scholarly journals Impacts of maternal nutrition on uterine and placental vascularity and mRNA expression of angiogenic factors during the establishment of pregnancy in beef heifers1

2017 ◽  
Vol 1 (2) ◽  
pp. 160-167 ◽  
Author(s):  
K. J. McLean ◽  
M. S. Crouse ◽  
M. R. Crosswhite ◽  
N. Negrin Pereira ◽  
C. R. Dahlen ◽  
...  

Abstract We hypothesized that maternal nutrient restriction starting at the time of breeding would influence placental vascular development and gene expression of angiogenic factors during the first 50 d of gestation in beef heifers. Commercial Angus crossbred heifers (n = 49) were maintained on a total mixed ration and supplemented with dried distillers grains with solubles. All heifers were subject to 5-d CO-Synch + CIDR estrous synchronization protocol, AI to a single Angus sire, and randomly assigned to dietary treatments. One half were assigned to control diet (CON) targeted to gain 0.45 kg/d and the remaining half were assigned to restricted diet (RES), which received 60% of CON. Heifers were subjected to ovariohysterectomy on d 16, 34, or 50 of gestation. Utero-placental tissues were obtained from the uterine horns ipsilateral and contralateral to the corpus luteum and separated into maternal caruncle (CAR); maternal endometrium, inter-caruncle (ICAR), and fetal membranes (FM). After collection, all tissues were snap frozen and stored at –80°C. There were no treatment × stage of gestation interactions (P >0.13) on the mRNA expression of vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS). Heifers on CON treatment had greater (P = 0.03) expression of VEGF compared with RES heifers in NP-ICAR. On d 50 expression of eNOS was increased (P = 0.05) compared with d 16 in P-CAR. Expression of eNOS mRNA was decreased (P = 0.04) on d 16 compared with d 34 and 50 in CON heifer. Gene expression of eNOS was increased (P < 0.001) in the pregnant uterine horn compared with the NP uterine horn on d 34 and 50. Expression of eNOS was also increased (P < 0.003) on d 34 and 50 in the pregnant uterine horn compared with FM. There was a maternal nutritional plane × stage of gestation interaction (P = 0.01) on the vascular ratio (vascular volume/tissue volume) in maternal tissues. The RES heifers had a greater vascular ratio on d 16 compared with d 34 and 50; whereas, CON heifers had a greater vascular ratio on d 34 compared with d 16 and 50. In the NP uterine horn, there was also an increase (P = 0.02) in vascular volume of FM from CON heifers compared with FM from RES heifers. We conclude that maternal nutrient restriction did alter both vascularity and mRNA expression of angiogenic factor in utero-placental tissues during the establishment of pregnancy in first parity beef heifers.

2006 ◽  
Vol 76 (3) ◽  
pp. 138-146
Author(s):  
Yukari Egashira ◽  
Makiko Sato ◽  
Mayuki Sato ◽  
Ryoko Sugawara ◽  
Atsushi Tanabe ◽  
...  

Hepatic α-amino-β-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis from tryptophan. The aim of this study was to evaluate the ACMSD mRNA expression after pyrazinamide or peroxisome proliferators ingestion. When rats were fed a control (pyrazinamide- and clofibrate-free) diet, 1% pyrazinamide- or 0.24% clofibrate-containing diets for 8 days, hepatic ACMSD activity and mRNA in rats consuming the clofibrate-containing diet was strongly suppressed, as compared with those fed the control and pyrazinamide diet. Pyrazinamide suppressed liver and kidney ACMSD activities, but did not affect ACMSD mRNA. Blood NAD was increased in the clofibrate and pyrazinamide groups. Shifting from the control diet to a clofibrate diet suppressed ACMSD mRNA strongly at day 1 and continued through day 4. However ACMSD activity decreased gradually. In rats fed with several kinds of peroxisome-proliferator-containing diets such as phthalate ester, bezafibrate, Wy-14,643, 2-(-4-chlorophenoxy) propionic acid, or dehydroisoandrosterone for 8 days, hepatic ACMSD mRNA was drastically decreased by all the peroxisome proliferators. These results suggest that the transcription level of hepatic ACMSD is modulated by peroxisome proliferators, and the fluctuation of the hepatic ACMSD mRNA expression was followed by that of the ACMSD activity. However, pyrazinamide does not affect the transcription level of hepatic ACMSD.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Ramon Diaz Trelles ◽  
Maria Cecilia Scimia ◽  
Pilar Ruiz Lozano ◽  
Mark Mercola

