Follicular somatic cell factors and follicle development

2011 ◽  
Vol 23 (1) ◽  
pp. 32 ◽  
Author(s):  
J. Buratini ◽  
C. A. Price
Keyword(s):  
Somatic Cell ◽  
Granulosa Cell ◽  
Bone Morphogenetic Proteins ◽  
Granulosa Cells ◽  
Primordial Follicle ◽  
Antral Follicle ◽  
Follicle Development ◽  
Follicle Growth ◽  
Theca Cells ◽  
Secreted Factors

Considerable attention is currently paid to oocyte-derived secreted factors that act upon cumulus and granulosa cells. Also important for follicle development are somatic cell-derived secreted factors. This is illustrated by the ability of granulosa cell-derived Kit ligand (KITL) to promote primordial follicle activation, and the loss of follicle development that accompanies KITL gene disruption. This review summarises our current understanding of somatic cell factors during both preantral and antral follicle growth, involving not only signalling from granulosa cells to the oocyte, but also signalling between granulosa and theca cells. Principal granulosa cell-derived factors include activin, anti-Müllerian hormone (AMH), bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs). Theca cells also secrete BMPs and FGFs. The interplay between these factors is equally important for follicle growth as the activity of oocyte-derived factors.

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.

scholarly journals Glial-derived neurotrophic factor promotes ovarian primordial follicle development and cell–cell interactions during folliculogenesis

Reproduction ◽  
2008 ◽  
Vol 135 (5) ◽  
pp. 671-682 ◽  
Author(s):  
Gretchen Dole ◽  
Eric E Nilsson ◽  
Michael K Skinner
Keyword(s):  
Microarray Analysis ◽  
Granulosa Cells ◽  
Neurotrophic Factor ◽  
Primordial Follicle ◽  
Cell Interactions ◽  
Follicle Development ◽  
Antral Follicles ◽  
Theca Cells ◽  
Oocyte Cytoplasm ◽  
Cell Cell

Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line-derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from 4-day-old female rat pups were maintained in organ culture for 10 days in the absence (control) or presence of GDNF or kit ligand (KL)/stem cell factor. Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor α1 (GFRα1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in the oocytes of antral follicles. GFRα1 was present in mural granulosa cells of antral follicles, theca cells, and ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell–cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells.

scholarly journals FSH Promotes Rat Follicle Development Through Inhibition of the Hippo Signalling Pathway

2021 ◽  
Author(s):  
Tairen Chen ◽  
Mengjing Wu ◽  
Yuting Dong ◽  
Bin Kong ◽  
Yufang Cai ◽  
...  
Keyword(s):  
Western Blot ◽  
In Vitro Culture ◽  
Granulosa Cells ◽  
Signalling Pathway ◽  
Control Group ◽  
Follicle Development ◽  
Follicle Growth ◽  
Expression Levels ◽  
Hippo Signalling

Abstract Purpose: Whether FSH promotes follicle growth by inhibiting the Hippo signalling pathway.METHODS: Ovaries were cultured in vitro into a control group (no intervention), an FSH group (0.3 IU/mL FSH), and a VP group (10 µg/mL vetiporfin). HE staining and follicle counts were performed at each stage after 3 hours of in vitro culture. Immunohistochemistry was performed to study the expression levels of LATS2, YAP, PLATS2, and PYAP, and their expression levels in each group were also analysed by Western blot.The number of secondary follicles was significantly increased in the FSH group, the arrangement of granulosa cells was neater, the nuclear fixation was reduced, and the number of atretic follicles was decreased in the VP group. The number of secondary follicles was significantly increased, the number of atretic follicles was reduced, and granulosa cell nuclear consolidation was reduced in the VP+FSH group. Immunohistochemistry showed that LATS2 and YAP expression levels were significantly increased and PLATS2 and PYAP expression levels were relatively decreased in the FSH group, PYAP and PLATS2 expression levels were significantly increased and YAP expression was significantly decreased in the VP group, and YAP and LATS2 expression levels were significantly increased and PYAP and PLATS2 expression levels were significantly decreased in the VP+FSH group. By Western blot, LATS2 and YAP were elevated and PYAP and PLAT2 were decreased in the FSH group, LATS2 and YAP were decreased and PYAP and PLATS were significantly elevated in the VP group, and LATS2 and YAP were elevated and PYAP and PLATS2 were decreased in the VP+FSH group.CONCLUSION: FSH promotes follicle development by inhibiting the Hippo signalling pathway.

scholarly journals Bone morphogenetic protein-6 enhances gonadotrophin-dependent progesterone and inhibin secretion and expression of mRNA transcripts encoding gonadotrophin receptors and inhibin/activin subunits in chicken granulosa cells

