scholarly journals miRNA–mRNA network involved in folliculogenesis interactome: systems biology approach

Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Abolfazl Bahrami ◽  
Seyed Reza Miraie-Ashtiani ◽  
Mostafa Sadeghi ◽  
Ali Najafi
Keyword(s):  
Granulosa Cells ◽  
Regulatory Networks ◽  
Ovarian Follicle ◽  
Transcriptome Profiling ◽  
Computational Method ◽  
Bipartite Network ◽  
Data Sets ◽  
Target Mrnas ◽  
Master List ◽  
Reconstructed Network

At later phases of folliculogenesis, the mammalian ovarian follicle contains layers of granulosa cells surrounding an antral cavity. To better understand the molecular basis of follicular growth and granulosa cell maturation, we study transcriptome profiling of granulosa cells from small (<5 mm) and large (>10 mm) bovine follicles using simultaneous method of Affymetrix microarrays (24,128 probe sets) and RNA-Seq data sets. This study proposes a computational method to discover the functional miRNA–mRNA regulatory modules, that is, groups of miRNAs and their target mRNAs that are believed to take part cooperatively in post-transcriptional gene regulation under specific conditions. The reconstructed network was named Integrated miRNA–mRNA Bipartite Network. 277 genes and 6 key modules were disclosed through clustering for mRNA master list. The 66 genes are among the genes that belong to at least two modules. All these genes, being involved in at least one of the phenomena, namely cell survival, proliferation, metastasis and apoptosis, have an overexpression pattern (P < 0.01). For miRNA master list, a total of 172 sequences were differentially expressed (P < 0.01) between dominant (large) and each of subordinate (small) follicles. Within the follicle, these miRNAs were predominantly expressed in mural granulosa cells. Finally, predicted and validated targets of these miRNAs enriched in dominant (large) follicles were identified, which are mapped to signaling pathways involved in follicular cell proliferation, steroidogenesis, PI3K/AKT/mTOR and Ras/Raf/MEK/ERK. The identification of miRNAs and their target mRNAs and the construction of their regulatory networks may give new insights into biological procedures.

scholarly journals Human Granulosa Cells—Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1396
Author(s):  
Claudia Dompe ◽  
Magdalena Kulus ◽  
Katarzyna Stefańska ◽  
Wiesława Kranc ◽  
Błażej Chermuła ◽  
...  
Keyword(s):  
Stem Cells ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovarian Follicle ◽  
Cumulus Cells ◽  
Ovary Syndrome ◽  
Different Types ◽  
Metabolite Exchange ◽  
Reproductive Techniques ◽  
New Strategies

The ovarian follicle is the basic functional unit of the ovary, comprising theca cells and granulosa cells (GCs). Two different types of GCs, mural GCs and cumulus cells (CCs), serve different functions during folliculogenesis. Mural GCs produce oestrogen during the follicular phase and progesterone after ovulation, while CCs surround the oocyte tightly and form the cumulus oophurus and corona radiata inner cell layer. CCs are also engaged in bi-directional metabolite exchange with the oocyte, as they form gap-junctions, which are crucial for both the oocyte’s proper maturation and GC proliferation. However, the function of both GCs and CCs is dependent on proper follicular angiogenesis. Aside from participating in complex molecular interplay with the oocyte, the ovarian follicular cells exhibit stem-like properties, characteristic of mesenchymal stem cells (MSCs). Both GCs and CCs remain under the influence of various miRNAs, and some of them may contribute to polycystic ovary syndrome (PCOS) or premature ovarian insufficiency (POI) occurrence. Considering increasing female fertility problems worldwide, it is of interest to develop new strategies enhancing assisted reproductive techniques. Therefore, it is important to carefully consider GCs as ovarian stem cells in terms of the cellular features and molecular pathways involved in their development and interactions as well as outline their possible application in translational medicine.

scholarly journals Small RNA sequencing reveals distinct nuclear microRNAs in pig granulosa cells during ovarian follicle growth

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Derek Toms ◽  
Bo Pan ◽  
Yinshan Bai ◽  
Julang Li
Keyword(s):  
Granulosa Cells ◽  
Small Rna ◽  
High Throughput Sequencing ◽  
Ovarian Function ◽  
Ovarian Follicle ◽  
Small Rna Sequencing ◽  
Cell Fractionation ◽  
Steroid Synthesis ◽  
Non Coding Rna ◽  
Dna Binding Sites