Cardiac microvasculature density is critical for a correct cardiac function under normal and stress conditions. We found that the transcription factor RBPJ, downstream of the Notch signalling, can regulate angiogenic factors gene expression by repression (normal homeostasis) or activation (stress) and also by modulating the hypoxia induced angiogenic response. Accordingly, in normal conditions cardiomyocyte specific RBPJ KO adult mice hearts show a denser microvasculature. Isolated mouse adult cardiomyocytes show increased gene expression and promoter hyperacetylation and hypermethylation of angiogenic factors and Notch target genes (like HES1). Stress induced by myocardial infarction (MI) or cardiac overload (TAC) activate an angiogenic response to compensate the increased oxygen demand. Notch pathway is activated and RBPJ accumulated in the nucleus after MI and TAC. After TAC, deletion of RBPJ did not block hypertrophy induction, but prevented the increase in angiogenic factor production and microvessel density that normally occurs in response to increased workload. Remarkably, the KO preserved cardiac function and reduced cell death and fibrosis after myocardial infarction. Thus, RBPJ acts in cardiomyocytes as a master factor orchestrating homeostatic and disease-induced angiogenesis, and modulating RBPJ protects against ischemic injury.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 307-307
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
Kendall C Swanson ◽  
...  

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on fetal liver and muscle development, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver and skeletal muscle samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver was analyzed for general tissue morphology, and fetal skeletal muscles were analyzed for lipid accumulation. mRNA expression of growth and metabolic factors were quantified in liver and muscle tissues. Hepatocellular vacuolation was increased in RES-CON and RES-RES compared with CON-CON and CON-RES (P < 0.01). In semitendinosus and triceps brachii, intramyocellular lipid content increased 19% and 15%, respectively, in RES-CON and RES-RES compared with CON-CON and CON-RES (P£0.02) and in longissimus dorsi, lipid content was decreased 7% in CON-RES and RES-RES compared with CON-CON and RES-CON (P=0.01). In liver, insulin-like growth factor binding protein-1, glycogen synthase 2, and pyruvate dehydrogenase kinase 1 expression increased 1.92-fold, 1.45-fold, and 1.47-fold, respectively (P£0.03) in CON-RES and RES-RES compared with RES-CON and CON-CON. In LD, IGF1-R expression increased 3.19-fold in CON-RES and RES-RES compared with RES-CON and CON-CON (P = 0.05). These results demonstrate that maternal nutrient restriction followed by re-alimentation restores liver and muscle gene expression of growth and metabolic factors while negatively impacting liver composition and muscle lipid content potentially leading to altered tissue function and metabolism later in life. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Ji Chen ◽  
Xiang Xiao ◽  
Cheng Zhang ◽  
Shuzhen Chen ◽  
Jianying Chen ◽  
...  

Microparticles (MPs) represent a novel network for intercellular communication. Our previous works found that MPs from db/db diabetic mice impaired endothelial progenitor cell function. This study investigated the role of MPs from mesenchymal stromal cells (MSCs) in regulating cerebrovascular endothelial cell (cEC) function and gene expression. Male C57BL/6 mice and green fluorescent protein (GFP)-transgenic mice were used for cEC and MSC donors, respectively. The cECs were cultured on 6-well plates and MSCs were seeded on well inserts with a 0.4 μm pore sized filter for co-culture for 3 days before various measurements. MSC conditional medium (MSC-CM) was used for producing MPs and MSC-CM deprived of MPs (MSC-CM-dMP) by centrifuge. MPs deprived of mRNAs and miRNAs (MSC-MP-dRNA) were prepared by treating with RNAse. In some experiments, cECs were incubated with normal culture medium (control), MSC-CM, MSC-CM-dMP, MSC-MPs or MSC-MP-dRNA for 3 days. After different treatments, the cECs were used for confocal microscopy analysis of GFP level, real-time PCR analysis of angiogenic gene expression and functional analyses. The levels of angiogenic factors were measured by ELISA method. Results showed: 1) GFP-MPs were appeared in cEC culture medium, and GFP was detected in cECs after co-culture with MSCs; 2) Co-culture with MSCs or culture with MSC-CM significantly upregulated mRNA expression of VEGFR2 and CXCR4 in cECs and increased the angiogenic factors (VEGF and SDF-1) in culture supernatant; 3) Co-culture with MSCs or culture with MSC-CM increased cEC function (migration: 68.6 ± 3.2, 66.8 ± 2.6 and 48.8 ± 2.6 tubes/field for MSC, MSC-CM and control, respectively; tube formation: 52.8 ± 2.6, 48.8 ± 2.0 and 32.6 ± 1.2 tubes/field for MSC, MSC-CM and control, respectively; n=5/group, P <0.05 or 0.01, vs. control); 4) Whereas, incubation with MSC-CM-dMP or MSC-MP-dRNA aborted the effect on mRNA expression, and reduced the functional effects by about 50%. In conclusion, MPs mediate angiogenic effect of MSCs on cECs via RNA and/or protein deliveries, which represent a novel mechanism of cell communication, providing a potential therapeutic target for endothelial dysfunction and cerebrovascular diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wellison J. S. Diniz ◽  
Matthew S. Crouse ◽  
Robert A. Cushman ◽  
Kyle J. McLean ◽  
Joel S. Caton ◽  
...  

