21st Day Of Gestation Research Articles

The Effect of Prenatal Food Restriction on Brain Proteome in Appropriately Grown and Growth Restricted Male Wistar Rats.

BackgroundFetal growth restriction (FGR) has been associated with a higher risk of developing adverse perinatal outcomes and distinct neurodevelopmental and neurobehavioral disorders. The aim of the present study was to investigate the impact of prenatal food restriction on the brain proteome in both FGR and appropriately grown rats and to identify potential pathways connecting maternal malnutrition with altered brain development.MethodsTen time-dated pregnant Wistar rats were housed individually at their 12th day of gestation. On the 15th day of gestation, the rats were randomly divided into two groups, namely the food restricted one (n = 6) and the control group (n = 4). From days 15 to 21 the control group had unlimited access to food and the food restricted group was given half the amount of food that was on average consumed by the control group, based on measurements taken place the day before. On the 21st day of gestation, all rats delivered spontaneously and after birth all newborn pups of the food restricted group were weighed and matched as appropriately grown (non-FGR) or growth restricted (FGR) and brain tissues were immediately collected. A multiplex experiment was performed analyzing brain tissues from 4 FGR, 4 non-FGR, and 3 control male offspring. Differentially expressed proteins (DEPs) were subjected to bioinformatics analysis in order to identify over-represented processes.ResultsProteomic analysis resulted in the profiling of 3,964 proteins. Gene ontology analysis of the common DEPs using DAVID (https://david.ncifcrf.gov/) showed significant enrichment for terms related to cellular morphology, learning, memory and positive regulation of NF-kappaB signaling. Ingenuity Pathway Analysis showed significant induction of inflammation in FGR pups, whereas significant induction of cell migration and cell spreading were observed in non-FGR pups.ConclusionThis study demonstrated that in both FGR and non-FGR neonates, a range of adaptive neurodevelopmental processes takes place, which may result in altered cellular morphology, chronic stress, poor memory and learning outcomes. Furthermore, this study highlighted that not only FGR, but also appropriately grown pups, which have been exposed to prenatal food deprivation may be at increased risk for impaired cognitive and developmental outcomes.

RETRACTED: A Potential Role of Apelin-13 against Hepatic Injury and Metabolic Disorders in Preeclampsia Induced by L-NAME

Background: Hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia (PE) are exceptionally challenging, as their pathologies and therapeutic management simultaneously influence the mother and embryo, sometimes putting their well-beings at odds with each other. Dysregulated lipid and glucose metabolism may be related to some cases of preeclampsia. Fluctuations in serum apelin levels may be attributed to changes in the serum levels of multiple interrelated factors such as insulin, insulin resistance, inflammatory cytokines, and nephritic damage. Previous studies demonstrated that apelin is an endogenous active peptide with vasodilatory and antioxidative-stress capabilities. Objective: We investigated the relationships among hepatic, nephrotic, and metabolic injuries in different preeclampsia-like mouse models and the potential effect of exogenous apelin administration on hepatic and nephrotic injuries and metabolic disorders in an N-nitro-L-arginine methyl ester (L-NAME) preeclampsia-like Sprague Dawley (SD) rat model. Materials and methods: Forty-three adult female and ten adult male SD rats were involved in this study. The male rats were used to induce pregnancy. The female rats were randomly divided into four equal groups: a non-pregnant group, a normal pregnant group, a group treated with L-NAME to induce preeclampsia, and a group treated with L-NAME and apelin. In all the groups, maternal blood was collected on the 21st day of gestation, and serum samples were used for the determination of systolic blood pressure; the serum uric acid, creatinine, nitric oxide (NO), xanthine oxidase, myeloperoxidase, insulin, glucose, cholesterol, triglyceride (TG), aspartate aminotransferase (AST) and alanine aspartate aminotransferase (ALT) levels; and the HOMA-insulin resistance (HOMA-IR). Results: In rats with pre-eclampsia, the systolic blood pressure; the concentrations of serum uric acid, creatinine, nitric oxide (NO), xanthine oxidase, myeloperoxidase, blood glucose, serum cholesterol, triglycerides, AST, and ALT; and the calculated HOMA-IR were significantly increased compared to those in the rats in the other groups. Additionally, apelin treatment significantly improved these parameters in the apelin-treated group. Conclusion: This study examined the potential mechanisms whereby apelin may act as a curative candidate to reduce hepatic injury and inhibit kidney damage and the development of metabolic disorders in an experimental model of preeclampsia.

