scholarly journals Syndecan 1 represses cell growth and FSH responsiveness in human granulosa cells

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. 797-808 ◽  
Author(s):  
Simon Colombe ◽  
Laura Houllier ◽  
Emmanuelle Fleurot ◽  
Guénaëlle Levallet ◽  
Annie Benhaïm ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Morphological Changes ◽  
Heparan Sulphate ◽  
Follicular Development ◽  
Antral Follicle ◽  
Gene Expressions ◽  
Cytoskeletal Organization ◽  
Cellular Processes ◽  
Proliferation And Differentiation ◽  
Small Antral Follicle

Albeit devoid of intrinsic catalytic activity, the transmembrane heparan sulphate proteoglycan syndecan 1 plays critical roles in cellular processes such as extracellular matrix crosstalk, cytoskeletal organization, cell spreading, proliferation and differentiation. During the ovarian cycle, the expression of syndecan 1 in granulosa cells shows cyclic variation suggesting that it might fulfil specific roles in follicle development. To investigate its physiological roles on granulosa cells, syndecan 1 was overexpressed in human granulosa cell line KGN which retains features of granulosa cells from small antral follicle such as estradiol (E2) synthesis and low expression of functional FSH receptor (FSHR). We demonstrated that overexpression of syndecan 1 in immature granulosa cells (KGN-SDC1) induces a profound alteration in their intrinsic characteristics including enhanced spreading and attachment, both associated with a reduced growth rate. Flow cytometry analysis revealed that syndecan 1 overexpression increases the percentage of KGN cells in quiescent phase. This partial cell cycle exit is concordant with downregulated levels of CCND1 and CDK4 and upregulated expression of CDK inhibitor CDKN1A. In parallel both unstimulated and FSH-induced E2 synthesis are reduced in KGN-SDC1 through both repression of CYP19A1 and FSHR mRNA associated with decreased levels of potential regulators NR5A1 and ESR2. Additionally, we provide evidence that transient cAMP accumulation reduction in cells overexpressing syndecan 1 is accompanied by an increase in cAMP-hydrolysing PDE activity. Our results demonstrated that syndecan 1 might regulate differentiation of granulosa cells and follicular development by means of various mechanisms involving morphological changes, control of signalling pathways and alterations in gene expressions. Free French abstract: A French translation of this abstract is freely available at http://www.reproduction-online.org/content/153/6/797/suppl/DC2

Ultrastructure of the basal lamina of bovine ovarian follicles and its relationship to the membrana granulosa

Reproduction ◽  
2000 ◽  
pp. 221-228 ◽  
Author(s):  
HF Irving-Rodgers ◽  
RJ Rodgers
Keyword(s):  
Basal Lamina ◽  
Granulosa Cells ◽  
Light And Electron Microscopy ◽  
Single Layer ◽  
Antral Follicle ◽  
Basal Cells ◽  
Preantral Follicles ◽  
Antral Follicles ◽  
Cellular Processes ◽  
Innermost Layer

Different morphological phenotypes of follicular basal lamina and of membrana granulosa have been observed. Ten preantral follicles (< 0. 1 mm), and 17 healthy and six atretic antral follicles (0.5-12 mm in diameter) were processed for light and electron microscopy to investigate the relationship the between follicular basal lamina and membrana granulosa. Within each antral follicle, the shape of the basal cells of the membrana granulosa was uniform, and either rounded or columnar. There were equal proportions of follicles </= 4 mm in diameter with columnar basal cells and with rounded basal cells. Larger follicles had only rounded basal cells. Conventional basal laminae of a single layer adjacent to the basal granulosa cells were observed in healthy follicles at the preantral and antral stages. However, at the preantral stage, the conventional types of basal lamina were enlarged or even partially laminated. A second type of basal lamina, described as 'loopy', occurred in about half the preantral follicles and in half the antral follicles </= 4 mm diameter. 'Loopy' basal laminae were not observed in larger follicles. 'Loopy' basal laminae were composed of basal laminae aligning the basal surface of basal granulosa cells, but with additional layers or loops often branching from the innermost layer. Each loop was usually < 1 microm long and had vesicles (20-30 nm) attached to the inner aspect. Basal cellular processes were also common, and vesicles could be seen budding off from these processes. In antral follicles, conventional basal laminae occurred in follicles with rounded basal granulosa cells. Other follicles with columnar cells, and atretic follicles, had the 'loopy' basal lamina phenotype. Thus, follicles have different basal laminae that relate to the morphology of the membrana granulosa.

