010. Oocyte control of granulosa cell development and function

2005 ◽  
Vol 17 (9) ◽  
pp. 66
Author(s):  
J. J. Eppig ◽  
K. Sugiura
Keyword(s):  
Energy Source ◽  
Amino Acid ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Paracrine Factors ◽  
Subtraction Hybridization ◽  
Junctional Communication ◽  
And Function

Oocytes orchestrate the rate of follicular development and the patterns of gene expression by granulosa cells (GCs). There are two populations of GCs in large antral follicles: mural granulosa cells (MGCs) that line the ovarian follicle wall, and cumulus cells (CCs) closely associated with the oocyte. Subtraction hybridization was used to find transcripts more highly expressed in CCs than MGCs. Among the genes expressed more highly in CCs was one encoding an amino acid transporter (Slc38a3). Slc38a3 mRNA was not detected in oocytes. Expression of Slc38a3 mRNA was reduced in the CCs after removal of the oocyte and restored by co-culturing CCs with fully grown oocytes (FGOs). Alanine is one of the amino acids transported by SLC38A3. This amino acid is poorly transported across the oocyte plasma membrane, but gains access to the oocyte from the cumulus cells via gap junctional communication. Alanine transport into cumulus cells was promoted by paracrine factors secreted by FGOs, but not by growing oocytes (GOs) from preantral follicles. Thus FGOs promote the transport of alanine into CCs, and this amino acid is then passed on to the oocyte via gap junctions. Transcripts encoding enzymes in the glycolytic pathway were also more highly expressed in CCs than MGCs. FGOs, but not GOs, promote elevated expression of some of these transcripts. Likewise, FGOs promote both glycolysis and oxidative phosphorylation by isolated CCs and MGCs. Oocytes do not effectively utilize glucose as an energy source, and oocytes require the presence of CCs to resume meiosis when glucose is the only energy source present. In contrast, oocytes can resume meiosis in the absence of CCs when pyruvate is the sole energy source. Thus oocytes apparently promote glycolysis by their companion granulosa cells to provide energy for their own development. In addition, this may be one way that oocytes coordinate their development with that of follicular somatic components. Supported by Grants HD23839 and HD44416 from the NICHD.

scholarly journals Transcriptomic profile of genes encoding proteins responsible for regulation of cells differentiation and neurogenesis in vivo and in vitro – an oocyte model approach

2020 ◽  
Vol 8 (1) ◽  
pp. 1-11
Author(s):  
Lisa Moncrieff ◽  
Ievgeniia Kocherova ◽  
Artur Bryja ◽  
Wiesława Kranc ◽  
Joanna Perek ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Cumulus Cells ◽  
Paracrine Factors ◽  
Gene Markers ◽  
Genes Encoding ◽  
Porcine Oocyte ◽  
Micro Analysis

AbstractThe growth and development of the oocyte is essential for the ovarian follicle. Cumulus cells (CCs) - a population of granulosa cells - exchange metabolites, proteins and oocyte-derived paracrine factors with the oocyte through gap junctions, to contribute to the competency and health of the oocyte. This bi-directional communication of the cumulus-oocyte complex could be better understood through the micro-analysis of a porcine oocyte gene expression before in vitro maturation (IVM) and after. Additionally, the study of the somatic and gamete cells differentiation capability into neuronal lineage would be promising for future stem cell research as granulosa cells are easily accessible waste material from in vitro fertilization (IVF) procedures. Therefore, in this study, the oocytes of 45 pubertal Landrace gilts were isolated and the protein expression of the COCs were analyzed through micro-analysis techniques. Genes belonging to two ontological groups: neuron differentiation and negative regulation of cell differentiation have been identified which have roles in proliferation, migration and differentiation. Twenty identified porcine oocyte genes (VEGFA, BTG2, MCOLN3, EGR2, TGFBR3, GJA1, FST, CTNNA2, RTN4, MDGA1, KIT, RYK, NOTCH2, RORA, SMAD4, ITGB1, SEMA5A, SMARCA1, WWTR1 and APP) were found to be down-regulated after the transition of IVM compared to in vitro. These results could be applied as gene markers for the proliferation, migration and differentiation occurring in the bi-directional communication between the oocyte and CCs.Running title: Differentiation and neurogenesis in oocyte cells

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.