Gestational protein restriction alters the RANKL/OPG system in the dental germ of offsprings

ObjectiveEvaluate the dentinogenesis in the offspring of rats submitted to gestational protein restriction (GPR). Design: The offspring were evaluated at the 21st day of gestation (21 dG). Assessments were made of morphological parameters and the RANKL/OPG system - bone tissue maturation markers - in the upper incisor tooth germ. Pregnant 10-week-old female Wistar rats were divided into normal protein (NP, 17% casein, n = 5) and low protein (LP, 6% casein, n = 5) diet groups. At 21 dG, the offspring maxillae were collected for histomorphometric and immunohistochemical analyses. Results: The LP group showed decreased thickness of the dentin and odontoblast cell layers on the tooth germ. GPR led to decreased OPG expression and increased RANKL expression in the incisor germ. Conclusion: The results suggested that gestational protein restriction altered odontoblast RANKL/OPG expression and decreased dentin matrix deposition and thickness in tooth development.

Maternal supplementation with citrulline or arginine during gestation impacts fetal amino acid availability in a model of intrauterine growth restriction (IUGR).

Supplementing maternal diet with citrulline or arginine during gestation was shown to enhance fetal growth in a model of IUGR induced by maternal dietary protein restriction in the rat. The aims of this study were to determine in the same model whether maternal supplementation with citrulline or arginine would increase 1) citrulline and arginine concentration in fetal circulation; 2) the expression of placental amino acid transporters, and 3) the fetal availability of essential amino acids. Pregnant rats (n=8 per group) were fed either an isocaloric control (20% protein, NP) or a low protein (LP, 4% protein) diet, either alone or supplemented with 2g/kg/d of l-citrulline (LP+CIT) or isonitrogenous Arginine (LP+ARG) in drinking water throughout gestation. Fetuses were extracted by C-section on the 21st day of gestation. The gene expression of system A (Slc38a1, Slc38a2, and Slc38a4) and L (Slc7a2, Slc7a5, Slc7a8) amino acid transporters was measured in placenta and amino acid concentrations determined in maternal and fetal plasma. Maternal LP diet decreased fetal (4.01±0.03 vs. 5.45±0.07g, p<0.0001) and placental weight (0.617±0.01 vs. 0.392±0.04g, p<0.001), by 26 and 36% respectively, compared with NP diet. Supplementation with either CIT or ARG increased fetal birth weight by≈5 or 11%, respectively (4.21±0.05 and 4.48±0.05g vs. 4.01±0.03g, p<0.05). CIT supplementation produced a 5- and 2-fold increase in fetal plasma citrulline and arginine, respectively, whereas ARG supplementation only increased fetal arginine concentration. LP diet led to lower placental SNAT 4 mRNA, and higher LAT2 and SNAT1 expression, compared with NP. SNAT4, 4hFC, LAT2 mRNA were up-regulated in LP+CIT and LP+ARG group compared with the un-supplemented LP group. Higher level of LAT1 mRNA was also observed in the LP+CIT group than in the LP group (p<0.01). SNAT2 expression was unchanged in response to CIT or ARG supplementation. Fetal amino acid concentrations were decreased by LP diet, and were not restored by CIT or ARG supplementation. The current findings confirm supplementation with citrulline or arginine enhances fetal growth in a rat model of IUGR. They further suggest that: 1) citrulline and arginine administered orally to the pregnant mother may reach fetal circulation; 2) citrulline effectively raises fetal arginine availability; and 3) although it failed to increase the concentrations of essential amino acids in fetal plasma, citrulline or arginine supplementation upregulates the gene expression of several placental amino acid transporters.