AbstractNuclear small RNAs have emerged as an important subset of non-coding RNA species that are capable of regulating gene expression. A type of small RNA, microRNA (miRNA) have been shown to regulate development of the ovarian follicle via canonical targeting and translational repression. Little has been done to study these molecules at a subcellular level. Using cell fractionation and high throughput sequencing, we surveyed cytoplasmic and nuclear small RNA found in the granulosa cells of the pig ovarian antral preovulatory follicle. Bioinformatics analysis revealed a diverse network of small RNA that differ in their subcellular distribution and implied function. We identified predicted genomic DNA binding sites for nucleus-enriched miRNAs that may potentially be involved in transcriptional regulation. The small nucleolar RNA (snoRNA) SNORA73, known to be involved in steroid synthesis, was also found to be highly enriched in the cytoplasm, suggesting a role for snoRNA species in ovarian function. Taken together, these data provide an important resource to study the small RNAome in ovarian follicles and how they may impact fertility.

scholarly journals BioNetLink - An Architecture for Working with Network Data

2014 ◽  
Vol 11 (2) ◽  
pp. 68-79
Author(s):  
Matthias Klapperstück ◽  
Falk Schreiber
Keyword(s):  
Experimental Data ◽  
Biological Networks ◽  
Regulatory Networks ◽  
Large Data ◽  
Biological Data ◽  
Network Data ◽  
Data Sets ◽  
Dynamic Views ◽  
Gene Regulatory ◽  
Multiple Network

Summary The visualization of biological data gained increasing importance in the last years. There is a large number of methods and software tools available that visualize biological data including the combination of measured experimental data and biological networks. With growing size of networks their handling and exploration becomes a challenging task for the user. In addition, scientists also have an interest in not just investigating a single kind of network, but on the combination of different types of networks, such as metabolic, gene regulatory and protein interaction networks. Therefore, fast access, abstract and dynamic views, and intuitive exploratory methods should be provided to search and extract information from the networks. This paper will introduce a conceptual framework for handling and combining multiple network sources that enables abstract viewing and exploration of large data sets including additional experimental data. It will introduce a three-tier structure that links network data to multiple network views, discuss a proof of concept implementation, and shows a specific visualization method for combining metabolic and gene regulatory networks in an example.

scholarly journals Profiling Bioactivity of the ToxCast Chemical Library Using BioMAP Primary Human Cell Systems

2009 ◽  
Vol 14 (9) ◽  
pp. 1054-1066 ◽  
Author(s):  
Keith A. Houck ◽  
David J. Dix ◽  
Richard S. Judson ◽  
Robert J. Kavlock ◽  
Jian Yang ◽  
...  
Keyword(s):  
Human Cell ◽  
Regulatory Networks ◽  
Cell Types ◽  
Environmental Chemicals ◽  
Data Sets ◽  
Chemical Library ◽  
Data Set ◽  
Cell Systems ◽  
Disease Biology ◽  
Nfκb Pathway

The complexity of human biology has made prediction of health effects as a consequence of exposure to environmental chemicals especially challenging. Complex cell systems, such as the Biologically Multiplexed Activity Profiling (BioMAP) primary, human, cell-based disease models, leverage cellular regulatory networks to detect and distinguish chemicals with a broad range of target mechanisms and biological processes relevant to human toxicity. Here the authors use the BioMAP human cell systems to characterize effects relevant to human tissue and inflammatory disease biology following exposure to the 320 environmental chemicals in the Environmental Protection Agency’s (EPA’s) ToxCast phase I library. The ToxCast chemicals were assayed at 4 concentrations in 8 BioMAP cell systems, with a total of 87 assay endpoints resulting in more than 100,000 data points. Within the context of the BioMAP database, ToxCast compounds could be classified based on their ability to cause overt cytotoxicity in primary human cell types or according to toxicity mechanism class derived from comparisons to activity profiles of BioMAP reference compounds. ToxCast chemicals with similarity to inducers of mitochondrial dysfunction, cAMP elevators, inhibitors of tubulin function, inducers of endoplasmic reticulum stress, or NFκB pathway inhibitors were identified based on this BioMAP analysis. This data set is being combined with additional ToxCast data sets for development of predictive toxicity models at the EPA. ( Journal of Biomolecular Screening 2009:1054-1066)

Yolk transport in the ovarian follicle of the hen (Gallus domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase

1979 ◽  
Vol 39 (1) ◽  
pp. 257-272 ◽  
Author(s):  
M.M. Perry ◽  
A.B. Gilbert
Keyword(s):  
Basal Lamina ◽  
Granulosa Cells ◽  
Plasma Membranes ◽  
Ovarian Follicle ◽  
Cell Loss ◽  
Coated Vesicles ◽  
Morphological Alteration ◽  
Tissue Preparation ◽  
Very Low Density Lipoproteins ◽  
Thin Sections

