from fat) during pregnancy. Offspring were weaned onto a CTR or HFD at ~8 mo of age. Offspring from HFD-fed dams displayed early catch-up growth and elevated body weight at 6 and 13 mo of age. Maternal and postnatal HFD exposure reduced the amount of agouti-related peptide fibers in the paraventricular nucleus of the hypothalamus. Postnatal HFD consumption also decreased the amount of agouti-related peptide fibers in the arcuate nucleus of the hypothalamus. Postnatal HFD was associated with decreased food intake and increased activity. These results support and extend our previous findings of maternal diet effects on fetal development and reveal, for the first time in a nonhuman primate model, that maternal HFD-induced disturbances in offspring body weight regulation extended past gestation into the juvenile period. Maternal HFD consumption increases the risk for offspring developing obesity, with the developmental timing of HFD exposure differentially impacting the melanocortin system and energy balance regulation. The present findings provide translational insight into human clinical populations, suggesting that profound health consequences may await individuals later in life following intrauterine and postnatal HFD exposure.

Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38–39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.

In healthy pregnancy, glucose and oxygen availability are essential for fetal growth and wellbeing. However, how substrate delivery and fetal uptake are affected in human pregnancy complicated by fetal growth restriction (FGR) is still unknown. Here we show that the human FGR fetus has a strikingly reduced umbilical uptake of both oxygen and glucose. In 30 healthy term and 32 FGR human pregnancies umbilical volume flow (Qumb) and parallel umbilical vein (uv) and artery (ua) blood samples were obtained at elective Caesarean section to calculate fetal glucose and oxygen uptake as Qumb • Δ (uv-ua) differences. Umbilical blood flow was significantly lower in FGR pregnancy (-63%, P, Financial support was obtained by grants from Fondazione Giorgio Pardi, by ASM (Associazione Italiana per lo Studio delle Malformazioni), and by a Grant of the Italian Ministry of University and Research PRIN 2010-2011 prot. 20102chst5_005.

Background: Oral hypoglycemic agents use during pregnancy was assumed to cause fetal macrosomia and skeletal deformities, and maternal complications due to significant transfer across placenta or ineffective control of blood glucose. Objective: This study investigated effects of insulin, metformin and glibenclamide on maternal blood glucose; and fetal crown-rump length, gross malformation and pancreatic histology in pregnant streptozotocin-induced diabetic rats. Methods: Twenty-five pregnant rats of groups 1 to 5 as normal and diabetic controls; and diabetic treated with insulin, metformin and glibenclamide were used. Experimental GDM was induced using 45 and 35mg/Kgbw of intraperitoneal streptozotocin. Results: Metformin, Insulin and Glibenclamide significantly reduced maternal glucose by 140.6mg/dL, 103.2mg/dL and 98.54mg/dl; respectively and showed islets with regular interlobular ducts, islets with some irregular interlobular ducts, and islets with many irregular interlobular ducts in histological fetal pancreatic photomicrographs respectively. This depicts metformin having highest ameliorative effect. There were no significant differences in maternal and fetal body weights, maternal blood glucose between diabetic groups, and fetal gross examination. Conclusion: At the doses used in this research, metformin and glibenclamide showed no adverse effects on maternal and fetal features in the treatment of GDM. Thus, they can be used as safe and inexpensive alternatives to insulin. Keywords: Gestational diabetes mellitus, oral hypoglycemic agents, blood glucose, fetal malformation and fetal pancreatic histology.

The present investigation was conducted to evaluate the teratogenic and developmental toxicity of fluoride and endosulfan alone and in combination in pregnant Swiss albino mice exposed during the organogenetic period (5–14 days) of gestation. Fluoride (25.1 mg/kg body weight in water) and endosulfan (1.8 mg/kg bw by oral intubation) when administered alone and in combination (fluoride 25.1 mg/kg bw + endosulfan 1.8 mg/kg bw) to pregnant mice caused significant teratogenic effects in developing fetuses. There was no maternal mortality but significant decreases in maternal weight gain and numbers of live fetuses and significant increases in numbers of fetal resorption were recorded in the treated groups. The fetal body weight and litter size also decreased significantly in all treated groups. No external malformations were observed in any of the fetuses. The percent of visceral and skeletal anomalies increased in the fetuses of all treated groups. The fetal malformations observed were internal hydrocephaly, microphthalmia, anophthalmia, pulmonary edema, subcutaneous edema, reduced ossification of skull bones, widened cranial sutures, rib anomalies (short, wavy, partially ossified, or absent ribs), and reduced ossification of phalanges. The occurrence of visceral and skeletal malformations was more severe in the combination group, suggesting additive interaction of fluoride and endosulfan in inducing developmental toxicity in Swiss albino mice.