Reproduction ◽  
2007 ◽  
Vol 134 (2) ◽  
pp. 293-306 ◽  
Author(s):  
Sara L Al-Musawi ◽  
Richard T Gladwell ◽  
Philip G Knight
Keyword(s):  
Bone Morphogenetic Protein ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Function ◽  
Dependent Manner ◽  
Cell Type ◽  
Inhibin A ◽  
Theca Cells ◽  
Subunit Mrna ◽  
Morphogenetic Protein

The aims were to examine ovarian expression of bone morphogenetic protein (BMP) ligands/receptor mRNAs in the chicken and to test the hypothesis that theca-derived BMP(s) modulates granulosa cell function in a paracrine manner. RT-PCR revealed expression of multiple BMPs in granulosa and theca cells from prehierarchical and preovulatory follicles with greater expression in theca cells; both cell types expressed BMP receptors-IA, -IB and -II consistent with tissue responsiveness. Preovulatory granulosa cells (F1, F2 and F3/4) were cultured with BMP-6 (expressed by theca but not granulosa) in the presence/absence of LH, FSH or 8-Br-cAMP. BMP-6 increased ‘basal’ and gonadotrophin-induced inhibin-A and progesterone secretion by each cell type but did not enhance the effect of 8-Br-cAMP. This indicates that the observed synergism between BMP-6 and gonadotrophin might involve BMP-induced up-regulation of gonadotrophin receptors. In support of this, BMP-6 alone increased LH-receptor (LHR) mRNA in F1 cells and FSH-receptor (FSHR) mRNA in F1, F2 and F3/4 cells. BMP-6 also enhanced LH/FSH-induced LHR transcript amount in each cell type but did not raise FSHR transcript amounts above those induced by BMP-6 alone. To further explore BMP-6 action on inhibin-A secretion, we quantified inhibin/activin subunits (α, βA, βB) mRNAs. Consistent with its effect on inhibin-A secretion, BMP-6 enhanced ‘basal’ expression of α- and βA-subunit mRNA in F1, F2 and F3/4 cells, and βB-subunit mRNA in F3/4 cells. BMP-6 markedly enhanced FSH/LH-induced expression of α-subunit in all follicles and FSH-induced βA-subunit in F2 and F3/4 follicles but not in F1 follicles. Neither BMP-6 alone, nor FSH/LH alone, affected ‘basal’ βB mRNA abundance. However, co-treatment with gonadotrophin and BMP-6 greatly increased βB-subunit expression, the response being lowest in F1 follicles and greatest in F3/4 follicles. Collectively, these results support the hypothesis that intraovarian BMPs of thecal origin have a paracrine role in modulating granulosa cell function in the chicken in a preovulatory stage-dependent manner.

Follistatin but not α or βA inhibin subunit mRNA is expressed in ovine fetal ovaries in late gestation

1994 ◽  
Vol 13 (1) ◽  
pp. 1-9 ◽  
Author(s):  
R Braw-Tal ◽  
D J Tisdall ◽  
N L Hudson ◽  
P Smith ◽  
K P McNatty
Keyword(s):  
Mrna Expression ◽  
Granulosa Cells ◽  
Cell Function ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Late Gestation ◽  
Follicle Growth ◽  
Primordial Follicles ◽  
Fetal Ovary ◽  
Ovine Fetal

ABSTRACT The aim of this study was to investigate the sites of follistatin and α and βA inhibin mRNA expression in the ovaries of female sheep fetuses at 90, 100, 120 and 135 days of gestation (term=day 147). At 90 and 100 days primordial follicles were formed, followed by the appearance of primary follicles at 100 days of gestation. At days 120 and 135, primordial, primary and preantral (i.e. secondary) follicles were present in the ovaries, but antral (i.e. tertiary) follicles were not observed at any of these gestational ages. Two Booroola genotypes were studied: homozygous carriers (BB) and non-carriers (++) of the fecundity gene (FecB). Irrespective of genotype no specific hybridization of the α and βA inhibin riboprobes was detected in any ovarian cells at days 90, 100, 120 or 135 of gestation. In control mature ovaries, on the other hand, strong hybridization in the granulosa cells of antral follicles was observed. In contrast to α and βA inhibin, follistatin antisense (but not sense) riboprobes hybridized specifically to the granulosa cells of preantral follicles with two or more layers of cells at days 120 and 135 of gestation. Moreover, hybridization was also evident in the cells of the ovarian rete at days 120 and 135, but not at 90 or 100 days. No follistatin mRNA expression was observed in the granulosa cells of primordial or primary follicles or in any other ovarian cell type at any of the gestational ages examined. No FecB-specific differences in follistatin expression were noted with respect to stage of preantral follicular development and there were no obvious differences in the intensity of expression. These results show that follistatin mRNA is expressed specifically in the granulosa cells and intraovarian rete. Expression of follistatin in rete cells was coincident with the increasing numbers of growing follicles within the fetal ovary, indicating that rete cell function may have a role in the ontogeny of early follicular growth. Our results suggest that follistatin and α and βA inhibin may not be important for the initiation of follicle growth in the sheep ovary, since these genes are not expressed during the transformation of a primordial follicle to a primary structure. However, the evidence for follistatin mRNA expression in the ovine fetal ovary implies that this hormone is likely to play a role during the early stages of follicle growth.

