scholarly journals Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau

2012 ◽  
Vol 44 (16) ◽  
pp. 799-810 ◽  
Author(s):  
N. Forde ◽  
G. B. Duffy ◽  
P. A. McGettigan ◽  
J. A. Browne ◽  
J. P. Mehta ◽  
...  

The aims of this study were to 1) identify the earliest transcriptional response of the bovine endometrium to the presence of the conceptus (using RNAseq), 2) investigate if these genes are regulated by interferon tau (IFNT) in vivo, and 3) determine if they are predictive of the pregnancy status of postpartum dairy cows. RNAseq identified 459 differentially expressed genes (DEGs) between pregnant and cyclic endometria on day 16. Quantitative real-time PCR analysis of selected genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and DDX58 expression increased in pregnant compared with cyclic endometria on day 16 and were directly upregulated by intrauterine infusion of IFNT in vivo for 2 h ( P < 0.05). On day 13 following estrous endometrial expression of nine genes increased [ ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven genes decreased ( SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, MGC128929, and WBSCR17; P < 0.05) in pregnant compared with cyclic heifers. Of these DEGs, significant differences in expression between pregnant and cyclic endometria were maintained on day 16 for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, and ZSWIM4 ( P < 0.05) both their expression was not directly regulated by IFNT in vivo. Analysis of the expression of selected interferon-stimulated genes in blood samples from postpartum dairy cows revealed a significant increase ( P < 0.05) in expression of ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared with cyclic controls. In conclusion, RNAseq identified a number of novel pregnancy-associated genes in the endometrium of cattle during early pregnancy that are not regulated by IFNT in vivo. In addition, a number of genes that are directly regulated by short term exposure to IFNT in vivo are differentially expressed on day 18 following estrus detection in the blood of postpartum dairy cows depending on their pregnancy status.

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Alicja Kowalczyk ◽  
Ewa Czerniawska-Piątkowska ◽  
Marcjanna Wrzecińska

Several decades of improving dairy cattle towards unilateral utilization of dairy cattle led to enormous progress in the field of milk yield; however, it resulted in a number of unfavorable features, such as reproductive disorders, increased calf mortality, and reduced health. Most cases of embryo loss and/or lost pregnancies occur during the first four to five weeks of gestation; accurate detection for pregnancy during this period is likely to contribute to an improvement in gestation rates. A specific protein, interferon-tau (IFNT), stimulates interferon-stimulated genes (ISGs), and their expression increases during gestation within 21 days after insemination. In bovines, the early conceptus undergoes a phase of rapid growth and elongation before implantation, the latter occurring 2–3 weeks after fertilization. IFNT acts mainly in the endometrium of the luminal epithelium. It is a new type I interferon that regulates several genes encoding uterine-derived factors. They are crucial in the processes of preparing the uterus for placenta attachment, modifying the uterine immune system, and regulating early fetal development. Because IFNT is expressed and induces ISGs in the endometrium during pregnancy recognition, it was reasoned that surrogate markers for pregnancy or IFNT might be present in the blood and provide an indicator of pregnancy status in cattle.


2010 ◽  
Vol 93 (5) ◽  
pp. 1934-1943 ◽  
Author(s):  
C.A. Piccinato ◽  
R. Sartori ◽  
S. Sangsritavong ◽  
A.H. Souza ◽  
R.R Grummer ◽  
...  

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 884 ◽  
Author(s):  
Dionysios V. Chartoumpekis ◽  
Panos G. Ziros ◽  
Ilias Georgakopoulos-Soares ◽  
Adam A. T. Smith ◽  
Ana Claudia Marques ◽  
...  

Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory–autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves’ disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves’ disease) and PTC.


2017 ◽  
Vol 49 (4) ◽  
pp. 230-237 ◽  
Author(s):  
Rafael U. Heiss ◽  
Fabian B. Fahlbusch ◽  
Johannes Jacobi ◽  
Christoph Daniel ◽  
Arif B. Ekici ◽  
...  

Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. Previous studies indicated an impairment of ischemia-induced angiogenesis in skeletal muscle of rats with CKD. We performed a systematic comparison of early gene expression in response to ischemia in rats with or without CKD to identify potential molecular mechanisms underlying impaired angiogenesis in CKD. CKD was induced in male rats by 5/6 nephrectomy (SNX); control rats were sham operated (sham). Eight weeks later, ischemia of the right limb was induced by ligation and resection of the femoral artery. Rats were killed 24 h after the onset of ischemia, and RNA was extracted from the musculus soleus of the ischemic and the nonischemic hindlimb. To identify differentially expressed transcripts, we analyzed RNA with Affymetrix GeneChip Rat Genome 230 2.0 Arrays. RT-PCR analysis of selected genes was performed to validate observed changes. Hindlimb ischemia upregulated 239 genes in CKD and 299 genes in control rats (66% overlap), whereas only a few genes were downregulated (14 in CKD and 34 in controls) compared with the nonischemic limb of the same animals. Comparison between the ischemic limbs of CKD and controls revealed downregulation of 65 genes in CKD; 37 of these genes were also among the ischemia-induced genes in controls. Analysis of functional groups (other than angiogenesis) pointed to genes involved in leukocyte recruitment and fatty acid metabolism. Transcript expression profiling points to a relatively small number of differentially expressed genes that may underlie the impaired postischemic angiogenesis in CKD.


Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1408-1420 ◽  
Author(s):  
Kirsten S. Eckstrum ◽  
Karen E. Weis ◽  
Nicholas G. Baur ◽  
Yoshihiro Yoshihara ◽  
Lori T. Raetzman

Abstract Endocrine-disrupting chemicals are prevalent in the environment and can impair reproductive success by affecting the hypothalamic-pituitary-gonadal axis. The developing pituitary gland is sensitive to exposure to endocrine-disrupting chemicals, such as bisphenol A (BPA), and sex-specific effects can occur. However, effects on the critical window of neonatal pituitary gland development in mice have not been explored. Therefore, this study determined baseline gene expression in male and female pituitaries and consequences of environmental exposure to 17β-estradiol (E2) and BPA on transcription of genes exhibiting sex differences during the neonatal period. Through microarray and quantitative RT-PCR analysis of pituitaries at postnatal day (PND)1, 3 genes were differentially expressed between males and females: Lhb, Fshb, and intracellular adhesion molecule-5 (Icam5). To see whether E2 and BPA exposure regulates these genes, pituitaries were cultured at PND1 with 10−8M E2 or 4.4 × 10−6M BPA. E2 decreased expression of Lhb, Fshb, and Icam5 mRNA in females but only significantly decreased expression of Icam5 in males. BPA decreased expression of Icam5 similarly to E2, but it did not affect Lhb or Fshb. Importantly, in vivo exposure to 50-μg/kg · d E2 from PND0 to PND7 decreased expression of Lhb, Fshb, and Icam5 mRNA in both males and females, whereas 50-mg/kg · d BPA exposure during the same time frame decreased expression of Icam5 in females only. Overall, we have uncovered that genes differentially expressed between the sexes can be regulated in part by hormonal and chemical signals in vivo and directly at the pituitary and can be regulated in a sex-specific manner.


2022 ◽  
Vol 2 (1) ◽  
pp. 53-72
Author(s):  
Teemu Rinttilä ◽  
Colm A. Moran ◽  
Juha Apajalahti

We first sought to evaluate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA), on rumen fermentation and the resistance of DHA to degradation and biohydrogenation by rumen microbes through ex vivo fermentation experiments. Subsequently, we sought to quantify the diet-derived DHA content of milk and the impact of AURA on microbial composition and metabolism in a pilot feeding trial with rumen-cannulated dairy cows. To achieve our aims, rumen fluid from cannulated cows was used as inoculum, and the effect of AURA inclusion on fermentation ex vivo was examined. At doses corresponding to the amount of AURA recommended for commercial production animals, only ~10% of DHA was degraded or biohydrogenated by rumen microorganisms. The results show that feeding with AURA had no effect on either total bacterial density or short-chain fatty acid production. Real-time quantitative PCR analysis of the rumen fluid samples collected during a seven-week in vivo trial revealed that microbes related to lactic acid metabolism and methanogenesis were significantly suppressed by the AURA-supplemented diet. The DHA concentration in milk increased over 25-fold with the AURA-supplemented diet and dropped by 30–40% within one week of washout. The addition of A. limacinum biomass to dairy cow diets resulted in positive effects on rumen microbial composition with no adverse effect on fermentation activity. AURA-derived DHA was stable, with only modest degradation in the rumen, and was successfully deposited in milk. This is the first study to investigate the effect of supplementing the diet of dairy cows with a protist-based biomass, namely, on important rumen fermentation parameters and on DHA deposition in milk, using a combination of ex vivo and in vivo approaches.


2010 ◽  
Vol 22 (1) ◽  
pp. 274 ◽  
Author(s):  
M. Clemente ◽  
I. Lopez-Vidriero ◽  
P. O'Gaora ◽  
J. de la Fuente ◽  
A. Gutierrez-Adan ◽  
...  