EFFECT OF IONISED (ELECTROLYSED) WATER ON THE RAT EMBRYO DEVELOPMENT

The aim of this study was to investigate the effects ionised water has on embryonic development using Wistar rat animal model. For that purpose, alkaline and acidic water was prepared with a domestic water ioniser. It was found that the concentrations of Cl–, SO42– ions increased in acidic water, while in alkaline water, Ca2+ concentration decreased and halogenated hydrocarbon concentrations exceeded permitted levels. The animals were given test alkaline and acidic water, as well as tap water as control. After three months, female rats were mated. On the 21st day of gestation, they were euthanized and subjected to Caesarean sections; the number of live and dead fetuses was recorded. The fetuses were examined for external or visceral malformations and skeletal abnormalities. The data showed that embryo death was higher in acidic and alkaline experimental groups in comparison to the control group. The fetuses in both test groups were significantly shorter than in the control group. Long bones of fetal hind and front limbs were shorter in the acidic group in comparison to the control group. Retardation of limb osteogenesis was expressed in the acidic group fetuses. Therefore, in our model, ionised water had a negative effect on the embryonic development.

Hyperlipidemia impairs uterine β-adrenergic signaling by reducing cAMP in late pregnant rats.

The aim of the present study was to reveal the effect of hyperlipidemia on β2- and β3-adrenergic signaling in late pregnant rat uterus. Hyperlipidemia was induced in female Wistar rats by feeding a high-fat high-cholesterol diet for 8 weeks before and after mating upto the 21st day of gestation. The effect of hyperlipidemia on β-adrenergic signaling was studied with the help of tension experiments, real-time PCR and cAMP ELISA in 21-day pregnant rat uterus. In tension experiments, hyperlipidemia neither altered the spontaneous contractility nor the oxytocin-induced contractions. However, it decreased the -logEC50 values of β2-adrenoceptor agonist, salbutamol and β3-adrenoceptor agonist, BRL37344. It also decreased the efficacy of adenylyl cyclase activator, forskolin. Further, there was a significant decrease in salbutamol and BRL37344-stimulated cAMP content in uterine tissues. However, there was no alteration in mRNA expressions of β2-adrenoceptor (Adrb2), β3-adrenoceptor (Adrb3) and Gs protein (Gnas) though there was a significant increase in the mRNA expression of Gi protein (Gnai). In conclusion, reduced cAMP content after beta-adrenergic receptor stimulation, which correlates with an increase in Gnai mRNA, may explain the mechanism of the impairment of uterine β-adrenergic signaling in hyperlipidemic pregnant rats. The clinical implication of the present study may relate to reduced myometrial relaxant response to β-adrenergic agonists in high fat-induced uterine dysfunction.

Effect of haloperidol on centrilobular vein and portal triad of liver in the albino rats during intrauterine life

Haloperidol is first generation antipsychotic used to treat psychosis. Its usage during pregnancy benefits psychotic mother and is indispensable for treating psychiatric emergency situations. Objectives: To evaluate the effects of haloperidol on development of centrilobular vein and portal triad of liver given to albino rats during intrauterine period. Study Design: Experimental study. Setting: PPGMI Animal House, Lahore. Period: July to September 2017. Materials &amp; Methods: Pregnant female rats were randomly divided into three groups A,B and C ,15 rats in each group. Group B &amp; C were given haloperidol in a dose of 0.4mg/kg and 0.8mg/kg body weight by intraperitoneal route whereas group A was considered as control group. Hysterotomy was done on 21st day of gestation and pups were removed. Pups of group A, B and C were designated as A1, B1 and C1. They were grossly examined for any abnormality and liver was removed after dissection. Slides were made and stained to evaluate changes in detailed histological study of centrilobular veins and portal triads. Results: Comparison of centrilobular vein and portal triad of group B1 and C1 with control A1 revealed that there is significant congestion seen in centrilobular veins of group B1 and C1 with P value ≤ 0.001 and signs of inflammation are present in experimental groups where were significant as compared to control group A1 with P value ≤ 0.001. Conclusion: Haloperidol, given during intrauterine life is responsible for initiating cell injury sequelae in the developing liver of fetal albino rats and must be given with caution if necessary.

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin.

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

The inhibiting activity of meadowsweet extract on neurocarcinogenesis induced transplacentally in rats by ethylnitrosourea.