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.

Growth factor receptor-bound protein 14: a potential new gene associated with oocyte competence

Zygote ◽  
2013 ◽  
Vol 22 (2) ◽  
pp. 103-109 ◽  
Author(s):  
Paulo Roberto Antunes Rosa ◽  
Rodrigo Camponogara Bohrer ◽  
Matheus Pedrotti De Cesaro ◽  
Karina Gutierrez ◽  
Rogério Ferreira ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Mrna Expression ◽  
Growth Factor Receptor ◽  
Follicular Development ◽  
Antral Follicle ◽  
Protein Family ◽  
Oocyte Competence ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
New Gene

SummaryThe Grb14 protein is a member of the Grb7 protein family. This protein family acts by binding to tyrosine kinase receptors, promoting cell proliferation and differentiation. There is evidence of the involvement of tyrosine kinase factors in the bovine oocyte maturation process. However, Grb14 has not been studied for bovine cumulus–oocyte complexes (COCs). The aim of the present study was to characterize Grb14 mRNA expression in bovine COCs during follicular development. Furthermore, we demonstrated that the expression of Grb14 mRNA is not regulated by estradiol. mRNA expression of Grb14 was assessed in 480 COCs from follicles of different sizes (1–3, 4–6, 6–8 or >8 mm) by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Grb14 mRNA expression decreased in COCs throughout follicular growth (P < 0.05). The role of estradiol in the expression of Grb14 mRNA in COCs was studied. Grb14 mRNA abundance did not differ in COCs cultured in the presence or absence of 17β-estradiol or fulvestrant. In conclusion, we showed that Grb14 mRNA is downregulated in COCs during antral follicle development, a finding that suggests a role for Grb14 in oocyte competence.

A mouse model reveals the events and underlying regulatory signals during the gonadotrophin-dependent phase of follicle development

2020 ◽  
Vol 26 (12) ◽  
pp. 920-937
Author(s):  
Yingjun Chen ◽  
Xiaodong Wang ◽  
Chan Yang ◽  
Qinghua Liu ◽  
Zaohong Ran ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Granulosa Cells ◽  
Growth Phase ◽  
Rapid Growth ◽  
Antral Follicle ◽  
Sequencing Data ◽  
Proliferation And Differentiation ◽  
Preparation Phase ◽  
Synthesis And Processing ◽  
Transcriptomic Level

ABSTRACT During folliculogenesis, the gonadotrophin (GTH)-dependent phase begins at the small antral follicle stage and ends with Graafian follicles. In this study, pregnant mare’s serum GTH was used to induce GTH-dependent folliculogenesis in mice, following which the developmental events that follicles undergo, as well as the underlying regulatory signals, were investigated at both the morphological and transcriptomic level. GTH-dependent folliculogenesis consisted of three phases: preparation, rapid growth and decelerated growth. In the preparation phase, comprising the first 12 h, granulosa cells completed the preparations for proliferation and differentiation, shifted energy metabolism to glycolysis, and reduced protein synthesis and processing. The rapid growth phase lasted from 12 to 24 h; in this phase, granulosa cells completed their proliferation, and follicles acquired the capacity for estradiol secretion and ovulation. Meanwhile, the decelerating growth phase occurred between 24 and 48 h of GTH-dependent folliculogenesis. In this phase, the proliferation and expansion of the follicular antrum were reduced, energy metabolism was shifted to oxidative phosphorylation, and cell migration and lipid metabolism were enhanced in preparation for luteinization. We also revealed the key signaling pathways that regulate GTH-dependent folliculogenesis and elucidated the activation sequence of these pathways. A comparison of our RNA-sequencing data with that reported for humans suggested that the mechanisms involved in mouse and human folliculogenesis are evolutionarily conserved. In this study, we draw a detailed atlas of GTH-dependent folliculogenesis, thereby laying the foundation for further investigation of the regulatory mechanisms underlying this process.