AbstractThe molecular basis underlying fetal programming in response to maternal nutrition remains unclear. Herein, we investigated the regulatory relationships between genes in fetal cerebrum, liver, and muscle tissues to shed light on the putative mechanisms that underlie the effects of early maternal nutrient restriction on bovine developmental programming. To this end, cerebrum, liver, and muscle gene expression were measured with RNA-Seq in 14 fetuses collected on day 50 of gestation from dams fed a diet initiated at breeding to either achieve 60% (RES, n = 7) or 100% (CON, n = 7) of energy requirements. To build a tissue-to-tissue gene network, we prioritized tissue-specific genes, transcription factors, and differentially expressed genes. Furthermore, we built condition-specific networks to identify differentially co-expressed or connected genes. Nutrient restriction led to differential tissue regulation between the treatments. Myogenic factors differentially regulated by ZBTB33 and ZNF131 may negatively affect myogenesis. Additionally, nutrient-sensing pathways, such as mTOR and PI3K/Akt, were affected by gene expression changes in response to nutrient restriction. By unveiling the network properties, we identified major regulators driving gene expression. However, further research is still needed to determine the impact of early maternal nutrition and strategic supplementation on pre- and post-natal performance.


2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 217-217
Author(s):  
Dale A. Redmer ◽  
Raymond P. Aitken ◽  
John S. Milne ◽  
Mary Lynn Johnson ◽  
David B. Carlson ◽  
...  

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 98-98
Author(s):  
Brandon I Smith ◽  
Manuel A Vásquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Kendall C Swanson ◽  
Anna T Grazul-Bilska ◽  
...  

Abstract The duration and timing of inadequate maternal nutrition can have detrimental effects on metabolism and organogenesis in the offspring. Re-alimentation, a common management practice that involves feeding full nutrient requirements following a period of nutrient restriction, may reduce the negative impacts of maternal nutrient restriction. To determine the effects of maternal nutrient restriction and re-alimentation on offspring growth,48 primiparous ewes, confirmed pregnant with singletons, were fed a control diet consisting of100% NRC requirements (CON) starting on day25 of gestation. On day50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or60% NRC requirements (RES). On day90 of gestation, a portion of ewes were euthanized (n = 7 per treatment) and fetal samples and weights were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternative diet (CON-RES, RES-CON; n = 7/treatment). On day130 of gestation, all remaining ewes were euthanized. All fetal BW, liver, longissimus muscle, semitendinosus, and triceps brachii weights were determined for each day of gestation. Fetal BW’s were not different between treatment groups (P = 0.29; P = 0.83). Fetal liver weights decreased12.89% in RES-RES compared with CON-CON at day130 (P = 0.049), but were not different at day90 (P = 0.69). There was a tendency for decreased semitendinosus weight in RES group compared with CON at day90 (P = 0.055). Liver lipid droplet accumulation was analyzed for day90 and130 using histochemistry and an effect of maternal nutrition was not observed (P = 0.562). In summary, maternal nutrient restriction reduces offspring muscle and liver growth. To gain insight into the effects of maternal nutrient restriction and re-alimentation on liver development and metabolism, analysis of liver morphology, gene expression, and global metabolomics are needed. Supported by USDA-AFRI grant2016-67016-24884