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.

scholarly journals Expression and Localization of Secreted Frizzled-Related Protein-4 in the Rodent Ovary: Evidence for Selective Up-Regulation in Luteinized Granulosa Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4597-4606 ◽  
Author(s):  
Minnie Hsieh ◽  
Sabine M. Mulders ◽  
Robert R. Friis ◽  
Arun Dharmarajan ◽  
JoAnne S. Richards
Keyword(s):  
Chorionic Gonadotropin ◽  
Granulosa Cells ◽  
Human Chorionic Gonadotropin ◽  
Follicular Development ◽  
Corpora Lutea ◽  
Related Protein ◽  
Rich Domain ◽  
And Function ◽  
Periovulatory Follicles

Secreted frizzled-related protein-4 (sFRP-4) belongs to a family of soluble proteins that have a Frizzled-like cysteine-rich domain and function as modulators of Wnt-Frizzled (Fz) signals. As several Wnts and Fz are expressed at defined stages of follicular development in rodent ovaries, these studies were undertaken to evaluate the hormone-regulated expression and localization of sFRP-4. In the mouse ovary, the expression of sFRP-4 mRNA was up-regulated in granulosa cells of large antral follicles after human chorionic gonadotropin administration and was also elevated in corpora lutea, as determined by RT-PCR and in situ hybridization analyses. In hypophysectomized rat ovaries, sFRP-4 expression was similarly induced by human chorionic gonadotropin and further up-regulated by PRL. PRL also stimulated the secretion of sFRP-4 protein from luteinized rat granulosa cells in culture. Therefore, regulation of sFRP-4 by LH and PRL may be important for modulating Fz-1, which is known to be expressed in periovulatory follicles, and Wnt-4/Fz-4, which are expressed in corpora lutea.

scholarly journals Profiling of superoxide dismutase isoenzymes in compartments of the developing bovine antral follicles

Reproduction ◽  
2010 ◽  
Vol 139 (5) ◽  
pp. 871-881 ◽  
Author(s):  
Catherine M H Combelles ◽  
Emily A Holick ◽  
Louis J Paolella ◽  
David C Walker ◽  
Qiaqia Wu
Keyword(s):  
Superoxide Dismutase ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Antral Follicle ◽  
Supporting Evidence ◽  
Sod Activity ◽  
Antral Follicles ◽  
Sod Isoforms

The antral follicle constitutes a complex and regulated ovarian microenvironment that influences oocyte quality. Oxidative stress is a cellular state that may play a role during folliculogenesis and oogenesis, although direct supporting evidence is currently lacking. We thus evaluated the expression of the three isoforms (SOD1, SOD2, and SOD3) of the enzymatic antioxidant superoxide dismutase in all the cellular (granulosa cells, cumulus cells, and oocytes) and extracellular (follicular fluid) compartments of the follicle. Comparisons were made in bovine ovaries across progressive stages of antral follicular development. Follicular fluid possessed increased amounts of SOD1, SOD2, and SOD3 in small antral follicles when compared with large antral follicles; concomitantly, total SOD activity was highest in follicular fluids from smaller diameter follicles. SOD1, SOD2, and SOD3 proteins were expressed in granulosa cells without any fluctuations in follicle sizes. All three SOD isoforms were present, but were distributed differently in oocytes from small, medium, or large antral follicles. Cumulus cells expressed high levels of SOD3, some SOD2, but no detectable SOD1. Our studies provide a temporal and spatial expression profile of the three SOD isoforms in the different compartments of the developing bovine antral follicles. These results lay the ground for future investigations into the potential regulation and roles of antioxidants during folliculogenesis and oogenesis.

scholarly journals Mouse Oocytes Enable LH-Induced Maturation of the Cumulus-Oocyte Complex via Promoting EGF Receptor-Dependent Signaling

2010 ◽  
Vol 24 (6) ◽  
pp. 1230-1239 ◽  
Author(s):  
You-Qiang Su ◽  
Koji Sugiura ◽  
Qinglei Li ◽  
Karen Wigglesworth ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Growth Factors ◽  
Granulosa Cells ◽  
Egf Receptor ◽  
Cumulus Cells ◽  
Wild Type ◽  
Paracrine Factors ◽  
Cumulus Oocyte Complex ◽  
Egfr Expression

