Abstract:
:Well-orchestrated epigenetic modifications during early development are essential for embryonic survival and postnatal growth. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, DNA methylation defects are of great concern. Despite the critical role of DNA methylation in determining embryonic development potential, the mechanisms underlying IVF-associated DNA methylation defects, however, remains largely elusive. We reported herein that repression of fibroblast growth factor (FGF) signaling as the main reason for IVF-associated DNA methylation defects. Comparative methylome analysis by postimplantation stage suggested that IVF mouse embryos undergo impaired de novo DNA methylation during implantation stage. Further analyses indicated that Dnmt3b, the main de novo DNA methyltransferase, was consistently inhibited during the transition from the blastocyst to postimplantation stage (Embryonic day 7.5, E7.5). Using blastocysts and embryonic stem cells (ESCs) as the model, we showed repression of FGF signaling is responsible for Dnmt3b inhibition and global hypomethylation during early development, and MEK/ERK-SP1 pathway plays an essential mediating role in FGF signaling-induced transcriptional activation of Dnmt3b. Supplementation of FGF2, which was exclusively produced in the maternal oviduct, into embryo culture medium significantly rescued Dnmt3b inhibition. Our study, using mouse embryos as the model, not only identifies FGF signaling as the main target for correcting IVF-associated epigenetic errors, but also highlights the importance of oviductal paracrine factors in supporting early embryonic development and improving in vitro culture system.
journal_name
Int J Biol Scijournal_title
International journal of biological sciencesauthors
Fu W,Yue Y,Miao K,Xi G,Zhang C,Wang W,An L,Tian Jdoi
10.7150/ijbs.51607subject
Has Abstractpub_date
2020-10-03 00:00:00pages
3085-3099issue
15issn
1449-2288pii
ijbsv16p3085journal_volume
16pub_type
杂志文章abstract::Osteosarcoma (OS) is considered the most common type of primary malignant bone tumor, which has an urgent need for more effective treatment. Recently, chitinase 3 like 1 (Chi3L1) expression has been found in a variety of cancer cells. However it is not known whether Chi3L1 regulates the STAT3 pathway in OS cells. Here...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.37781
更新日期:2020-01-01 00:00:00
abstract::Although it has been widely applied in identification of genes responsible for biomedically, economically, or even evolutionarily important complex and quantitative traits, traditional candidate gene approach is largely limited by its reliance on the priori knowledge about the physiological, biochemical or functional ...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.3.420
更新日期:2007-10-25 00:00:00
abstract::Dendritic cells (DCs) are the most potent specialized antigen-presenting cells as now known, which play a crucial role in initiating and amplifying both the innate and adaptive immune responses. Immunologically, the motilities and T cell activation capabilities of DCs are closely related to the resulting immune respon...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.33412
更新日期:2019-05-20 00:00:00
abstract::Solid tumors consist of various types of stromal cells in addition to cancer cells. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and play an essential role in tumor progression and metastasis in a variety of malignancies, including gastric cancer. However, the effects of CAFs on gastr...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.33750
更新日期:2019-08-22 00:00:00
abstract::Many organisms in extremely cold environments such as the Antarctic Pole have evolved antifreeze molecules to prevent ice formation. There are four types of antifreeze proteins (AFPs). Type-IV antifreeze proteins (AFP4s) are present also in certain temperate and even tropical fish, which has raised a question as to wh...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.9126
更新日期:2014-06-24 00:00:00
abstract::Background: The preoperative controlling nutritional status (CONUT) score and circulating tumour cell (CTC) status are associated with poor prognosis of colorectal cancer (CRC). The aim of the present study is to determine whether the combination of CONUT and CTC (CONUT-CTC) could better predict the prognosis of CRC p...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.33671
更新日期:2019-05-12 00:00:00
abstract::When pathogenic stresses are recognized by innate immune cells, inflammasomes are assembled and caspase-1 is activated, resulting in the conversion of pro-IL-18 into mature IL-18. Because natural killer (NK) cells express IL-18 receptors, IL-18 may play roles in immune functions of NK cells. In the present study, we e...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.22809
更新日期:2018-03-09 00:00:00
abstract::Emerging evidence has indicated that abnormal microRNAs (miRNAs) participated in carcinogenesis and tumor progression in hepatocellular carcinoma (HCC). Better understanding the association between miRNAs and HCC may contribute to discover novel therapeutic approaches for diagnosis and treatments. In the current study...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.33658
更新日期:2019-06-02 00:00:00
abstract::Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by many cytokines and growth factors and plays a key role in cell survival, proliferation, and differentiation. STAT3 activation is detected virtually in all rodent models of liver injury and in human liver diseases....
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.7.536
更新日期:2011-04-27 00:00:00
abstract::Telomere dysfunction is closely associated with human diseases such as cancer and ageing. Inappropriate changes in telomere length and/or structure result in telomere dysfunction. Telomeres have been considered to be transcriptionally silent, but it was recently demonstrated that mammalian telomeres are transcribed in...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.10528
更新日期:2015-02-05 00:00:00
abstract::Although the fibroblast growth factor (FGF) signaling axis plays important roles in cell survival, proliferation, and differentiation, the molecular mechanism underlying how the FGF elicits these diverse regulatory signals is not well understood. By using the Frs2α null mouse embryonic fibroblast (MEF) in conjunction ...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.7.1114
更新日期:2011-01-01 00:00:00
abstract::TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS) are two highly conserved ribonucleoproteins. Pathogenic mutations of the TDP-43 or the FUS gene are all linked to amyotrophic lateral sclerosis (ALS) that is characterized by progressive degeneration of motor neurons. To better understand the correlation of A...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.6.396
更新日期:2010-07-04 00:00:00
abstract::Since extracellular vesicles (EVs) were discovered in 1983 in sheep reticulocytes samples, they have gradually attracted scientific attention and become a topic of great interest in the life sciences field. EVs are small membrane particles, released by virtually every cell that carries a variety of functional molecule...