Morphological Changes in the Rat Granulosa Cell Surface During Differentiation Induced by Estradiol and Gonadotropins

1977 ◽  
Vol 35 ◽  
pp. 484-485
Author(s):  
P. Bagavandoss ◽  
JoAnne S. Richards ◽  
A. Rees Midgley
Keyword(s):  
Cell Surface ◽  
Granulosa Cell ◽  
Morphological Changes ◽  
Follicular Development ◽  
Female Rats ◽  
Functional Changes ◽  
Group 4 ◽  
Group 3 ◽  
Group 5 ◽  
Group 2

During follicular development in the mammalian ovary, several functional changes occur in the granulosa cells in response to steroid hormones and gonadotropins (1,2). In particular, marked changes in the content of membrane-associated receptors for the gonadotropins have been observed (1).We report here scanning electron microscope observations of morphological changes that occur on the granulosa cell surface in response to the administration of estradiol, human follicle stimulating hormone (hFSH), and human chorionic gonadotropin (hCG).Immature female rats that were hypophysectcmized on day 24 of age were treated in the following manner. Group 1: control groups were injected once a day with 0.1 ml phosphate buffered saline (PBS) for 3 days; group 2: estradiol (1.5 mg/0.2 ml propylene glycol) once a day for 3 days; group 3: estradiol for 3 days followed by 2 days of hFSH (1 μg/0.1 ml) twice daily, group 4: same as in group 3; group 5: same as in group 3 with a final injection of hCG (5 IU/0.1 ml) on the fifth day.

scholarly journals MicroRNA Mediating Networks in Granulosa Cells Associated with Ovarian Follicular Development

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Baoyun Zhang ◽  
Long Chen ◽  
Guangde Feng ◽  
Wei Xiang ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Granulosa Cells ◽  
Messenger Rna ◽  
Expression Patterns ◽  
Follicular Development ◽  
Functional Networks ◽  
Signal Pathways ◽  
Differentially Expressed Mirnas ◽  
Selection Of

Ovaries, which provide a place for follicular development and oocyte maturation, are important organs in female mammals. Follicular development is complicated physiological progress mediated by various regulatory factors including microRNAs (miRNAs). To demonstrate the role of miRNAs in follicular development, this study analyzed the expression patterns of miRNAs in granulosa cells through investigating three previous datasets generated by Illumina miRNA deep sequencing. Furthermore, via bioinformatic analyses, we dissected the associated functional networks of the observed significant miRNAs, in terms of interacting with signal pathways and transcription factors. During the growth and selection of dominant follicles, 15 dysregulated miRNAs and 139 associated pathways were screened out. In comparison of different styles of follicles, 7 commonly abundant miRNAs and 195 pathways, as well as 10 differentially expressed miRNAs and 117 pathways in dominant follicles in comparison with subordinate follicles, were collected. Furthermore, SMAD2 was identified as a hub factor in regulating follicular development. The regulation of miR-26a/b onsmad2messenger RNA has been further testified by real time PCR. In conclusion, we established functional networks which play critical roles in follicular development including pivotal miRNAs, pathways, and transcription factors, which contributed to the further investigation about miRNAs associated with mammalian follicular development.

scholarly journals The role of IGFs in the regulation of ovarian follicular growth in the brushtail possum (Trichosurus vulpecula)

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 295-303 ◽  
Author(s):  
Jennifer L Juengel ◽  
Lisa J Haydon ◽  
Brigitta Mester ◽  
Brian P Thomson ◽  
Michael Beaumont ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Antral Follicle ◽  
Brushtail Possum ◽  
Follicular Growth ◽  
Theca Cells ◽  
Ovarian Follicular Growth

IGFs are known to be key regulators of ovarian follicular growth in eutherian mammals, but little is known regarding their role in marsupials. To better understand the potential role of IGFs in the regulation of follicular growth in marsupials, expression of mRNAs encoding IGF1, IGF2, IGF1R, IGF-binding protein 2 (IGFBP2), IGFBP4 and IGFBP5 was localized by in situ hybridization in developing ovarian follicles of the brushtail possum. In addition, the effects of IGF1 and IGF2 on granulosa cell function were tested in vitro. Both granulosa and theca cells synthesize IGF mRNAs, with the theca expressing IGF1 mRNA and granulosa cell expressing IGF2 mRNA. Oocytes and granulosa cells express IGF1R. Granulosa and theca cells expressed IGFBP mRNAs, although the pattern of expression differed between the BPs. IGFBP5 mRNA was differentially expressed as the follicles developed with granulosa cells of antral follicles no longer expressing IGFBP5 mRNA, suggesting an increased IGF bioavailability in the antral follicle. The IGFBP protease, PAPPA mRNA, was also expressed in granulosa cells of growing follicles. Both IGF1 and IGF2 stimulated thymidine incorporation but had no effect on progesterone production. Thus, IGF may be an important regulator of ovarian follicular development in marsupials as has been shown in eutherian mammals.