Inhibitory activity of a decoction of meadowsweet, given postnatally, was studied in rats at risk for neurogenic and renal tumors initiated by transplacental exposure to ethylnitrosourea (ENU). Chemical analysis of ethanol and aqueous extracts of meadowsweet has shown high content of biologically active flavonoids and tannins. Pregnant rats of LIO strain were given a single i.v. injection of ENU, 75mg/kg, оn the 21st day of gestation. After weaning at 3 weeks after birth, the offspring were divided into two groups: the first was a positive control (ENU), while rats in the second group (ENU + meadowsweet) were given daily a decoction of meadowsweet as drinking water throughout their lifetime. All rats of the first group (ENU) developed multiple malignant tumors, which occurred in brain (86%), spinal cord (43%), peripheral and cranial nerves (29%) and in kidney (31%). More than one-third of CNS tumors were oligodendrogliomas. Mixed gliomas (oligoastrocytomas) occurred less frequently. All other types including astrocytomas, glioblastomas, and ependymomas were rare. All PNS tumors were neurinomas (schwannomas). The spectrum of tumors was similar in rats of the second group. Postnatal consumption of meadowsweet significantly reduced number of tumor-bearing rats (by 1.2 times), the incidence and multiplicity of CNS tumors (brain-by 2.0 and 2.1 times, respectively; spinal cord-by 3.1 and 3.0 times, respectively) and significantly increased latency period, compared to rats of the first group. No significant reduction in PNS or renal tumors was seen in rats given meadowsweet. Meadowsweet extract can be considered an effective cancer preventive agent especially as a neurocarcinogenesis inhibitor.

Features of endothelial dysfunction and morphofunctional changes of the uteroplacental complex in experimentally induced pre-eclampsia.

Pre-eclampsia is considered to be a severe complication of pregnancy. Theoretical investigation of its etiology and pathogenesis, development of strategies for its prevention and treatment are conditioned by the development of appropriate experimental models of this pathology. The study involved Wistar rat lines weighing 220-240g. Experimental pre-eclampsia was modeled by replacing drinking water consumed by pregnant female rats with 1.8% NaCl solution throughout gestation. Arterial pressure, protein concentration in urine and tissue hydration extent were measured on the 1st and 21st days of gestation. Uteroplacental blood flow, vasodilating and antithrombotic endothelial functions were also assessed. For pathomorphological and immunohistochemical investigation murine monoclonal antibodies against vascular endothelial growth factor (VEGF), polyclonal rabbit antibodies against inducible and endothelial NO-synthases were used. Replacing drinking water with 1.8% NaCl solution in female rats throughout gestation elevates arterial pressure, causes proteinuria and edema, impairs vasodilating and antithrombotic endothelial properties, and suppresses uteroplacental blood circulation. A morphological examination of the animals revealed the signs of focal duodenitis, spasms of myometrium arteries with no invasion of syncytiotrophoblast into its walls which also involved a raised VEGF and reduced eNOS expression in the endothelium of myometrial vessels, as well as cytoplasmic expression of iNOS in the cells of inflammatory infiltrate. These findings make it possible to conclude that replacing drinking water with 1.8% NaCl solution causes a number of changes typical of pre-eclampsia and, therefore, can be regarded as an experimental model of this pathologic condition.

Maternal citrulline supplementation enhances placental function and fetal growth in a rat model of IUGR: involvement of insulin-like growth factor 2 and angiogenic factors

Objective: To determine the effects of maternal citrulline supplementation on fetal growth and placental efficiency in a rat model of intrauterine growth restriction (IUGR) induced by maternal protein restriction.Methods: Pregnant Sprague–Dawley rats were randomly assigned to three groups: NP (receiving a control 20% protein diet), LP (a 4% protein diet), or LP-CIT (an LP diet along with L-citrulline, 2 g/kg/d in drinking water). On the 15th and 21st day of gestation (GD15 and GD21, respectively), dams underwent a C-section, by which fetuses and placentas were extracted. The expression of genes involved in placental growth and angiogenesis was studied by quantitative RT-PCR.Results: Maternal citrulline supplementation increased fetal weight at GD21, and fetal weight/placental weight ratio, an index of placental efficiency, from mid gestation (p < 0.001). The expression of Igf2-P0, a placenta-specific variant of insulin-like growth factor 2 (Igf2) gene, and Vegf and Flt-1, involved in angiogenic pathways, was enhanced in the LP-CIT group (versus NP, p < 0.001, p < 0.01, and p < 0.05 for Igf2-P0, Vegf, and Flt-1, respectively).Conclusions: In a model of IUGR induced by protein deprivation, citrulline enhances fetal growth, placental efficiency, and the expression of genes involved in angiogenesis. The relevance of such effect in human pregnancies complicated by IUGR warrants further study.

