Lactogenesis in the rat. Changes in metabolic parameters at parturition.
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ABSTRACT:
SUBMITTER: Kuhn NJ
PROVIDER: S-EPMC1198418 | biostudies-other | 1967 Dec
REPOSITORIES: biostudies-other
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Project description:The process of parturition involves the complex interplay of factors that change the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery, using high-density DNA microarray. Of 8,740 sequences available in the array, a total of 3,782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term, including connexin 43 and 26, cyclooxygenase 2, and oxytocin receptor, as well as novel genes that have been not previously associated with parturition. Quantitative real-time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of the aquaporin water channel family, was dramatically downregulated during parturition (approximately 100-fold by microarray and approximately 50-fold by real-time PCR). The emerging profile highlights biochemical cascades occurring in a period of approximately 36 h that trigger parturition and the initiation of myometrium reverse remodeling postpartum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipid metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth.
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Project description:1. Lactogenesis was initiated in pregnant rats by ovariectomy, thereby causing progesterone withdrawal, after which the mammary tissue was analysed for contents of enzymes and metabolites concerned with the biosynthesis of lactose. 2. Lactose synthesis increased about 126-fold with little or no accompanying change in the contents of most metabolic intermediates or in the adenine nucleotide energy charge. 3. Comparison of mass-action ratios with equilibrium constants showed that phosphoglucomutase (EC 2.7.5.1), UDP-glucose pyrophosphorylase (EC 2.7.7.9) and UDP-glucose epimerase (EC 5.1.3.2.) catalysed reactions close to equilibrium. Nucleoside diphosphokinase (EC 2.7.4.6.) activity was very high and probably equilibrates the UTP-UDP and ATP-ADP couples. Lactose synthetase and hexokinase (EC 2.7.1.1) appeared to catalyse rate-limiting reactions. 4. Large increases were seen of UDP-glucose pyrophosphorylase (5-fold), lactose synthetase A protein (3.8-fold) and alpha-lactalbumin (28-fold), but not of hexokinase, phosphoglucomutase, UDP-glucose epimerase, nucleoside diphosphokinase or glucose 6-phosphate dehydrogenase (EC 1.1.1.49) activities. 5. It appeared that the increased lactose synthesis was largely accounted for by the increased lactose synthetase A protein activity and alpha-lactalbumin.
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Project description:Perinatal care is important in mammals due to its contribution to fetal growth, maternal health, and lactation. Substantial changes in host hormones, metabolism, and immunity around the parturition period may be accompanied by alterations in the gut microbiome. However, to our knowledge, changes in the gut microbiome and their contribution to the shifts in host metabolism around parturition have not been investigated in pigs. Furthermore, pigs are an ideal biomedical model for studying the interactions of the gut microbiota with host metabolism, due to the ease of controlling feeding conditions. Here we report dramatic remodeling of the gut microbiota and the potential functional capacity during the late stages of pregnancy (5 days before parturition, LP) to postpartum (within 6 h after delivery, PO) in both experimental and validated populations of sows (n = 107). The richness of bacteria in the gut of both pregnant and delivery sows significantly decreased, whilst the ?-diversity dramatically expanded. The ratio of Bacteroidetes to Firmicutes, and the relative abundance of Prevotella significantly decreased, whilst the relative abundance of the predominant genus Lactobacillus significantly increased from LP to PO state. The predicted functional capacities of the gut microbiome related to amino acid metabolism, the metabolism of cofactors and vitamins, and glycan biosynthesis were significantly decreased from LP to PO state. However, the abundance of the functional capacities associated with carbohydrate and lipid metabolism were increased. Consistent with these changes, serum metabolites enriched at the LP stage were associated with the metabolism of amino acids and vitamins. In contrast, metabolites enriched at the PO stage were related to lipid metabolism. We further identified that the richness and ?-diversity of the gut microbiota and the abundance of Lactobacillus accounted for shifts in the levels of bile acid metabolites associated with lipid metabolism. The results suggest that host-microbiota interactions during the perinatal period impact host metabolism. These benefit the lactation of sows by providing energy from lipid metabolism for milk production.