Thin sections of the oocyte periphery and surrounding granulosa layer from 1–5 day preovulatory follicles were examined by transmission electron microscopy. With the use of certain procedures in tissue preparation, notably the tannic acid method, numerous particles in the range of 15–40 nm with a mean diameter of 27 nm were observed in both extra- and intracellularly. The particles were abundant in the granulosa basal lamina, in the spaces between the granulosa cells and in the perivitelline space. They appeared to adhere to the oolemma as a continuous double layer which was also observed to line the coated vesicles, 200–350 nm in diameter, invaginating from the oolemma. The layer of particles was not found on the plasma membranes of the granulosa cells, nor were particles present within the cells. In the peripheral cytoplasm of the oocyte the yolk spheres, ranging upwards from 250 nm diameter, were membrane-bound and contained tightly packed particles similar to those on the oolemma. Bodies displaying features intermediate between coated vesicles and yolk spheres suggested that, on entry into the cell, loss of the cytoplasmic coat and obliteration of the vesicular lumen gave rise to nascent yolk spheres which then fused together to form the larger spheres. The extracellular layer, coated vesicles and smaller yolk spheres were absent in oocytes fixed after a 10-min delay. The evidence indicated that 27-nm particles were transferred from the basal lamina to the oocyte surface via the intergranulosa cell channels, incorporated into the cell by adsorptive endocytosis and then transferred to the yolk spheres with little morphological alteration. The identity of the particles with very low density lipoproteins, the major components of the yolk solids, was discussed.

Ultrastructural observations of previtellogenic ovarian follicles of dove

Zygote ◽  
2004 ◽  
Vol 12 (4) ◽  
pp. 285-292 ◽  
Author(s):  
Otilia Zarnescu
Keyword(s):  
Electron Microscopy ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Complex Structure ◽  
Cortical Region ◽  
Multivesicular Bodies ◽  
Coated Pits ◽  
Zona Radiata ◽  
Theca Externa ◽  
Theca Interna

Dove ovarian follicle is a complex structure composed of oocyte surrounded by a somatic compartment consisting of theca externa, theca interna and granulosa. The structure of ovarian follicle (1 and 2 mm) of dove was studied by electron microscopy. The granulosa was pseudostratified in the 1-mm-diameter follicles and stratified with two or three irregular rows of cells in the 2-mm-diameter follicles. In the larger follicle indentations between oocyte and granulosa cells become more numerous and the microvilli of granulosa cell elongated to form a zona radiata with similarly elongated oocyte microvilli. Lining bodies were present at the tips of granulosa microvilli and in the cortical region of the oocyte. In the oocyte cortex were observed coated pits, coated vesicles, dense tubules, multivesicular bodies and primordial yolk spheres. Primordial yolk spheres may contain lining bodies and were observed fused with dense tubules and multivesicular bodies or associated with smooth cisternae.

scholarly journals Serum deprivation affects secretory activity of cultured porcine ovarian follicles and granulosa cells and their response to hormones

2009 ◽  
Vol 54 (No. 10) ◽  
pp. 455-460
Author(s):  
A.V. Sirotkin
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Secretory Activity ◽  
Ovarian Follicles ◽  
Serum Deprivation ◽  
Ovarian Cells ◽  
Igf I ◽  
Granulose Cells ◽  
Vitro Model

The aim of the present study is to understand the hormonal mechanisms of the effect of malnutrition on ovarian follicle functions. For this purpose, we examined the effect of malnutrition/serum deprivation, addition of metabolic hormones and gonadotropin (IGF-I, leptin and FSH) and their combination on the release of progesterone (P<sub>4</sub>), testosterone (T), estradiol (E<sub>2</sub>) and insulin-like growth factor I (IGF-I) by cultured whole ovarian follicles and on P<sub>4</sub> and IGF-I output by cultured granulosa cells isolated from porcine ovaries. It was observed that in ovarian follicles cultured with nutrients/serum addition of IGF-I reduced release of P<sub>4</sub>, but not of T or E<sub>2</sub>. Exogenous leptin reduced output of E<sub>2</sub>, but not of P<sub>4</sub> or T, and increased IGF-I output. No significant effect of FSH on release of steroid hormones by isolated follicles was found. Serum deprivation did not affect release of P<sub>4</sub>, but reduced output of T and E<sub>2</sub>, and promoted IGF-I release by cultured ovarian follicles. Addition of hormones failed to prevent the effect of malnutrition on the secretory activity of cultured ovarian follicles. In cultured granulose cells, all the tested hormones promoted release of both P<sub>4</sub> and IGF-I. Food restriction/serum deprivation reduced both P<sub>4</sub> and IGF-I output. Additions of either IGF-I, leptin and FSH prevented the inhibitory action of malnutrition on both P<sub>4</sub> and IGF-I release. The present observations (1) confirm the involvement of the hormones IGF-I, leptin and FSH in the control of secretory activity of ovarian cells, (2) demonstrate, that both isolated ovarian granulosa cells and whole follicles cultured in the absence of serum nutrients could be an adequate in-vitro model for studying the effect of malnutrition on ovarian secretory functions, and (3) suggest, that malnutrition could affect ovarian functions through changes in the release of ovarian hormones.