Influence of mefloquine administration during early pregnancy on rat embryonic development

Mefloquine (MQ) is a potent effective antimalarial drug against multiple drug-resistant Plasmodium falciparum. It has been proved that MQ can be given safely during the second and third trimesters. However, there is very limited information on the drug safety during the first trimester. The aim of the present work was to investigate the embryotoxicity and teratogenicity of MQ during critical periods of early development. Wistar rats were orally administered with a single dose of MQ (45 mg/kg bwt or 187 mg/kg bwt) on the 1st, 6th or 13th days of pregnancy. Cyclophosphamide (CPA) was chosen as a positive control. On the 21st day of gestation, standard parameters of reproductive performance and fetal examination were estimated. Malondialdehyde (MDA) level, glutathione reductase activity and glutathione (GSH) content were evaluated in placenta and liver homogenates of mothers and fetuses. The results indicated that MQ did not adversely affect the number of implantation, resorption, litter size and fetal body weight and length. Only groups treated with MQ on the 1st day of gestation exhibited significant decrease in fetal body weight. Examination of fetuses for external, visceral and skeletal changes showed minimal variations involving extension of lateral brain ventricles and renal pelvis and signs of delayed ossification. These variations were accompanied with significant elevation of MDA level and reduction of GSH content of fetal liver. Prenatal exposure to MQ at early pregnancy did not cause any embryolethal or teratogenic effect. It could slightly exacerbate minor variations.

Временная организация ритмов системы гемостаза и микроциркуляции при гестационном ДВС-синдроме на фоне фитокоррекции в эксперименте

The state of temporal organization of hemostasis system (HS) and microcirculation (MC) was studied in 72 rats of Wistar line weighted 200-250 gr. They were in 8 groups: intact rats, rats with physiologic pregnancy; with experimental gestosis; prophylactic and treatment-and-prophylactic injections of complex phytoadaptogens – phytococktails “Biorhythm-E” and “Biorhythm-RG”. The analysis of coagulation and microcirculation indices was performed on the 21-st day of gestation. The biorhythms were estimated with the help of “cosinor-analysis” programmer. The reliable ultradian biorhythms prevailed in the intact rats, among which there were rhythms (5%) with high and middle amplitude, with the period of 5-7 hours. The chronic intersystemic pathologic desynchronosis developed while the experimental gestosis. The usage of phytococktail “Biorhythm-E” was more effective while the architectonics of temporal organization impairment at the expense of the part of the reliable circadian rhythms increase while the treatment-and-prophylactic administration. The usage of complex phytoadaptogens promoted the increase of HS and MC adaptation resources, normalizing the impaired architectonics of biological rhythms.

CONTRACEPTIVE AND ABORTIFACIENT EFFECTS OF LIME VAGINAL DOUCHE IN ALBINO WISTAR RATS

ObjectiveTo study the contraceptive and abortifacient effects of lime vaginal douche and its consequent histopathologies on reproductive organs of adult female albino Wistar rats.MethodologyThirty‐five adult female Wistar rats were used and five adult males kept for mating. The animals were randomly divided into groups of five animals per cage. Group 1: concentrated lime juice, group 2: 50% concentrated lime juice group 3: concentrated lime juice and mated, group 4: 50% concentrated lime juice and mated, group 5: mated then administered concentrated lime juice, group 6: mated then administered 50% lime juice and group 7: control. The lime juice was administered intra‐vaginally for 2 weeks. Vaginal smears were taken daily to study the estrous cycle. Groups 1, 2 and 7 were sacrificed after two weeks and uterus, ovary and vagina were prepared for histology; while groups 3 to 6 were sacrificed on the 21st day of gestation.ResultsLime juice showed some contraceptive but no abortifacient effects; however the fetus were not well‐developed. There were some irregularities in the estrous cycle. In the rats administered lime juice, the uterus showed areas of inflammation and vascular congestion; the ovaries showed cortical area with lining degenerated, marked cellular degeneration, follicular degeneration, atrophy and inflammation while the vagina showed marked areas of cellular degeneration, vascular degeneration and inflammation.ConclusionLime juice vaginal douche has teratogenic effects and adverse effects on female reproductive system.