Abstract LH triggers the maturation of the cumulus-oocyte complex (COC), which is followed by ovulation. These ovarian follicular responses to LH are mediated by epidermal growth factor (EGF)-like growth factors produced by granulosa cells and require the participation of oocyte-derived paracrine factors. However, it is not clear how oocytes coordinate with the EGF receptor (EGFR) signaling to achieve COC maturation. The aim of the present study was to test the hypothesis that oocytes promote the expression of EGFR by cumulus cells, thus enabling them to respond to the LH-induced EGF-like peptides. Egfr mRNA and protein expression were dramatically reduced in cumulus cells of mutant mice deficient in the production of the oocyte-derived paracrine factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). Moreover, microsurgical removal of oocytes from wild-type COCs dramatically reduced expression of Egfr mRNA and protein, and these levels were restored by either coculture with oocytes or treatment with recombinant GDF9 or GDF9 plus recombinant BMP15. Blocking Sma- and Mad-related protein (SMAD)2/3 phosphorylation in vitro inhibited Egfr expression in wild-type COCs and in GDF9-treated wild-type cumulus cells, and conditional deletion of Smad2 and Smad3 genes in granulosa cells in vivo resulted in the reduction of Egfr mRNA in cumulus cells. These results indicate that oocytes promote expression of Egfr in cumulus cells, and a SMAD2/3-dependent pathway is involved in this process. At least two oocyte-derived growth factors, GDF9 and BMP15, are required for EGFR expression by cumulus cells.

scholarly journals HIF-1α Protects Granulosa Cells From Hypoxia-Induced Apoptosis During Follicular Development by Inducing Autophagy

2021 ◽  
Vol 9 ◽  
Author(s):  
Zonghao Tang ◽  
Renfeng Xu ◽  
Zhenghong Zhang ◽  
Congjian Shi ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Mammalian Cells ◽  
Caspase 3 ◽  
Ovarian Follicle ◽  
Hypoxia Inducible Factor ◽  
Follicular Development ◽  
B Cell Lymphoma ◽  
Underlying Mechanism

Owing to the avascular structure of the ovarian follicle, proliferation of granulosa cells (GCs) and development of follicles occur under hypoxia, which is obviously different from the cell survival requirements of most mammalian cells. We hypothesized that autophagy may exert an inhibitory effect on GC apoptosis. To decipher the underlying mechanism, we constructed a rat follicular development model using pregnant mare serum gonadotropin and a cell culture experiment in hypoxic conditions (3% O2). The present results showed that the autophagy level was obviously increased and was accompanied by the concomitant elevation of hypoxia inducible factor (HIF)-1α and BNIP3 (Bcl-2/adenovirus E1B 19kDa-interacting protein 3) in GCs during follicular development. The levels of Bax (Bcl2-associated X) and Bcl-2 (B-cell lymphoma-2) were increased, while the activation of caspase-3 exhibited no obvious changes during follicular development. However, inhibition of HIF-1α attenuated the increase in Bcl-2 and promoted the increase in Bax and cleaved caspase-3. Furthermore, we observed the downregulation of BNIP3 and the decrease in autophagy after treatment with a specific HIF-1α activity inhibitor (echinomycin), indicating that HIF-1α/BNIP3 was involved in autophagy regulation in GCs in vivo. In an in vitro study, we also found that hypoxia did not obviously promote GC apoptosis, while it significantly enhanced the activation of HIF-1α/BNIP3 and the induction of autophagy. Expectedly, this effect could be reversed by 3-methyladenine (3-MA) treatment. Taken together, these findings demonstrated that hypoxia drives the activation of HIF-1α/BNIP3 signaling, which induces an increase in autophagy, protecting GC from apoptosis during follicular development.