journal_title:International journal of biological sciences
pub_type: 杂志文章,评审
doi:10.7150/ijbs.39629
更新日期:2020-01-01 00:00:00
abstract::Farrerol has been shown to have antioxidative potential via Nrf2 activation, which in turn is involved in the prevention of hepatotoxicity. The purpose of the current study was to explore the protective effect of farrerol against acetaminophen-induced hepatotoxicity and its underlying mechanisms. Mice were used to eva...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.30677
更新日期:2019-01-29 00:00:00
abstract::Protein Kinase D3 (PRKD3) functions as an important oncogenic driver in invasive breast cancer, which is the leading cause of women mortality. However, PRKD3 regulating network is largely unknown. In this study, we systematically explored PRKD3 regulating networks via investigating phosphoproteome, interactome and tra...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.18472
更新日期:2017-05-16 00:00:00
abstract::Excessive inflammation induced by various risk factors is associated with the development of bronchopulmonary dysplasia (BPD). Caffeine exerts potent anti-inflammatory effects as a clinical preventive medicine for BPD. Recently, NLRP3 inflammasome activation has been demonstrated to be essential for the pathogenesis o...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.34211
更新日期:2019-06-02 00:00:00
abstract::Osteonecrosis of the femoral head (ONFH) represents a debilitating complication following glucocorticoid (GC)-based therapy. Synovial-derived mesenchymal stem cells (SMSCs) can exert protective effect in the animal model of GC-induced ONFH by inducing cell proliferation and preventing cell apoptosis. Recent studies in...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.16150
更新日期:2016-10-17 00:00:00
abstract::Collagen XXIV (Col24α1) is a recently discovered fibrillar collagen. It is known that mouse Col24α1 is predominantly expressed in the forming skeleton of the mouse embryo, as well as in the trabecular bone and periosteum of the newborn mouse. However, the role and mechanism of Col24α1 in osteoblast differentiation and...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.5136
更新日期:2012-01-01 00:00:00
abstract::We collected clinical data from 308 prostate cancer (PCa) patients to investigate the clinical characteristics and independent risk factors of bone metastasis (BM) and to establish a prediction model for BM of PCa and determine the necessity of bone scans. Univariate and multivariate analyses were performed based on a...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.27537
更新日期:2019-01-01 00:00:00
abstract::Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication caused by inflammation, but how it is initiated is still unclear. Several studies have shown that extracellular high mobility group box 1 (HMGB1), an important cytokine triggering inflammation, is overexpressed during the pathogenesis of S...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.50186
更新日期:2020-09-19 00:00:00
abstract::Foxp3⁺ regulatory T lymphocytes (Tregs) usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3(+) subset in peripheral blood mononuclear cells (PBMCs) and tumor tissues from extranodal NK/T cell lymphoma (ENK...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.7.1027
更新日期:2011-01-01 00:00:00
abstract::Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline med...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.15066
更新日期:2016-04-28 00:00:00
abstract:: Objectives: Skeletal development is a complex process. Little is known about the different response of limb or spine growth plate chondrocytes (LGP or SGP) to the estrogen level and the role of estrogen receptor (ER) during postnatal stage. Methods...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.17696
更新日期:2017-01-11 00:00:00
abstract::Tumor-associated macrophages (TAMs) are closely correlated with tumor occurrence, invasion, and metastasis. However, factors affecting the biological functions of TAMs in colorectal cancer (CRC) are incompletely understood. Here, we found that Wnt5a was mainly expressed on TAMs of tumor stroma but not on CRC cells. Su...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.40535
更新日期:2020-02-04 00:00:00
abstract::The objective of this study was to study the effect of diabetic hyperglycemia on astrocytes after forebrain ischemia. Streptozotocin (STZ)-injected hyperglycemic and vehicle-injected normoglycemic rats were subjected to 15 minutes of forebrain ischemia. The brains were harvested in sham-operated controls and in animal...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.7251
更新日期:2013-09-25 00:00:00
abstract::Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.16874
更新日期:2016-12-07 00:00:00
abstract::Versican, a ubiquitous component of the extracellular matrix (ECM), accumulates both in tumor stroma and cancer cells and is highly regulated by various cytokines. The aberrant expression of versican and its isoforms is known to modulate cell proliferation, differentiation, and migration, all of which are features of ...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.3579
更新日期:2012-01-01 00:00:00
abstract::Dengue virus (DENV) causes the most prevalent arthropod-borne viral disease of humans worldwide. Glycosphingolipids (GSLs) are involved in virus infection by regulating various steps of viral-host interaction. However, the distinct role of GSLs during DENV infection remains unclear. In this study, we used mouse melano...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.15641
更新日期:2016-05-25 00:00:00
abstract::Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic...
journal_title:International journal of biological sciences
pub_type: 杂志文章
doi:10.7150/ijbs.16472
更新日期:2016-10-25 00:00:00
abstract::The cephalochordate amphioxus occupies a central place in evolutionary thoughts to the origin of Vertebrates. With a prototypical vertebrate-like body plan and a preduplicative genome, the friendly lancelet seems to be in morphological and genetic motionless since its separation from the major branch of evolution that...
journal_title:International journal of biological sciences
pub_type: 社论
doi:10.7150/ijbs.2.30
更新日期:2006-01-01 00:00:00