509. REGULATING MURINE FOLLICLE DEVELOPMENT BY STIMULATION OF THE JAK2/STAT3 SIGNAL TRANSDUCTION PATHWAY

2009 ◽  
Vol 21 (9) ◽  
pp. 108
Author(s):  
R. A. Keightley ◽  
B. Nixon ◽  
S. D. Roman ◽  
D. L. Russell ◽  
R. L. Robker ◽  
...  
Keyword(s):  
Significant Role ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Expression Patterns ◽  
Follicular Development ◽  
Janus Kinase ◽  
Follicle Development ◽  
Mrna Levels ◽  
Primordial Follicles ◽  
Stat3 Signalling

Follicular development requires the recruitment of primordial follicles into the growing follicle pool following initiation of multiple cytokine signalling pathways. Suppression of follicular development is thought to be key to maintaining the population of primordial follicles and allowing for controlled release of these follicles throughout the reproductive lifespan of the female. However, little is known of the processes and signalling molecules that suppress primordial follicle activation and early follicle growth. Our group has identified significant upregulation of the Janus Kinase 2 (JAK2)/ Signal Transducer and Activator of Transcription 3 (STAT3) signalling pathway inhibitor the Suppressor of Cytokine Signalling 4 (SOCS4) that coincides with the initial wave of follicular activation in theneonatal mouse ovary. Further studies by our group have localised the SOCS4 protein to the granulosa cells of activating and growing follicles, suggesting SOCS4 expression may be linked to follicular activation. We have focused on examining protein localisation and gene expression patterns of the eight SOCS family members CIS and SOCS1-7. We have recently demonstrated that co-culture of neonatal ovaries with Kit Ligand (KL) for 2 days increases the mRNA levels of all SOCS genes. We also demonstrated the co-localisation of SOCS2 proteins with the KL receptor c-kit in the mural granulosa cells of antral, and large pre-antral follicles suggesting a significant role for SOCS2 in the later stages of follicular development. We have also shown that culturing ovaries with the potent JAK2 inhibitor AG490 substantially reduces mRNA levels of all SOCS and STAT genes that we have so far measured. We hypothesise a significant role for JAK2/STAT3 signalling in promoting the activation and early growth of ovarian follicles. Our investigations have identified significant roles for JAK2/STAT3 and the SOCS family in the regulation of ovarian follicle development.

A survey on identification and quantification of alternative polyadenylation sites from RNA-seq data

2019 ◽  
Vol 21 (4) ◽  
pp. 1261-1276 ◽  
Author(s):  
Moliang Chen ◽  
Guoli Ji ◽  
Hongjuan Fu ◽  
Qianmin Lin ◽  
Congting Ye ◽  
...  
Keyword(s):  
Gene Expression Regulation ◽  
Simulated Data ◽  
Alternative Polyadenylation ◽  
Transcriptome Profiling ◽  
Systematic Evaluation ◽  
Data Sets ◽  
Rna Seq ◽  
Comprehensive Overview ◽  
Computational Approaches ◽  
The Status

Abstract Alternative polyadenylation (APA) has been implicated to play an important role in post-transcriptional regulation by regulating mRNA abundance, stability, localization and translation, which contributes considerably to transcriptome diversity and gene expression regulation. RNA-seq has become a routine approach for transcriptome profiling, generating unprecedented data that could be used to identify and quantify APA site usage. A number of computational approaches for identifying APA sites and/or dynamic APA events from RNA-seq data have emerged in the literature, which provide valuable yet preliminary results that should be refined to yield credible guidelines for the scientific community. In this review, we provided a comprehensive overview of the status of currently available computational approaches. We also conducted objective benchmarking analysis using RNA-seq data sets from different species (human, mouse and Arabidopsis) and simulated data sets to present a systematic evaluation of 11 representative methods. Our benchmarking study showed that the overall performance of all tools investigated is moderate, reflecting that there is still lot of scope to improve the prediction of APA site or dynamic APA events from RNA-seq data. Particularly, prediction results from individual tools differ considerably, and only a limited number of predicted APA sites or genes are common among different tools. Accordingly, we attempted to give some advice on how to assess the reliability of the obtained results. We also proposed practical recommendations on the appropriate method applicable to diverse scenarios and discussed implications and future directions relevant to profiling APA from RNA-seq data.

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