The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.

A series of regulatory studies were carried out to investigate the effects of the FAAH inhibitor BIA 10–2474 on fertility, embryo-fetal toxicity and pre- and post-natal development in rats and rabbits. Despite some reductions in sperm count in rats from 50 mg/kg, there were no major changes in male fertility up to 100 mg/kg. In female rats administered up to GD6, there were increases in pre-implantation loss at 50 and 100 mg/kg but neither post-implantation loss nor early embryonic development was affected. In contrast, when administered to female rats during pregnancy (GD6-GD17), BIA 10–2474 at 75 mg/kg/day reduced food consumption resulting in weight loss, increased post-implantation loss and reduced mean fetal body weight. In rabbits, the same maternal toxicity was seen but there were no effects in this species on post-implantation loss or fetal body weights. There were no teratological effects clearly due to BIA 10–2474 and developmental milestones and behavior of offspring were not affected. When administered during pregnancy and lactation (GD6-PND20), some post-implantation loss was seen from 20 mg/kg/day, but developmental milestones and behavior of the offspring were not affected, although males tended to have lower body weight. Based on these data the NOAEL for parental fertility was established as 50 mg/kg/day, the maternal NOAEL during pregnancy was 25 mg/kg/day in rats and developmental NOAEL was 25 and 75 mg/kg/day in rats and rabbits, respectively. When administered during post-natal development to rats the maternal NOAEL was 6 mg/kg/day. The parental reproductive NOAEL, the NOAEL for viability and growth of the F1 offspring, the F1 parental NOAEL and the F1 reproductive NOAEL were all considered to be 20 mg/kg/day.

Introduction: This study determined risk factors, obstetric comorbidities, and fetal conditions among HIV-positive mothers to improve their maternal care. Methodology: This retrospective case-control study included HIV-positive pregnant women 18 years of age or older and age-, parity-, and delivery method-matched HIV-negative controls between 2011 and 2018. Those who had stillbirth were excluded. Baseline demographics, labor process, CD4 count, plasma HIV viral load, and antiretroviral therapy (ART) regimen were recorded. Fetal conditions were recorded as well. Results: Forty HIV-positive women (45 parities; 22 via NSD, 23 via C/S) were included, with 45 HIV-negative parities as controls. Twenty-nine (72.5%) HIV-positive women had illicit drug use. In the HIV-positive group, 17% received ART prior to first perinatal visit, and 75.6% reached viral suppression pre-delivery. Zidovudine and ritonavir-boosted lopinavir were the majorly prescribed ART. Mild perineal lacerations via NSD were observed in HIV-positive women. Fetal body weight was lower in HIV- and ART-exposed fetuses (2665 vs 3010 g, p < 0.001). Preterm delivery PTB (28.9% vs 8.9%, p= 0.015) and small-for gestational age SGA (28.9% vs 8.8%, p = 0.003) rates were higher in the HIV-positive group. There was no vertical transmission of HIV. Conclusions: HIV-positive women tend to deliver fetuses with low body weight and have higher SGA and PTB rates. Given that most women received zidovudine and protease inhibitors, benefits of newer agents for HIV-positive pregnancies should be studied.

This study examines the relationship between the emotions of mothers and fetal development and explores the modifying effect that family income has on this relationship. Socio-demographic information, maternal depression, stress, positive and negative emotions, and maternal-fetal attachment data were collected at 16&ndash, 20 weeks of pregnancy. Data on fetal body weight and biparietal diameter indicating fetal development were collected at 33&ndash, 35 weeks to observe the longitudinal effects of mothers&rsquo, emotions on fetal development. We divided subjects into two groups: those with more than 150% of the median income were classified as the high-income group and less than 150% as the middle-income group. T-test, correlation analysis, and multiple regression analysis on maternal emotional status and fetal development were performed for each group. A positive correlation was found between maternal-fetal attachment and negative emotion that was associated with the biparietal diameter and fetal body weight only in the middle-income group. Results of the multiple regression analysis were statistically significant, indicating that maternal-fetal attachment was associated with fetal weight. These results show that the management of subjective emotion is associated with healthy development of the fetus and contributes to health equity.