Abstract 8898: Oxygenation-induced Postnatal Remodeling of the Ductus Arteriosus

Introduction: Intimal thickening (IT) is an important remodeling for anatomical closure of the ductus arteirosus (DA). Although the immediate rise of oxygen tension at birth contracts DA smooth muscle, the role of oxygen in vascular remodeling remains unknown. Hypothesis: Raising oxygen tension promotes IT and anatomical DA closure. Methods: Tissues and vascular smooth muscle cells (SMCs) were obtained from the DA and aorta of rat fetuses on the 21st day of gestation. To examine the effect of raising oxygen tension, SMCs were cultured in a hypoxic chamber (1% O 2 , 5%CO 2 , pO 2 : 20 mmHg) for 3 days and then transferred to a normoxic chamber (21% O 2 , 5% CO 2 , pO 2 : 120 mmHg).Production of basic fibroblast growth factor (bFGF) and H 2 O 2 were measured by ELISA. The area of IT was evaluated by Elastica van Gieson stain. Immunohistochemical analysis was performed using human DA tissues from eight patients with various congenital heart diseases. Results: bFGF was highly expressed in the part of IT in human and rat neonatal DA. Oxygenation increased production of bFGF {1.6-fold (1h), 4.2-fold (6h), n=4-8, P &lt;0.001}, H 2 O 2 {1.8-fold (10 min), n=6, P &lt;0.01} and phosphorylation of ERK1/2 { 2.2-fold (15 min), n=5-9, P &lt;0.001} in rat DA SMCs, but not in aortic SMCs. Inhibition of reactive oxygen species (ROS) by apocinin or rotenone, or ERK inhibitor U0126 attenuated oxygen-induced bFGF production. Oxygenation and recombinant bFGF promoted DA SMC migration (1.8-fold, n=6, P &lt;0.001). Neutralizing antibody against bFGF, apocynin or rotenone attenuated oxygen-induced migration. In vivo study, intraperitoneal administration of anti-bFGF antibody, ROS inhibitor N -acetylcysteine or ERK1/2 inhibitor U0126 attenuated postnatal IT in full-term rat DA (0.8-fold, 0.8-fold, or 0.8-fold, respectively, n=4-10, P &lt;0.01). Furthermore, administration of bFGF promoted IT in preterm rat DA (1.4-fold n=4, P &lt;0.01). Co-administration of bFGF with a cyclooxygenase (COX) inhibitor, rather than a COX inhibitor alone, significantly enhanced IT and promoted closure of rat preterm DA. Conclusions: These results suggest that raising oxygen tension and subsequent induction of ROS induced bFGF secretion via ERK1/2, leading to postnatal anatomical losure of the DA.

402 Effect of Antenatal Corticosteroids in Activity and Expression of Secretory Phospholipase A2 and TNF Alfa in Lung of Newborn Rats

IntroductionThe sPLA2 plays an important role in the development of acute respiratory distress syndrome. It is regulated by many factors including steroids and TNFa. Antenatal corticosteroids are recommended for preventing...

The endothelial cells of ductus arteriosus have a unique gene profile to control vascular morphology

Patency of ductus arteriosus (PDA) is morbid; especially it is a severe problem in preterm infants. Hence, to investigate the mechanism of DA closure is important for pediatrics. The present study focused on endothelial cells (ECs) in the DA because ECs lining vessels have a variety of functions and play a central role in homeostasis of the circulatory system. We hypothesized that ECs of the DA had unique characteristics from other vessels and that they should be the primary target to investigate the molecular mechanisms of the DA‐specific vasoconstriction and vascular remodeling.Using fluorescence activated cell sorter, we isolated pure ECs from pooled tissues from the DA or the aorta of Wistar rat fetuses on the 21st day of gestation (e21) or 30 minutes after birth (day0). The gene profiling of those sorted cells were then analyzed by DNA microarray (GeneChip Rat Gene 1.0 ST Array, Affymetrix). We found 61 genes in e21 and 63 genes in day0 were specifically expressed in DA ECs than in aortic ECs (the data were cut off by p value&lt;0.01 or fold change &gt; 2.0). Among them, the genes related to cell adhesion and blood vessel morphogenesis development, such as Vegf‐a, Tgf‐beta, Tbx1, Fgf10 and Pitx2 were abundant in DA ECs, which indicates those genes play an important role in specification of DA morphology and function.