187 EXPRESSION AND REGULATION OF THE FIBROBLAST GROWTH FACTOR GENE FAMILY DURING MOUSE FOLLICULAR DEVELOPMENT

2013 ◽  
Vol 25 (1) ◽  
pp. 243
Author(s):  
S. Furukawa ◽  
K. Naito ◽  
K. Sugiura
Keyword(s):  
Gene Family ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Mouse Ovary ◽  
Expression Levels ◽  
Before And After ◽  
Equine Chorionic Gonadotropin

Recent studies have shown the critical roles of fibroblast growth factors (FGFs), including FGF8 produced by oocytes, in regulating follicular development. However, the expression and regulation of the FGF gene family, which consists of 22 ligands and 4 receptors, in the mouse ovary have not been well understood. The aim of the present study was to assess the expression and regulation of FGF ligands and receptors in the mouse ovary. Transcript levels of FGF ligands and receptors in immature (3-week-old) and adult (7- to 8-week-old) ovaries as well as other tissues of B6/DBA2F1 mice were analysed with RT-PCR. Furthermore, expression levels of FGF receptors in cumulus cells (CC) and mural granulosa cells (MG) before and after equine chorionic gonadotropin (eCG) treatment were determined with RT-quantitative PCR. Among 21 FGF ligands examined, 12 and 9 transcripts were detectable in immature and adult ovaries, respectively. More FGF ligands were detected in ovary, testis, heart, and brain compared to other tissues, including liver and spleen. Transcripts of all 4 FGF receptors (Fgfr1–4) were detectable in both immature and adult ovaries. Expression levels of Fgfr1 and Fgfr2 were significantly higher in MG compared with CC before and after the eCG treatment. Levels of Fgfr4 were comparable between MG and CC before the eCG treatment, but became significantly different with higher expression levels in MG after the eCG treatment. Fgfr3 transcripts were barely detectable in CC and MG. Overall levels of Fgfr1 in granulosa cells (CC and MG) were downregulated by eCG treatment, whereas those of Fgfr2 and Fgfr4 were upregulated. In summary, many FGF ligands are expressed, at least in mRNA levels, in mouse ovaries. Moreover, the expression levels of Fgfr transcripts in granulosa cells are dynamically regulated during follicular development.

Expression and function of lysophosphatidic acid in granulosa cells of the bovine ovarian follicle

2014 ◽  
Author(s):  
Izabela Woclawek-Potocka ◽  
Emilia Sinderewicz ◽  
Dorota Boruszewska ◽  
Ilona Kowalczyk-Zieba ◽  
Joanna Staszkiewicz ◽  
...  
Keyword(s):  
Lysophosphatidic Acid ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
And Function

scholarly journals Characteristic of factors influencing the proper course of folliculogenesis in mammals

2018 ◽  
Vol 6 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Marta Rybska ◽  
Sandra Knap ◽  
Maurycy Jankowski ◽  
Michal Jeseta ◽  
Dorota Bukowska ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Follicular Development ◽  
Ovarian Follicles ◽  
Postnatal Life ◽  
Metabolic Hormones ◽  
Corona Radiata ◽  
Mural Cells ◽  
Thecal Cells ◽  
Reproductive Processes

AbstractFolliculogenesis is the process of ovarian follicle formation,, taking presence during foetal period. During the follicular development, oogoniums undergo meiosis and oocytes are formed. In the ovaries of new born sows, primary and secondary follicles are present and, 90 days after birth, tertiary follicles appear. During development in the ovarian follicles growth of granulosa cells and differentiation of the thecal cells can be observed. A cavity filled with follicular fluid appears. Granulosa cells are divided into: mural cells and corona radiata, which together with the oocyte form the cumulus oophorus. Corona radiata cells, mural layers and oolemma contact each other by a network of gap junctions. Secreted from the pituitary gland, FSH and LH gonadotropin hormones act on receptors located in granular and follicular cells. In the postnatal life tertiary follicles and Graafian follicles are formed. When the follicle reaches a diameter of 1 mm, further growth depends on the secretion of gonadotropins. Mature ovarian follicles produce: progestins, androgens and oestrogens. The growth, differentiation and steroidogenic activity of ovarian follicles, in addition to FSH and LH, is also affected by prolactin, oxytocin, steroid and protein hormones, numerous proteins from the cytokine and interleukin family, metabolic hormones like insulin, glucocorticoids, leptin, thyroid hormones and growth hormones. Despite numerous studies, many processes related to folliculogenesis have not been discovered Learning the mechanisms regulating reproductive processes would allow to easily distinguish pathological processes and discover more and more genes and mechanisms of their expression in cells that build ovarian follicles.

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