Effects of Echinomycin on PCNA-Dependent Follicular Development in PMSG-Induced Sprague-Dawley Rats

2014 ◽  
Vol 998-999 ◽  
pp. 228-232
Author(s):  
Zheng Hong Zhang ◽  
Fan Wang ◽  
Yan Qing Wu ◽  
Zong Hao Tang ◽  
Qing Qiang Lin ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Follicular Development ◽  
Antral Follicle ◽  
Binding Activity ◽  
Nuclear Antigen ◽  
Sprague Dawley ◽  
Dna Binding Activity ◽  
Molecule Inhibitor ◽  
Protein Expressions ◽  
Serum Gonadotropin

Echinomycin (Ech) is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in the regulation of ovarian functions in mammals. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated proliferation cell nuclear antigen (PCNA) expressions contributed to the follicular development in the rat ovary primed by pregnant mare serum gonadotropin (PMSG). Through the histological examination, the decrease of growing and antral follicle numbers was found after Ech treatment both in control and PMSG treated groups. And then PCNA mRNA and protein expressions were found to significantly increase in the ovaries treated with PMSG, and the similar changes were found in HIF-1alpha mRNA and protein expressions, indicating PMSG-induced follicular development may be through HIF-1alpha/PCNA signaling. Furthermore, PCNA expression was found to significantly decrease in the ovaries after Ech treatment, while HIF-1alpha mRNA and protein expression was no obviously changes. Further analysis found the changes of PCNA expression were consistent with HIF-1 activity in the ovaries, further suggesting the regulatory roles in the follicular development. Taken together, these results demonstrated this HIF-1alpha-mediated PCNA expression is one of the important mechanisms regulating the ovarian follicular development in mammals. Keywords: HIF-1alpha; PCNA; echinomycin; HIF prolyl hyodroxylase acitvity; follicular development

scholarly journals Direct Effects of Estradiol and Tamoxifen on Gene Expressions of Inhibin .ALPHA.- and .BETA.A-Subunits in Rat Granulosa Cells In Vitro.

1996 ◽  
Vol 43 (6) ◽  
pp. 621-628 ◽  
Author(s):  
SHINTARO TATE ◽  
NOBUHIKO SUGANUMA ◽  
MADOKA FURUHASHI ◽  
TOMOKO ANDO ◽  
YOSHIMASA ASADA ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Direct Effects ◽  
Gene Expressions

scholarly journals AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia

Reproduction ◽  
2014 ◽  
Vol 147 (1) ◽  
pp. 73-80 ◽  
Author(s):  
JongYeob Choi ◽  
MinWha Jo ◽  
EunYoung Lee ◽  
DooSeok Choi
Keyword(s):  
Cell Death ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Apoptotic Cell ◽  
Follicular Development ◽  
Negative Regulator ◽  
Metabolic Clearance ◽  
Akt Inhibitor ◽  
Western Blots

In this study, we examined whether granulosa cell autophagy during follicular development and atresia was regulated by the class I phosphoinositide-3 kinase/protein kinase B (AKT) pathway, which is known to control the activity of mammalian target of rapamycin (mTOR), a major negative regulator of autophagy. Ovaries and granulosa cells were obtained using an established gonadotropin-primed immature rat model that induces follicular development and atresia. Autophagy was evaluated by measuring the expression level of microtubule-associated protein light chain 3-II (LC3-II) using western blots and immunohistochemistry. The activity of AKT and mTOR was also examined by observing the phosphorylation of AKT and ribosomal protein S6 kinase (S6K) respectively. After gonadotropin injection, LC3-II expression was suppressed and phosphorylation of AKT and S6K increased in rat granulosa cells. By contrast, gonadotropin withdrawal by metabolic clearance promoted LC3-II expression and decreased phosphorylation of AKT and S6K. In addition,in-vitroFSH treatment of rat granulosa cells also indicated inhibition of LC3-II expression accompanied by a marked increase in phosphorylation of AKT and S6K. Inhibition of AKT phosphorylation using AKT inhibitor VIII suppressed FSH-mediated phosphorylation of S6K, followed by an increase in LC3-II expression. Furthermore, co-treatment with FSH and AKT inhibitor increased the levels of apoptosis and cell death of granulosa cells compared with the single treatment with FSH. Taken together, our findings indicated that AKT-mediated activation of mTOR suppresses granulosa cell autophagy during follicular development and is involved in the regulation of apoptotic cell death.

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