Effect of over-conditioning on the hepatic global gene expression pattern of dairy cows at the end of pregnancy
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ABSTRACT:
PROVIDER: PRJNA673411 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12952874.fastq.gz | Fastqsanger.gz | |||
| SRR12952875.fastq.gz | Fastqsanger.gz | |||
| SRR12952876.fastq.gz | Fastqsanger.gz | |||
| SRR12952877.fastq.gz | Fastqsanger.gz | |||
| SRR12952878.fastq.gz | Fastqsanger.gz |
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Project description:Over-conditioning is a risk factor for upregulated pre- and postpartum fat mobilization. Therefore, we hypothesized that over-conditioning at the end of pregnancy leads to the accumulation of lipids in the liver and modifications of the hepatic gene expression pattern. The aim of this study was to evaluate the effect of over- versus normal-conditioning on the hepatic transcriptomic profile of dairy cows at the end of pregnancy. Ten dry multiparous Holstein cows were euthanized two weeks before expected calving. Body condition score (BCS) and backfat thickness (BFT) were evaluated, and blood samples for nonesterified fatty acids (NEFA) were taken before euthanasia. After euthanasia, liver biopsy samples were collected for further assessment of total lipids and RNA sequencing. Five cows were classified as normal-conditioned (BCS = 2.5–3.5) and five as over-conditioned (BCS = 3.75–5). Regression models confirmed that normal-conditioned cows had lower BCS [3.17 ± 0.10 (least square mean ± SE)], BFT (1.29 ± 0.29 cm), and serum NEFA (0.16 ± 0.04 mmol/L) in comparison to over-conditioned cows (4.35 ± 0.21, 3.14 ± 0.43 cm, and 0.38 ± 0.07 mmol/L for BCS, BFT, and NEFA, respectively). Total liver lipid percentage tended to be lower in normal- than over-conditioned cows (4.63 ± 0.40% and 6.06 ± 0.44%, respectively). In comparison to the mean liver lipid percentage of the normal and over conditioned cows, one over-conditioned cow had a relatively low (5.21%) and one normal-conditioned cow had a relatively high (6.07%) liver lipid percentage. Differentially expressed genes (DEGs) analysis (edgeR quasi-likelihood method) showed that normal-conditioned presented two upregulated and five downregulated genes in comparison to over-conditioned cows. Linear discriminant analysis effects size revealed 23 DEG between normal- versus over-conditioned cows. Notably, the liver of normal-conditioned cows had upregulated genes associated with liver functionality (albumin, selenoprotein P, and insulin-like growth factor binding protein 1 and 2). On the other hand, over-conditioned cows had upregulated genes associated with the acute phase response (complement C3, hemopexin, and lipopolysaccharide-binding protein). High basal lipolysis in over-conditioned cows at the end of pregnancy increases liver lipid content and alters the hepatic gene expression pattern to a pro-inflammatory state.
2020-10-31 | GSE160502 | GEO
Project description:Pregnancy induces changes in the transcriptome of the bovine endometrium from 15 days after insemination. However, pregnancy is less likely to occur if cows had a postpartum bacterial infection of the uterus. We hypothesized that uterine bacterial infection alters the endometrial transcriptomic signature of pregnancy. To examine the endometrial transcriptomic signature of pregnancy, cows were inseminated 130 days after intrauterine infusion of pathogenic bacteria and endometrium was collected 16 days later for RNA sequencing. We found 171 pregnancy regulated genes in cows 146 days after bacterial infection. When comparing our findings with three previous studies that described the endometrial transcriptomic signature of pregnancy in healthy cows, 24 genes were consistently differentially expressed in pregnancy, including MX1, MX2 and STAT1. However, 12 pregnancy regulated genes were only found in the endometrium of healthy cows, including ISG15 and TRANK1. Furthermore, 28 pregnancy regulated genes were only found in the endometrium of cows following bacterial infection and these were associated with altered iNOS, TLR, and IL-7 canonical signaling pathways. Although 94 predicted upstream regulators were conserved amongst the studies, 14 were found only in the endometrium of pregnant healthy cows, and 5 were found only in cows following bacterial infection, including AIRE, NFKBIA, and DUSP1. In conclusion, there were both consistent and discordant features of the endometrial transcriptomic signature of pregnancy 146 days after intrauterine bacterial infusion. These findings imply that there is an essential transcriptomic signature of pregnancy, but that infection induces long term changes in the endometrium that affect the transcriptomic response to pregnancy.
