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Changes in blood parameters and coagulation-related gene expression in pregnant rats.

ABSTRACT: The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation-related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy progressed whereas prothrombin time and overall activity of vitamin-K-dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Conversely, compared with values for nonpregnant rats, activated partial thromboplastin time was prolonged before delivery and antithrombin time was significantly higher during fetal organogenesis and thereafter, indicating a mechanism to prevent the development of deep tissue thrombosis in dams. DNA microarray analysis revealed no differences in coagulation-related gene expression in the liver on gestation day 13 between pregnant and nonpregnant rats, whereas the gene expression of various fibrinogen-related factors, coagulation factors II and X, and the anticoagulation factor-related factor leuserpin 2 were increased on gestational day 19. In addition, changes similar to those reported previously in pregnant rats were confirmed. The data obtained from the present study can be used as background data for effective evaluation of reproductive toxicology in rats, and they suggest that the rat is a useful animal model for investigating the mechanisms of disorders in the blood coagulation system that can occur during late pregnancy in women.

SUBMITTER: Urasoko Y

PROVIDER: S-EPMC2696830 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Changes in blood parameters and coagulation-related gene expression in pregnant rats.

Urasoko Yoshinaka Y He Xi Jun XJ Ebata Tomonori T Kinoshita Yuichi Y Kobayashi Junichi J Mochizuki Masahiro M Ikeya Masamichi M

Journal of the American Association for Laboratory Animal Science : JAALAS 20090501 3

The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation-related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy progressed whereas prothrombin time and overall activity of vitamin-K-dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Conve ...[more]

PMID: 19476716

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Project description:Chlorpyrifos (CPF) is a widely used organophosphorus insecticide (OP) and putative developmental neurotoxicant in humans. The acute toxicity of CPF is elicited by acetylcholinesterase (AChE) inhibition. We characterized dose-related (0.1, 0.5, 1 and 2mg/kg) gene expression profiles and changes in cell signaling pathways 24h following acute CPF exposure in 7-day-old rats. Microarray experiments indicated that approximately 9% of the 44,000 genes were differentially expressed following either one of the four CPF dosages studied (546, 505, 522, and 3,066 genes with 0.1, 0.5, 1.0 and 2.0mg/kg CPF). Genes were grouped according to dose-related expression patterns using K-means clustering while gene networks and canonical pathways were evaluated using Ingenuity Pathway Analysis®. Twenty clusters were identified and differential expression of selected genes was verified by RT-PCR. The four largest clusters (each containing from 276 to 905 genes) constituted over 50% of all differentially expressed genes and exhibited up-regulation following exposure to the highest dosage (2mg/kg CPF). The total number of gene networks affected by CPF also rose sharply with the highest dosage of CPF (18, 16, 18 and 50 with 0.1, 0.5, 1 and 2mg/kg CPF). Forebrain cholinesterase (ChE) activity was significantly reduced (26%) only in the highest dosage group. Based on magnitude of dose-related changes in differentially expressed genes, relative numbers of gene clusters and signaling networks affected, and forebrain ChE inhibition only at 2mg/kg CPF, we focused subsequent analyses on this treatment group. Six canonical pathways were identified that were significantly affected by 2mg/kg CPF (MAPK, oxidative stress, NFΚB, mitochondrial dysfunction, arylhydrocarbon receptor and adrenergic receptor signaling). Evaluation of different cellular functions of the differentially expressed genes suggested changes related to olfactory receptors, cell adhesion/migration, synapse/synaptic transmission and transcription/translation. Nine genes were differentially affected in all four CPF dosing groups. We conclude that the most robust, consistent changes in differential gene expression in neonatal forebrain across a range of acute CPF dosages occurred at an exposure level associated with the classical marker of OP toxicity, AChE inhibition. Disruption of multiple cellular pathways, in particular cell adhesion, may contribute to the developmental neurotoxicity potential of this pesticide.

Project description:BackgroundPregnancy has major effects that make hematology parameters outside of normal reference ranges. Therefore, we conducted this study to establish reference intervals for Vietnamese pregnant women.MethodsFrom June 2023 to Augst 2023, blood samples from 879 eligible pregnant women were run on DxH 900 hematology analyzer and ACL TOP 550 coagulation analyzer. The tested parameters are prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), white blood cell (WBC) and its differentials (neutrophils, lymphocytes, monocytes, eosinophils and basophils), red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), RBC distribution width (RDW), RBC distribution width standard deviation (RDW-SD), platelet count (PLT), mean platelet volume (MPV). A non-parametric method was used to establish the 2.5th and 97.5th percentile reference intervals.ResultsPT, APTT decrease but fibrinogen increases during pregnancy. Physiological adaptations of pregnancy result in a decrease in RBC count, but an increase in WBC count and no changes in platelet count. The reference intervals for PT (seconds), APTT (seconds), fibrinogen (mg/dL), in the first trimester were 10.30-12.88, 25.40-35.46, 280.28-559.00, in the second trimester were 9.80-11.66, 24.05-33.23, 347.75-593.35, in the third trimester were 9.60-11.40, 23.40-31.80, 330.28-628.56, respectively. The reference intervals for main hematology parameters which are WBC (× 109/L), RBC (× 1012/L), HGB (g/dL), HCT (%), PLT (× 109/L) in the first trimester were 6.33-15.24, 3.73-5.32, 10.33-13.95, 32.22-42.29, 169.66-413.88, in the second trimester were 6.99-15.55, 3.33-4.98, 9.71-13.17, 30.26-40.07, 172.34-372.19, in the third trimester were 6.22-14.14, 3.54-4.98, 9.80-13.97, 31.11-42.70, 151.30-417.14, respectively.ConclusionsMost established referenced intervals from each trimester differ from other trimesters. These trimester-specific reference ranges for Vietnamese pregnant women will aid clinicians in entepreting parameters and help other laboratories adopt these ranges after validating.Trial registrationThis study is registered at www.Clinicaltrialsgov as NCT05929326.

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Changes in blood parameters and coagulation-related gene expression in pregnant rats.

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Changes in blood parameters and coagulation-related gene expression in pregnant rats.

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