scholarly journals The Phytoestrogen Quercetin Impairs Steroidogenesis and Angiogenesis in Swine Granulosa Cells In Vitro

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Sujen Eleonora Santini ◽  
Giuseppina Basini ◽  
Simona Bussolati ◽  
Francesca Grasselli
Keyword(s):  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Redox Status ◽  
Negative Influence ◽  
Animal Nutrition ◽  
Follicle Development ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Experimental evidence documents that nutritional phytoestrogens may interact with reproductive functions but the exact mechanism of action is still controversial. Since quercetin is one of the main flavonoids in livestock nutrition, we evaluated its possible effects on cultured swine granulosa cell proliferation, steroidogenesis, and redox status. Moreover, since angiogenesis is essential for follicle development, the effect of the flavonoid on Vascular Endothelial Growth Factor output by granulosa cells was also taken into account. Our data evidence that quercetin does not affect granulosa cell growth while it inhibits progesterone production and modifies estradiol production in a dose-related manner. Additionally, the flavonoid interferes with the angiogenic process by inhibiting VEGF production as well as by altering redox status. Since steroidogenesis and angiogenesis are strictly involved in follicular development, these findings appear particularly relevant, pointing out a possible negative influence of quercetin on ovarian physiology. Therefore, the possible reproductive impact of the flavonoid should be carefully considered in animal nutrition.

scholarly journals Gene expression patterns in granulosa cells and oocytes at various stages of follicle development as well as in in vitro grown oocyte-and-granulosa cell complexes

2016 ◽  
Vol 62 (4) ◽  
pp. 359-366 ◽  
Author(s):  
Yasuhisa MUNAKATA ◽  
Ryoka KAWAHARA-MIKI ◽  
Shogo SHIRATSUKI ◽  
Hidetaka TASAKI ◽  
Nobuhiko ITAMI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Follicle Development ◽  
Cell Complexes

scholarly journals Cytokine (IL16) and tyrphostin actions on ovarian primordial follicle development

Reproduction ◽  
2014 ◽  
Vol 148 (3) ◽  
pp. 321-331 ◽  
Author(s):  
Amanda Feeney ◽  
Eric Nilsson ◽  
Michael K Skinner
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Ovarian Follicle ◽  
Primordial Follicle ◽  
Cytokine Signaling ◽  
Follicle Development ◽  
Primary Follicle ◽  
Primordial Follicles ◽  
Network Analyses

An ovarian follicle is composed of an oocyte and surrounding theca and granulosa cells. Oocytes are stored in an arrested state within primordial follicles until they are signaled to re-initiate development by undergoing primordial-to-primary follicle transition. Previous gene bionetwork analyses of primordial follicle development identified a number of critical cytokine signaling pathways and genes potentially involved in the process. In the current study, candidate regulatory genes and pathways from the gene network analyses were tested for their effects on the formation of primordial follicles (follicle assembly) and on primordial follicle transition using whole ovary organ culture experiments. Observations indicate that the tyrphostin inhibitor (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one increased follicle assembly significantly, supporting a role for the MAPK signaling pathway in follicle assembly. The cytokine interleukin 16 (IL16) promotes primordial-to-primary follicle transition as compared with the controls, where as Delta-like ligand 4 (DLL4) and WNT-3A treatments have no effect. Immunohistochemical experiments demonstrated the localization of both the cytokine IL16 and its receptor CD4 in the granulosa cells surrounding each oocyte within the ovarian follicle. The tyrphostin LDN193189 (LDN) is an inhibitor of the bone morphogenic protein receptor 1 within the TGFB signaling pathway and was found to promote the primordial-to-primary follicle transition. Observations support the importance of cytokines (i.e., IL16) and cytokine signaling pathways in the regulation of early follicle development. Insights into regulatory factors affecting early primordial follicle development are provided that may associate with ovarian disease and translate to improved therapy in the future.

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