Palbociclib is a selective inhibitor of the cyclin-dependent kinase (CDK) 4/6, approved for the treatment of breast cancer. We assessed the potential effects of oral administration of palbociclib on reproduction and development. There were no effects on female or male fertility indices; however, in the male there was seminiferous tubule degeneration in the testes and secondary findings in the epididymides, lower testicular and epididymal weights, sperm density and motility. Palbociclib was not teratogenic in rats or rabbits; however, in the presence of maternal toxicity (lower maternal body weight gain and food consumption), low fetal body weights were observed in rats and small forepaw phalanges were noted in rabbits. There were, however, no adverse effects on the F1 generation in a pre- and post-natal developmental toxicity study in the rat.

One of the causes of complicating labor is the fetal factor, namely the fetus's size. If it is not treated immediately, it will increase maternal and neonatal mortality rates. Accurate estimation of fetal birth weight in pregnancy and delivery is an important indicator in determining fetal well-being. Birth weight is important to measure before labor starts, which helps anticipate possible complications in pregnancy, childbirth, and the puerperium. The accuracy of estimation of fetal body weight either by measuring the fundal height or other means will affect labor management. One way to predict the estimated fetal weight, including the Dare's Formula method, is to measure the circumference of the mother's abdomen (abdominal girth) in centimeters, the measurement results times the Fundus Uterine Height (TFU) in centimeters, and the modified Niswander formula (1.12 TFU). - 7,7) 100 (gr). The design used in this study is a Quasi Experiment. Assessment The estimated fetal weight obtained from the measurement is then compared with the newborn's body weight (actual body weight). The population in this study were all pregnant women, both primiparous and multiparous. While the sample to be taken must meet the inclusion criteria that have been set. The results of the study were based on statistical tests using independent t-test, it was found that the p value (0.000)

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system.

Limited nutrient availability is a cause of intrauterine growth restriction (IUGR), a condition that has important implications for the well being of the offspring. Using the established IUGR model of maternal fasting in the rat, we investigated mechanisms that control gene expression and mRNA translation in late-gestation fetal liver. Maternal fasting for 48 h during the last one-third of gestation was associated with a 10–15% reduction in fetal body weight and a disproportionate one-third reduction in total fetal liver protein. The fetal liver transcriptome showed only subtle changes consistent with reduced cell proliferation and enhanced differentiation in IUGR. Effects on the transcriptome could not be attributed to specific transcription factors. We purified translating polysomes to profile the population of mRNAs undergoing active translation. Microarray analysis of the fetal liver translatome indicated a global reduction of translation. The only targeted effect was enhanced translation of mitochondrial ribosomal proteins in IUGR, consistent with enhanced mitochondrial biogenesis. There was no evidence for attenuated signaling through the mammalian target of rapamycin (mTOR). Western blot analysis showed no changes in fetal liver mTOR signaling. However, eukaryotic initiation factor 2α (eIF2α) phosphorylation was increased in livers from IUGR fetuses, consistent with a role in global translation control. Our data indicate that IUGR-associated changes in hepatic gene expression and mRNA translation likely involve a network of complex regulatory mechanisms, some of which are novel and distinct from those that mediate the response of the liver to nutrient restriction in the adult rat.

Studies have revealed that impairment of the pregnant body weight reduces the fetal body weight and causes minor changes in skeletal development. The aim of the present study was to assess the effects of maternal feed restriction during pregnancy in offspring immune system development. Pregnant Wistar rats were distributed into 5 groups: 1 control in which dams received food ad libitum and 4 experimental groups in which dams were fed restricted amounts of rodent ration (16, 12, 9, or 6 g/rat/day) from the 6th to 17th gestation day. Teratogenicity was assessed using classical teratological evaluation and developmental immunotoxicology protocols. Maternal body weight gain, fetus weight, and placenta weight were reduced for feed-restricted females from the groups fed 12, 9, and 6 g/rat/day ( p < 0.05). No pup mortality was observed immediately after cesarean sections among the groups, and no visceral or skeletal malformations were detected. An immunoteratological study revealed an increase in the relative weight of the thymus and an increase in the phorbol myristate-acetate solution-induced hydrogen peroxide release by inflammatory cells in 21-day-old pups. Alterations in the delayed-type hypersensitivity response and the humoral immune response against sheep red blood cells were observed in pups from feed-restricted mothers. Feed restriction in Wistar rats during organogenesis did not promote structural malformations but resulted in offspring with lower birth weights and promoted significant changes in the immune responses of the rat pups.