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Project description:The objective of this research was to identify a set of genes whose transcript abundance is predictive of a cow’s ability to become pregnant following artificial insemination (AI). Endometrial epithelial cells from the uterine body were collected for RNA sequencing using the cytobrush method from 193 first-service Holstein cows at estrus prior to AI (day 0). A group of 253 first-service cows not used for cytobrush collection were controls. There was no effect of cytobrush collection on pregnancy outcomes at day 30 or 70, or on pregnancy loss between day 30 and 70. There were 2 upregulated and 214 downregulated genes (FDR < 0.05, absolute fold change > 2-fold) for cows pregnant at day 30 versus those that were not pregnant. Functional terms overrepresented in the downregulated genes included those related to immune and inflammatory responses. Machine learning for fertility biomarkers with the R package BORUTA resulted in identification of 57 biomarkers that predicted pregnancy outcome at day 30 with an average accuracy of 77%. Thus, machine learning can identify predictive biomarkers of pregnancy in endometrium with high accuracy. Moreover, sampling of endometrial epithelium using the cytobrush can help understand functional characteristics of the endometrium at AI without compromising cow fertility.
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Project description:Infertility in lactating dairy cows is explained partially by the metabolic state associated with high milk production. The hypothesis was that lactating and non-lactating cows would differ in endometrial and placental transcriptomes during early pregnancy (day 28 to 42) and this difference would explain the predisposition for lactating cows to have embryonic loss at that time. Cows were either milked or not milked after calving. Reproductive [endometrium (caruncular and intercarunclar) and placenta] and liver tissues were collected on day 28, 35, and 42 of pregnancy. The primary hypothesis was rejected because no effect of lactation on mRNA abundance within reproductive tissues was found. Large differences within liver demonstrated the utility of the model to test an effect of lactation on tissue gene expression. Major changes in gene expression in reproductive tissues across time were found. Greater activation of the transcriptome for the recruitment and activation of macrophages was found in the endometrium and placenta. Changes in glucose metabolism between day 28 and 42 included greater mRNA abundance of rate-limiting genes for gluconeogenesis in intercaruncular endometrium and evidence for the establishment of aerobic glycolysis (Warburg effect) in the placenta. Temporal changes were predicted to be controlled by CSF1, PDGFB, and JUN. Production of nitric oxide and reactive oxygen species by macrophages was a mechanism to promote angiogenesis in the endometrium. Reported differences in pregnancy development for lactating versus non-lactating cows could be explained by systemic glucose availability to the conceptus and appear to be independent of the endometrial and placental transcriptomes.
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Project description:The objective of this study was to apply a quantitative proteomic approach to investigate changes in the plasma proteome of normal and over-conditioned dairy cows during the transition period. We used an animal model with a targeted difference in body condition score (BCS) at calving. For this, multiparous Holstein cows were allocated to two groups 15 weeks before anticipated calving and were fed differently to reach either high (HBCS: 7.2 NEL MJ/kg dry matter (DM) or normal BCS (NBCS: 6.8 NEL MJ/kg DM) until dry-off. Thereafter, both groups were fed identical diets. The targeted BCS difference was sustained during the dry period (7 weeks before calving) and the subsequent 12 weeks of lactation. Plasma samples (n = 5) from d -49, +7, and +21 relative to parturition were used from both groups (each n = 5) for proteome profiling in aby applying quantitative Tandem Mass Tags (TMT) approach.