NADPH-d activity in rat thymus after the application of retinoid acid.

The aim of this work was to determine the localization of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d) activity as the marker for synthesis of nitric oxide synthase (NOS) in the rat thymus after the application of retinoid acid (RA) on 1st, 7th, 14th and 21st days of gestation. The given results can build the basis for understanding of the role of NOS in rat thymus. NADPH-d positive cells were represented with dark-blue color and were localized on corticomedullar junction of the thymus. These cells were of different intensity of coloring and were shaped in oval, circle or irregular forms. NADPH-d positive nerve fibers were observed in perivascular topography. They were marked more strongly in the case of control group. The result of application of RA to gravid rats was that the birth weights of newborn rats and their thymuses were smaller, but without statistically significance.

Dexamethasone and Betamethasone for Prenatal Lung Maturation: Differences in Vascular Endothelial Growth Factor Expression and Alveolarization in Rats

Background: Fetal and postnatal lung development is regulated by glucocorticoids. The use of antenatal corticosteroids is reported to produce effects on vascular endothelial growth factor (VEGF), which plays a crucial role in pulmonary development. Objectives: The purpose of this study was to compare pulmonary VEGF expression in newborn rats that were exposed to antenatal betamethasone versus dexamethasone and to evaluate its impact on the alveolarization period of rats (0–14 days of life). Methods: Betamethasone, dexamethasone or equivalent saline solution (control group) was administered to pregnant rats on 20th and 21st days of gestation. Pulmonary VEGF mRNA, VEGF protein expression, and alveolarization changes were evaluated at birth and at 14 days of life. Results: Betamethasone and dexamethasone were observed to have different actions on VEGF expression with a correlation with alveolarization on both days of study. Antenatal dexamethasone decreased VEGF expression, betamethasone tended to produce the induction of the expression of VEGF, and moreover, betamethasone did not produce a decrease in alveolarization as seen in the animals that received dexamethasone. Conclusions: Our results support the notion that betamethasone could be a better choice than dexamethasone for antenatal lung maturation.

Differential effect of neocuproine, a copper(I) chelator, on contractile activity in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus

The study was conducted to examine effects of a selective copper(I) chelator, neocuproine on the spontaneous or oxytocin-induced contractions in isolated ovariectomized non-pregnant rat, pregnant rat and pregnant human uterus. Uterus activity was evaluated in tissues obtained from bilaterally ovariectomized non-pregnant rats on the 21st day of the operation ( n = 24), pregnant rats on the 19–21st day of gestation ( n = 24) and women undergoing caesarean section at 38–42 weeks of pregnancy ( n = 15). Neocuproine (100 μM) significantly suppressed the amplitude and frequency of the spontaneous contractions in the ovariectomized non-pregnant rat uterus while this agent facilitated the frequency of the spontaneous or oxytocin-induced contractions in the pregnant rat and human uterus without altering the amplitude of these contractions. At high concentration of 200 μM, neocuproine could enhance the amplitude of the contractions in the pregnant uterus. These effects were blocked by a purinergic receptor antagonist, suramin (100 μM) and did not occur following the administration of neocuproine–copper(I) complex or copper(II) chelator cuprizone. α,β-methylene ATP increased the amplitude and frequency of contractions in the pregnant uterus, but not affected the contractions in the ovariectomized non-pregnant rat uterus, and neocuproine potentiated this facilitation effect. However, the suppressive effect of neocuproine on the ovariectomized non-pregnant rat uterus increased in the presence of α,β-methylene ATP. β-adrenoceptor blocker, propranolol or nitric oxide synthase inhibitor, l-nitroarginine did not affect the responses to neocuproine. These findings suggest that neocuproine can affect the uterus contractile activity by modulation purinergic excitatory responses and that copper(I)-sensitive mechanisms may play a role in this effect.