Background Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin–norepinephrine reuptake inhibitors (SSRI/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that in utero exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat. Methods Timed-pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg/kg/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression. Results Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT/Slc6a4) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5-HT2B/Htr2b) and of fibroblast growth factor 8 was induced in fetal hearts. Conclusion In utero venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. © 2016 Wiley Periodicals, Inc. Birth Defects Research (Part A) 106:1044–1055, 2016. © 2016 Wiley Periodicals, Inc.

Objective To evaluate the diagnostic yield of postmortem magnetic resonance imaging (PM-MRI) compared with conventional autopsy in fetuses of early gestational age and low body weight. Methods Fetuses of Results Full datasets were examined of 204 fetuses, with mean gestational age of 20.95 ± 3.82 weeks (range, 12.0-30.7 weeks) and body-weight range of 15.9-1872 g. Body weight was the most significant predictor of diagnostic yield of PM-MRI. There was 95% confidence that 90% of fetuses will show diagnostic images by PM-MRI for all five organ systems when fetal body weight is ≥ 535 g, but Conclusion PM-MRI is highly likely to provide adequate diagnostic images for fetuses with a body weight > 500 g. Below this weight, the diagnostic yield of standard 1.5-T PM-MRI decreases significantly. These data should help inform parents and clinicians on the suitability of performing PM-MRI in fetuses with low body weight. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Limited studies have reported the effect of prenatal alcohol exposure (PAE) on fetal liver development or liver dysfunction. The current review was conducted to systematically review published studies of PAE and liver dysfunction. Pub Med, Embase and Web of Science database were searched using terms of “prenatal alcohol exposure” and “liver” or “fetal alcohol spectrum disease” and “liver”. The pooled effect size of alcohol exposure was assessed by Hedges’s g and 95 % confidence interval (CI) using fixed model or random model depending on the heterogeneity determined by Q test and I 2 statistic. A total of 23 studies were included. The results indicated that gestation alcohol exposure resulted in significant reduction of fetal body weight (Hedges’s g = −6.854 ± 1.149, 95 % CI −9.106 to −4.602, P

Aim of the work: the present work was done to investigate the role of astaxanthin in ameliorating the physiological and teratological effects of aspartame on the pregnant rats and their fetuses. Materials and methods: in this study 70 virgin mature female albino rats (Wistar wistar) were used and 35 males (for mating); pregnancy was ascertained by vaginal smearing. The pregnant rats were injected on days7, 9, 11 and 13 of gestation (organogenesis period). The animals were divided into the following groups: animals of the first group which were intraperitoneally injected with 0.5ml saline (solvent of aspartame); animals of the second were intraperitoneally injected with 0.5 ml olive oil (solvent of astaxanthin). The third group was divided into 2 subgroups, the pregnant rats of the first subgroup were intraperitoneally injected with aspartame (20mg./kg. body weight), the pregnant rats of the second subgroup were intraperitoneally injected with aspartame (40 mg./kg. body weight). Pregnant rats of the 4th group were intraperitoneally injected with astaxanthin (50mg.kg. body weight) 2 hours after aspartame injection by its 2 doses. Results: aspartame at the dose of 40 mg./kg.body weight induced pre- term ( early delivery); however the 2 doses of aspartame resulted in very highly significant decrease in the mean maternal body weight , unequal horns of the uteri and unequal distribution of the fetuses between them , abnormal amount of fats surrounding the 2 horns of the uterus, regions of hemorrhage were present on the external membrane of the uteri ,very highly significant uterine weight decrease , cases of abortion were noticed as well as highly significant increased resorption of the fetuses. Intraperitoneal injection with aspartame at the 2 doses resulted in fetal mortality, very highly significant fetal body weight and length decrease with a significant decrease in fetal tail length. Moreover, aspartame induced fetal morphological changes such as body diminution, exencephaly, cognition of the blood vessels in the head region and cleft lips. The skin seemed thin and fragile in the head region as well as the fore and hind regions; hematoma was obvious beside edema, clubbed fore and hind limbs, kyphosis was obvious beside hernias on some regions of the skin with hypertrophy of some fetuses and protrusion of the viscera outside the body. Aspartame exposure at the 2 doses induced highly significant increase in mean of maternal serum AST activity, very highly significant increase in mean serum GGT and serum creatinine activity. Conclusion-Treatment with astaxanthin induced obvious improvement in all of the physiological and morphological changes caused by aspartame in the pregnant rats and their fetuses.