2020-04-16 | PXD015958 | Pride
Project description:While dietary phosphorus (P) deprivation extending from the dry period into early lactation impairs health and productivity of cows, restricting dietary P supply during the dry period not only appears to be innocuous but rather effectively mitigates hypocalcemia during the first wk of lactation. To investigate possible negative metabolic effects of P deprivation during the dry period, the present study tested the hypothesis that restarted dietary P supply during the dry period alters the liver transcriptome of dairy cows during the periparturient period. Thirty late-pregnant multiparous Holstein-Friesian dairy cows entering their 2nd, 3rd or 4th lactation were assigned to either a dry cow ration with low (LP, 0.16% P in DM) or adequate P content (AP, 0.35% in DM) during the last 4 wk of the dry period (n = 15/group). Liver transcriptomics, which was carried out in a subset of five 2nd parity cows of each group (n = 5), and determination of selected hormones and metabolites in blood of all cows, was performed approximately one wk before calving and on d 3 postpartum. Liver tissue specimens and blood samples were obtained by a micro-invasive biopsy technique from the right 10th intercostal space and puncture of a jugular vein, respectively. 175 hepatic transcripts were expressed differentially between LP vs. AP cows in late pregnancy, and 165 transcripts differed between LP vs. AP cows in early lactation (Fold change > 1.3 and < -1.3, P < 0.05). In late pregnancy, the enriched biological processes of the up-regulated and the down-regulated transcripts were mainly related to immune processes and signal transduction (P < 0.05), respectively. In early lactation, the enriched biological processes of the up-regulated and the down-regulated transcripts were involved in mineral transport and biotransformation (P < 0.05), respectively. The plasma concentrations of the hormones and acute phase proteins (progesterone, insulin-like growth factor 1, serum amyloid alpha, haptoglobin, and 17β-estradiol) determined were not affected by P supply. These results suggest that P deprivation during the dry period moderately affects the liver transcriptome of cows in late pregnancy and early lactation, and causes no effects on important plasma hormones and acute phase proteins indicating no obvious impairment of health or metabolism of the cows.
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Project description:In dairy cows, administration of high dosages of niacin (NA) was found to cause anti-lipolytic effects, which are mediated by the NA receptor hydroxyl-carboxylic acid receptor 2 (HCAR2) in white adipose tissue (WAT), and thereby to an altered hepatic lipid metabolism. However, almost no attention has been paid to possible direct effects of NA in cattle liver, despite showing that HCAR2 is expressed also in the liver of cattle and is even more abundant than in WAT. Due to this, we hypothesized that feeding of rumen-protected NA to dairy cows influences critical metabolic and/or signaling pathways in the liver through inducing changes in the hepatic transcriptome. In order to identify these pathways, we applied genome-wide transcript profiling in liver biopsies obtained at 1 wk postpartum (p.p.) from dairy cows of a recent study (Zeitz et al., 2018) which were fed a total mixed ration without (control group) or with rumen-protected NA from 21 d before calving until 3 wk p.p. Hepatic transcript profiling revealed that a total of 487 transcripts were differentially expressed [filter criteria fold change (FC) > 1.2 or FC < -1.2 and P < 0.05] in the liver at 1 wk p.p. between cows fed NA and control cows. Substantially more transcripts were down-regulated (n = 338), while only 149 transcripts were up-regulated by NA in the liver of cows. Gene set enrichment analysis (GSEA) for the up-regulated transcripts revealed that the most enriched gene ontology (GO) biological process terms were exclusively related to immune processes, such as leukocyte differentiation, immune system process, leukocyte differentiation, activation of immune response and acute inflammatory response. In line with this, the plasma concentration of the acute phase protein haptoglobin tended to be increased in dairy cows fed rumen-protected NA compared to control cows (P < 0.1). GSEA of the down-regulated transcripts showed that the most enriched biological process terms were related to metabolic processes, such as cellular metabolic process, small molecule metabolic process, lipid catabolic process, organic cyclic compound metabolic process, small molecule biosynthetic process and cellular lipid catabolic process. In conclusion, hepatic transcriptome analysis shows that rumen-protected NA induces genes which are involved mainly in immune processes including acute phase response and stress response in dairy cows at wk 1 p.p. These findings indicate that supplementation of rumen-protected NA to dairy cows in the periparturient period may induce or amplify the systemic inflammation-like condition which is typically observed in the liver of high-yielding dairy cows in the p.p. period.
2018-06-21 | GSE116058 | GEO