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Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits.

ABSTRACT: Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.

SUBMITTER: Schindler M

PROVIDER: S-EPMC7037143 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits.

Schindler Maria M Pendzialek Sophia Mareike SM Grybel Katarzyna K Seeling Tom T Navarrete Santos Anne A

International journal of molecular sciences 20200130 3

Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan tr ...[more]

PMID: 32019238

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Project description:BackgroundProliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy.MethodsA total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS).ResultsThe distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively.ConclusionsThis study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy.

Project description:BackgroundThe bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences.MethodsIn this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments.ResultsWe found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis.ConclusionThis study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis.

Project description:Whether osteoarthritis (OA) is a systemic metabolic disorder remains controversial. The aim of this study was to investigate the metabolic characteristics between plasma and knee joint fluid (JF) of patients with advanced OA using a differential correlation metabolic (DCM) networks approach. Plasma and JF were collected during the joint replacement surgery of patients with knee OA. The biological samples were pretreated with standard procedures for metabolite analysis. The metabolic profiling was conducted by means of liquid mass spectrometry coupled with a AbsoluteIDQ kit. A DCM network approach was adopted for analyzing the metabolomics data between the plasma and JF. The variation in the correlation of the pairwise metabolites was quantified across the plasma and JF samples, and networks analysis was used to characterize the difference in the correlations of the metabolites from the two sample types. Core metabolites that played an important role in the DCM networks were identified via topological analysis. One hundred advanced OA patients (50 men and 50 women) were included in this study, with an average age of 65.0 ± 7.6 years (65.6 ± 7.1 years for females and 64.4 ± 8.1 years for males) and a mean BMI of 32.6 ± 5.8 kg/m2 (33.4 ± 6.3 kg/m2 for females and 31.7 ± 5.3 kg/m2 for males). Age and BMI matched between the male and female groups. One hundred and forty-five nodes, 567 edges, and 131 nodes, 407 edges were found in the DCM networks (p < 0.05) of the female and male groups, respectively. Six metabolites in the female group and 5 metabolites in the male group were identified as key nodes in the network. There was a significant difference in the differential correlation metabolism networks of plasma and JF that may be related to local joint metabolism. Focusing on these key metabolites may help uncover the pathogenesis of knee OA. In addition, the differential metabolic correlation between plasma and JF mostly overlapped, indicating that these common correlations of pairwise metabolites may be a reflection of systemic characteristics of JF and that most significant correlation variations were just a result of "housekeeping" biological reactions.

Dataset Information

Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits.

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Metabolic Profiling in Blastocoel Fluid and Blood Plasma of Diabetic Rabbits.

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