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 304-305
Author(s):  
Dana Reid ◽  
Lauren Ellison ◽  
Kalisha Yankey ◽  
Caleb O Lemley ◽  
Derris Burnett

Abstract Proper maternal nutrition during gestation is an important determinant of fetal and long-term developmental programming. Transcriptional networks involved in economically important processes such as adipogenesis and overall growth of the offspring are particularly susceptible to developmental perturbations and programming. Low quality forages or insufficient maternal nutrient supplementation during gestation are scenarios that can negatively affect fetal growth and development by altering the regulation of these networks. Therefore, the purpose of this study was to determine the effect of maternal nutrient restriction during mid-to-late gestation on mRNA expression of genes involved in growth and adipogenesis in fetal back fat (BF), and perirenal adipose tissue (PR). A total of six multiparous, commercial cows were equally divided into one of two dietary treatments: Control (CON; fed 100% of NRC recommendations) vs. Restricted Feed (RES; fed 60% of NRC recommendations) from 140 to 240 days of gestation. The animals were euthanized on day 240 of gestation for fetal tissue collection and qPCR analysis using TaqMan® gene expression assays. Relative mRNA quantification was determined using the Delta-Delta Ct method. Differences between Least Square Means were compared using the PDIFF option of the MIXED procedure of SAS (9.4). PPARg expression was increased (P = 0.009) in BF tissue in the RES group compared to the CON group. IGF-1 expression tended to increase (P = 0.076), and IGF-1R expression tended to decrease (P = 0.055) in fetal BF. In PR tissue, CEBPA and IGF-1 expression decreased (P ≤ 0.043) in RES compared to CON. These findings suggest that as a result of a compromised fetal environment, the PR and BF depots are differentially regulated in a manner that may persist into postnatal life and warrants further investigation.


2020 ◽  
Vol 20 (18) ◽  
pp. 2274-2284
Author(s):  
Faroogh Marofi ◽  
Jalal Choupani ◽  
Saeed Solali ◽  
Ghasem Vahedi ◽  
Ali Hassanzadeh ◽  
...  

Objective: Zoledronic Acid (ZA) is one of the common treatment choices used in various boneassociated conditions. Also, many studies have investigated the effect of ZA on Osteoblastic-Differentiation (OSD) of Mesenchymal Stem Cells (MSCs), but its clear molecular mechanism(s) has remained to be understood. It seems that the methylation of the promoter region of key genes might be an important factor involved in the regulation of genes responsible for OSD. The present study aimed to evaluate the changes in the mRNA expression and promoter methylation of central Transcription Factors (TFs) during OSD of MSCs under treatment with ZA. Materials and Methods: MSCs were induced to be differentiated into the osteoblastic cell lineage using routine protocols. MSCs received ZA during OSD and then the methylation and mRNA expression levels of target genes were measured by Methylation Specific-quantitative Polymerase Chain Reaction (MS-qPCR) and real.time PCR, respectively. The osteoblastic differentiation was confirmed by Alizarin Red Staining and the related markers to this stage. Results: Gene expression and promoter methylation level for DLX3, FRA1, ATF4, MSX2, C/EBPζ, and C/EBPa were up or down-regulated in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21. ATF4, DLX3, and FRA1 genes were significantly up-regulated during the OSD processes, while the result for MSX2, C/EBPζ, and C/EBPa was reverse. On the other hand, ATF4 and DLX3 methylation levels gradually reduced in both ZA-treated and untreated cells during the osteodifferentiation process on days 0 to 21, while the pattern was increasing for MSX2 and C/EBPa. The methylation pattern of C/EBPζ was upward in untreated groups while it had a downward pattern in ZA-treated groups at the same scheduled time. The result for FRA1 was not significant in both groups at the same scheduled time (days 0-21). Conclusion: The results indicated that promoter-hypomethylation of ATF4, DLX3, and FRA1 genes might be one of the mechanism(s) controlling their gene expression. Moreover, we found that promoter-hypermethylation led to the down-regulation of MSX2, C/EBP-ζ and C/EBP-α. The results implicate that ATF4, DLX3 and FRA1 may act as inducers of OSD while MSX2, C/EBP-ζ and C/EBP-α could act as the inhibitor ones. We also determined that promoter-methylation is an important process in the regulation of OSD. However, yet there was no significant difference in the promoter-methylation level of selected TFs in ZA-treated and control cells, a methylation- independent pathway might be involved in the regulation of target genes during OSD of MSCs.


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