The majority of embryonic mortality in cattle occurs before maternal recognition of pregnancy at Day 16 postconception. In vitro-derived embryos exhibit a greater incidence of loss than their in vivo-derived counterparts. To better understand the causes of such embryonic loss, the aim of the current study was to compare transcript profiles of Days 7 and 13 bovine embryos derived in vitro or in vivo using the bovine Affymetrix microarray. We wanted to answer 3 questions: (1) what genes differ on Day 7 between blastocysts derived in vivo or in vitro, (2) what genes differ between Day 13 embryos derived from in vitro or in vivo embryos, and (3) what genes change between the blastocyst stage (Day 7) and the initiation of elongation (Day 13) and how are these temporal changes affected by the origin of the embryo. Day 7 bovine blastocysts were produced either in vitro by maturation, fertilization, and culture or in vivo by superovulation, AI, and nonsurgical embryo recovery. Half of the Day 7 blastocysts were snap frozen in liquid nitrogen in pools of 25 (microarray) or 10 (quantitative RT-PCR), and the other half were transferred in groups of 10 to synchronized heifers (10 recipients per group) ipsilateral to the corpus luteum and recovered on Day 13 by flushing the uterus after slaughter. Day 13 conceptuses were snap frozen individually. Three replicate pools of 25 Day 7 blastocysts and 5 Day 13 conceptuses were used for microarray analysis. Of the 24 128 probe-sets on the array, approximately 9500 genes were actively expressed in Days 7 and 13 embryos, irrespective of source. In Day 7 blastocysts, 50 genes were found to be differentially expressed (≥ 1.5-fold; P ≤ 0.05), of which 19 were up-regulated and 31 down-regulated in the in vivo compared with in vitro embryos. In Day 13 conceptuses, 288 genes were found to be differentially expressed (≥1.5-fold; P ≤ 0.05), of which 133 were up-regulated and 155 down-regulated in the in vivo compared with in vitro embryos. The comparison between Days 7 and 13 embryos revealed significant temporal changes in transcript profile, with 1806 and 909 transcripts differentially expressed in in vitro and in vivo-derived embryos, respectively. Across the 3 array comparisons between Days 7 and 13 embryos, 444 genes were consistently exclusively present in in vivo embryos, whereas 1341 were exclusively present in in vitro embryos. Array validation was done by quantitative RT-PCR analysis of fatty acid desaturase 1 (FADS1), cytochrome P450, family 51, subfamily A, polypeptide I (CYP51), and hyaluronan binding protein 2 (HABP2) genes. In conclusion, these results indicate that the origin of the blastocyst can have a significant effect on the transcript profile of the conceptus at the initiation of elongation and might be associated with the likelihood of embryo survival/loss subsequently. Further hierarchical clustering analysis and quantitative RT-PCR data will address the functional roles for certain known genes and novel candidate genes related to embryonic mortality. This work was supported by a grant (AGL2006-05616) from the Spanish Ministry of Science and Technology.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Songjie Shen ◽  
Yu Song ◽  
Bin Zhao ◽  
Yali Xu ◽  
Xinyu Ren ◽  
...  

Abstract Background Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation. Methods Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker. Results We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641. Conclusion The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment.


2020 ◽  
Author(s):  
Shahan Mamoor

Unraveling the host transcriptional response to viral infections is important for understanding host-pathogen interactions. We mined published microarray datasets (1-5) to identify conserved and specific differentially expressed genes in in vitro and in vivo models of coronavirus infections. We found significant transcriptional induction of the transcription factors BATF2 and FOXJ1 in Middle East Respiratory Syndrome (MERS) coronavirus infection in human cells in vitro; BATF2 was also differentially expressed in the lungs of mice infected with the Severe Acute Respiratory Syndrome (SARS) coronavirus 1 (SARS-CoV-1) but not in human cells infected with the human coronavirus HCoV-229E. These data highlight specific host induction of transcription factors by different members of the coronavirus family.


2020 ◽  
Author(s):  
Haidee Tinning ◽  
Alysha Taylor ◽  
Dapeng Wang ◽  
Bede Constantinides ◽  
Ruth Sutton ◽  
...  

ABSTRACTDuring the pre-implantation period of pregnancy in eutherian mammals, changes to the uterine endometrium are required (both at the transcriptional and protein level) to facilitate the endometrium becoming receptive to an implanting embryo. We know that the developing conceptus (embryo and extraembryonic membranes) produces proteins during this developmental stage. We hypothesised that this common process in early pregnancy in eutheria may be facilitated by highly conserved conceptus-derived proteins such as macrophage capping protein CAPG. More specifically, we propose that CAPG may share functionality in modifying the transcriptome of the endometrial epithelial cells to facilitate receptivity to implantation in species with different implantation strategies, such as human and bovine. A recombinant bovine form of CAPG (91% sequence identity between bovine and human) was produced and bovine endometrial epithelial (bEECs) and stromal (bESCs) cells and human endometrial epithelial cells (hEECs) were cultured for 24 h with or without rbCAPG. RNA sequencing and quantitative real-time PCR analysis was used to assess the transcriptional response to rbCAPG (Control, vehicle, CAPG 10, 100, 1000 ng/ml: n=3 biological replicates per treatment per species). Treatment of bEECs with CAPG resulted in changes to 1052 transcripts (629 increased and 423 decreased) compared to vehicle controls, including those previously only identified as regulated by interferon-tau, the pregnancy recognition signal in cattle. Treatment of hEECs with bovine CAPG increased expression of transcripts previously known to interact with CAPG in different systems (CAPZB, CAPZA2, ADD1 and ADK) compared with vehicle controls (P<0.05). In conclusion, we have demonstrated that CAPG, a highly conserved protein in eutherian mammals elicits a transcriptional response in the endometrial epithelium in two species with different implantation strategies that may facilitate uterine receptivity.


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