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Project description:BackgroundPsoriasis is associated with cardiovascular disease and metabolic syndrome but the effects of interleukin (IL)-17A inhibitor treatment on metabolic parameters are unknown. This study aimed to determine the effects of secukinumab on metabolic parameters based on the disease activity and treatment response in patients with psoriasis.MethodsIn this retrospective study, we included 99 patients with moderate to severe psoriasis, who received IL-17 inhibitor (secukinumab) treatment for 24 weeks between January 2016 and February 2020. The disease activity [Psoriasis Area and Severity Index (PASI)] and metabolic parameters at baseline and after 12 or 24 weeks of treatment were collected.ResultsThe PASI improved with a significant reduction of high-sensitivity C-reactive protein (hs-CRP) at weeks 12 and 24 respectively. However, body weight and body mass index were significantly increased at week 12 and 24 of treatment. Triglycerides level and atherogenic index of plasma were significantly higher in week 24 in PASI-90 non-responders. The baseline hs-CRP level and PASI-90 non-response correlated with elevated triglyceride levels.ConclusionOur results suggest that obesity and hypertriglyceridemia still existed in patients despite the improved disease activity after secukinumab treatment. Higher baseline hs-CRP level and PASI-90 non-response were predictors for elevated triglyceride levels after treatment. Therefore, patient education, regular screening of the lipid profile, and weight control are recommended during the treatment of secukinumab.
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Project description:Time to onset of stage II lactogenesis varies widely, and delayed onset of lactogenesis (OL) is common among first-time mothers in the United States. Higher body mass index, older age, and larger infant birth weight are identified risk factors for delayed OL; all are known correlates with glucose metabolism. Our objective was to prenatally assess maternal biomarkers related to metabolic health and determine the extent to which these biomarkers predict timing of OL.We enrolled a population-based sample of expectant primiparas attending a single prenatal clinic. We obtained a blood sample 1-hour post-glucose load from an antenatal oral glucose challenge test and assayed for the following biomarkers: serum insulin, glucose, adiponectin, leptin, C-reactive protein, interleukin-6, resistin, and tumor necrosis factor-?. Our outcome measure was timing of OL, based on maternal report at 3-5 days postpartum. We used linear regression to model OL hour.Twenty-six of 29 (90%) agreed to screening, 18 delivered at term and initiated breastfeeding, and 16 have complete data. Median (minimum-maximum) postpartum body mass index was 27.4 (21.8-34.7) kg/m(2), and median time to OL was 64 (10-121) hours. The model, OL = 232 - 34.9(ln[ratio insulin/glucose]) - 1.4(adiponectin), explained 56% of the variation in OL hour (p = 0.005) and was not weakened by potential confounders.Higher serum insulin secretion relative to serum glucose after a glucose challenge and higher serum adiponectin are associated with earlier onset of OL. These findings suggest that factors associated with better glucose tolerance predict earlier OL.
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Project description:The process of parturition involves the complex interplay of factors that changes the excitability and contractile activity of the uterus. We have compared the relative gene expression profile of myometrium from rats before parturition (21 days pregnant) and during delivery using high-density DNA microarray. Of 8740 sequences available in the array a total of 3782 were detected as present. From the sequences that were significantly altered, 59 genes were upregulated and 82 genes were downregulated. We were able to detect changes in genes described to have altered expression level at term including connexin 43 and 26, cyclo-oxygenase 2 and oxytocin receptor as well as novel genes that have been not previously associated with parturition. Quantitative real time PCR on selected genes further confirmed the microarray data. Here we report for the first time that aquaporin5 (AQP5), a member of aquaporin (AQP) water channel family, was dramatically downregulated during parturition (~100 fold by microarray and ~50 fold by Real Time PCR). The emerging profile highlights biochemical cascades occurring in a period of about 36 hours that triggers parturition and the initiation of myometrium reverse remodeling after partum. The microarray analysis uncovered genes that were previously suspected to play a role in parturition. This regulation involves genes from immune/inflammatory response, steroid/lipids metabolism, calcium homeostasis, cell volume regulation, cell signaling, cell division, and tissue remodeling, suggesting the presence of multiple and redundant mechanisms altered in the process of birth.