Copper nanoparticles (Cu NPs) are increasingly used as an animal feed additive in China. In previous studies, it was determined that Cu NPs can penetrate the placental barrier, however, its toxic effects on the fetus have not yet been elucidated. Therefore, in this study, we investigated the potential fetal toxic effects of Cu NPs. Cu NPs were orally administered to pregnant Sprague-Dawley rats from gestation days (GDs) 3–18 at a dose of 60, 120, and 180 mg/kg/day. Cesarean sections were conducted on GD 19. During fetal examination, no toxicities were observed regarding general clinical signs, however, Cu NPs significantly decreased fetal body weight, body length, and liver weights. Cu ions and Cu MPs exhibited similar effects on the fetal development. Cu NPs increased the liver concentration of Cu, and decreased protein levels and Fe in fetuses. Cu NPs also increased oxidative stress and inflammation in the fetus after pregnant rats were exposed to high doses of Cu NPs. Oral exposure to Cu NPs during pregnancy increased Cu concentrations in the fetus, which not only affected fetal development, but also significantly induced oxidative stress and inflammatory responses in fetal liver. Taken together, these findings are valuable to evaluate fetal risk assessment after oral exposure of Cu NPs during pregnancy. Additional comprehensive toxicity studies are deemed necessary to clarify the underlying mechanisms involved.

A number of studies have reported that fine particulate matter (PM2.5) exposure is associated with adverse pregnancy outcomes. Moreover, PM2.5 exposure contributes to changes of gut microbiota. However, influences of PM2.5 exposure during gestation on maternal gut microbiota and pregnancy outcomes were not well understood. Here we performed a study using mice models. Dams were exposed to PM2.5 suspension by intratracheal instillation on gestational day (GD) 3, 6, 9, 12 and 15. Pregnancy outcomes, maternal gut microbiota and short chain fatty acids on GD 18 were all measured. The fetal body weight of PM2.5 group was significantly lower than that of control group (p

The objective of this examination was to explore the impact of gestational caffeine (1,3,7-trimethylxanthine) exposure on the maternofetal thyroid axis and fetal thyroid–cytokine communications during gestation. Pregnant rats (Rattus norvegicus) were intraperitoneally administered caffeine (120 or 150 mg kg(–1)) from gestation day (GD) 1 to 20. Both doses of caffeine resulted in maternal hyperthyroidism, whereas the elevation in the concentration of serum free triiodothyronine (FT3) and free thyroxine (FT4) was related to a depletion in the level of TSH at GD 20. Maternal body weight gain and food consumption were markedly increased, while fetal body weight was significantly reduced. These alterations caused fetal hypothyroidism and several pathological lesions in the fetal thyroid gland including a vacuolar colloid, destructive degeneration, atrophy and hyperplasia at embryonic day (ED) 20. The abnormalities in the fetal thyroid gland seemed to depend on the activation of caspase-3, Bcl-2, BAX, Cox2, and NF-κB mRNA expression. Both maternal caffeine doses caused a marked attenuation in the values of fetal serum GH, IGF-II, VEGF, TGF-β, TNF-α, IL-1β, IL-6, leptin and MCP-1, and a noticeable elevation in the value of fetal serum adiponectin at ED 20. Thus, gestational caffeine exposure might disrupt the fetal thyroid–cytokine axis.

Tartrazine (TAZ) is one of the most commonly used artificial dyes for foods and drugs. We determined the effect of TAZ on fetal development by examining morphological, visceral, and skeletal malformations in rat fetuses following daily oral administration of TAZ to pregnant Wistar rats at the 6th-15th day of gestation. TAZ at 0.45 and 4.5 mg/kg induced 6.0 and 7.1% fetal resorptions, as well as 10.0 and 10.5% fetal mortality, respectively. Fetal body weight and length were significantly lower in the groups treated with TAZ at 0.45 (3.97 ± 0.21 g and 27.3 ± 0.54 mm, respectively) and 4.5 mg/kg (3.48 ± 0.15 g and 23.22 ± 1.02 mm, respectively) than in the control group (4.0 ± 0.15 g and 30.01 ± 0.42 mm, respectively). TAZ at 0.45 and 4.5 mg/kg induced hepatic damage (20 and 33.3%, respectively), dark brown pigmentation due to hemosiderin in the splenic parenchyma (16.7 and 21.7%, respectively), as well as destructed and necrotic renal tubules (16.7 and 26.7%, respectively) in the fetuses. Moreover, TAZ at 0.45 and 4.5 mg/kg caused one or more missing coccygeal vertebrae (20 and 40%, respectively), missing sternebrae (6 and 10%, respectively), missing hind limbs (24 and 4%, respectively), and irregular ribs (16 and 20, respectively) in the fetuses. We concluded that TAZ has embryotoxic and teratogenic potentials in rats.