2008-09-23 | GSE12799 | GEO
Project description:1. The activity of 20alpha-hydroxy steroid dehydrogenase in rat ovarian corpora lutea increased at least 50-fold between 2 days before and 2 days after parturition, and then fell gradually during lactation. The activity of 3beta-hydroxy Delta(5)-steroid dehydrogenase decreased by 50% at parturition but remained constant at other times. 2. The 20alpha-hydroxypregn-4-en-3-one/progesterone concentration ratio in the ovary fell tenfold between 1 day before and 1 day after parturition, in contrast with the increase of the ratio for these steroids in plasma. 3. Pregnenolone was metabolized in intact cells or cell-free systems either to pregn-5-ene-3beta,20alpha-diol and then to 20alpha-hydroxypregn-4-en-3-one by 20alpha-hydroxy steroid dehydrogenase and 3beta-hydroxy Delta(5)-steroid dehydrogenase respectively, or directly to progesterone by the latter enzyme. The relative activities of these pathways appeared to reflect the relative amounts of the two enzymes and the concentrations of their respective coenzymes NADPH and NAD(+). 4. From these and other observations it was concluded that the cessation of progesterone secretion, which precedes parturition and lactogenesis at the end of pregnancy, is partly due to the redirected metabolism of pregnenolone away from progesterone and towards 20alpha-hydroxypregn-4-en-3-one as the secreted end product. This is primarily the consequence of the sharp increase in the activity of 20alpha-hydroxy steroid dehydrogenase. This mechanism is super-imposed on the already declining rate of net Delta(4)-steroid release by the ovary. 5. A relationship of these pathways to subcellular compartments of luteal cells is proposed.
| S-EPMC1178850 | biostudies-other
Project description:BackgroundThe decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process.MethodsChorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples.ResultsThe genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1? (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found.ConclusionsOur data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
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Project description:A prospective, single center, cohort study for surveillance of metabolic parameters in patients who will receive chemotherapy after surgical resection of colorectal cancer
| 2209650 | ecrin-mdr-crc
Project description:Circumferential stretch on the vein wall has been suggested as a potential etiological factor in the development of varicose veins. However, the influence of vein wall stretch on vein metabolism has not yet been explored. The aim of this study was to investigate the effect of short and prolonged mechanical stretch on vein wall metabolism.Circular segments of inferior vena cava from male Sprague-Dawley rats were exposed to normal 0.5-g (nonstretched) or high 2-g (stretched) tension for short (4 h) or prolonged (18 h) duration (five vein segments per group). Contraction response to phenylephrine (10-5 M) and KCl (96 mM) was elicited to observe the effect of circumferential stretch on vein function. The polar and organic metabolites in vein tissue were extracted using a bilayer extraction method. Aqueous and organic extracts were analyzed using nuclear magnetic resonance spectroscopy and ultra performance liquid chromatography coupled to mass spectrometry, respectively. Data acquired from both analytical platforms were analyzed using mathematical modeling.Increased concentrations of valine (p = .02) and choline (p = .03) metabolites and triglyceride moieties (p = .03) were observed in veins stretched for 18 h compared with the nonstretched/18 h group.Increased concentrations of branched chain amino acid valine and cell membrane constituent choline indicate increased muscle breakdown and increased metabolism of membrane phospholipids under stretch in an ex-vivo model. Increased intensities of triglyceride moieties in stretched vein segments for 18 h suggest that high pressure may induce an inflammatory response.This study has shown that prolonged mechanical circumferential stretch (18 h) alters the metabolic profile of rat inferior vena cava.
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