scholarly journals The intraovarian cellular origins of GDF9 and BMP15 in the mouse and aspects of their biological properties

2021 ◽  
Author(s):  
◽  
Brigitta Mester
Keyword(s):  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Cumulus Cell ◽  
Follicular Development ◽  
Precursor Protein ◽  
Biologically Active ◽  
Activation Process ◽  
Follicular Cells ◽  
Lh Surge ◽  
Secondary Stage

<p>Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are both members of the TGF-ß protein superfamily and are known to be essential for normal follicular development in mammals. Several studies have highlighted the species-specific effects of BMP15 and GDF9, which could be attributed, at least in part to the differences in the follicular expression patterns and to different forms of the secreted proteins. In the mouse, GDF9 is required for follicular development, whereas BMP15 appears to be only required near ovulation with contradictory reports as to the timing of BMP15 expression. However, mouse BMP15 and GDF9 are known to have the capability of acting together synergistically. The aims of this thesis were to characterise in the mouse ovary, the expression patterns (localisation and levels) of Bmp15 and Gdf9 mRNA throughout follicular development, and to determine the peri-ovulatory expression of the corresponding proteins.  In situ hybridisation and quantitative PCR analyses of ovarian samples and follicular cells collected from control and superovulated mice confirmed that Gdf9 and Bmp15 mRNA are expressed exclusively in oocytes from primary and early secondary stage follicles respectively. qPCR analysis of denuded oocytes (DO) revealed a tight correlation, and therefore co-regulation, between the expression levels of Bmp15 and Gdf9 irrespective of follicular developmental stage, with steady expression until the preovulatory LH surge when down-regulation of Bmp15 and Gdf9 occurred. Throughout the follicular developmental stages examined, Gdf9 was expressed in greater abundance relative to Bmp15, with a Bmp15:Gdf9 mRNA ratio of 1:4.12.  [...] In conclusion, oocyte-derived Bmp15 and Gdf9 mRNA expression is co-regulated throughout follicular development in mice, with Gdf9 being more abundant than Bmp15, which might be an important factor in determining high ovulation quota. The expression of the target genes is down-regulated as the oocyte reaches developmental competence following the preovulatory LH surge. Protein expression data provided evidence that in vivo the immature mouse oocyte is capable of secreting all BMP15 protein forms previously detected in vitro. After the preovulatory LH surge, all visible protein forms are associated with the somatic follicular cells, in particular with the expanded cumulus mass. Of particular interest is the presence of the large protein complexes in the cumulus cell lysates, which suggests a storage and activation process involving ECM proteins, similar to the mechanism reported for other TGF-ß superfamily members, such as TGF-ß1 and myostatin.  The finding that the BMP15 precursor protein is biologically active with a different activity to that of the processed mature protein form suggests that the full-length precursor protein may regulate or provide at least a portion of the biological activity of BMP15 in mice.</p>

scholarly journals The intraovarian cellular origins of GDF9 and BMP15 in the mouse and aspects of their biological properties

2021 ◽  
Author(s):  
◽  
Brigitta Mester
Keyword(s):  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Cumulus Cell ◽  
Follicular Development ◽  
Precursor Protein ◽  
Biologically Active ◽  
Activation Process ◽  
Follicular Cells ◽  
Lh Surge ◽  
Secondary Stage

<p>Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are both members of the TGF-ß protein superfamily and are known to be essential for normal follicular development in mammals. Several studies have highlighted the species-specific effects of BMP15 and GDF9, which could be attributed, at least in part to the differences in the follicular expression patterns and to different forms of the secreted proteins. In the mouse, GDF9 is required for follicular development, whereas BMP15 appears to be only required near ovulation with contradictory reports as to the timing of BMP15 expression. However, mouse BMP15 and GDF9 are known to have the capability of acting together synergistically. The aims of this thesis were to characterise in the mouse ovary, the expression patterns (localisation and levels) of Bmp15 and Gdf9 mRNA throughout follicular development, and to determine the peri-ovulatory expression of the corresponding proteins.  In situ hybridisation and quantitative PCR analyses of ovarian samples and follicular cells collected from control and superovulated mice confirmed that Gdf9 and Bmp15 mRNA are expressed exclusively in oocytes from primary and early secondary stage follicles respectively. qPCR analysis of denuded oocytes (DO) revealed a tight correlation, and therefore co-regulation, between the expression levels of Bmp15 and Gdf9 irrespective of follicular developmental stage, with steady expression until the preovulatory LH surge when down-regulation of Bmp15 and Gdf9 occurred. Throughout the follicular developmental stages examined, Gdf9 was expressed in greater abundance relative to Bmp15, with a Bmp15:Gdf9 mRNA ratio of 1:4.12.  [...] In conclusion, oocyte-derived Bmp15 and Gdf9 mRNA expression is co-regulated throughout follicular development in mice, with Gdf9 being more abundant than Bmp15, which might be an important factor in determining high ovulation quota. The expression of the target genes is down-regulated as the oocyte reaches developmental competence following the preovulatory LH surge. Protein expression data provided evidence that in vivo the immature mouse oocyte is capable of secreting all BMP15 protein forms previously detected in vitro. After the preovulatory LH surge, all visible protein forms are associated with the somatic follicular cells, in particular with the expanded cumulus mass. Of particular interest is the presence of the large protein complexes in the cumulus cell lysates, which suggests a storage and activation process involving ECM proteins, similar to the mechanism reported for other TGF-ß superfamily members, such as TGF-ß1 and myostatin.  The finding that the BMP15 precursor protein is biologically active with a different activity to that of the processed mature protein form suggests that the full-length precursor protein may regulate or provide at least a portion of the biological activity of BMP15 in mice.</p>

scholarly journals Photoperiod-dependent modulation of anti-Müllerian hormone in female Siberian hamsters, Phodopus sungorus

Reproduction ◽  
2008 ◽  
Vol 135 (3) ◽  
pp. 335-342 ◽  
Author(s):  
Esther W Kabithe ◽  
Ned J Place
Keyword(s):  
Granulosa Cells ◽  
Expression Patterns ◽  
Follicular Development ◽  
Day Length ◽  
Phodopus Sungorus ◽  
Reproductive Aging ◽  
Primordial Follicles ◽  
Short Day ◽  
Siberian Hamsters ◽  
Secondary Stage

Fertility and fecundity decline with advancing age in female mammals, but reproductive aging was decelerated in Siberian hamsters (Phodopus sungorus) raised in a short-day (SD) photoperiod. Litter success was significantly improved in older hamsters when reared in SD and the number of primordial follicles was twice that of females held in long days (LD). Because anti-Müllerian hormone (AMH) appears to inhibit the recruitment of primordial follicles in mice, we sought to determine whether the expression patterns of AMH differ in the ovaries and serum of hamsters raised in SD versus LD. Ovaries of SD female hamsters are characterized by a paucity of follicular development beyond the secondary stage and are endowed with an abundance of large eosinophilic cells, which may derive from granulosa cells of oocyte-depleted follicles. In ovaries from 10-week-old SD hamsters, we found that the so-called ‘hypertrophied granulosa cells’ were immunoreactive for AMH, as were granulosa cells within healthy-appearing primary and secondary follicles. Conversely, ovaries from age-matched LD animals lack the highly eosinophilic cells present in SD ovaries. Therefore, AMH staining in LD was limited to primary and secondary follicles that are comparable in number to those found in SD ovaries. The substantially greater AMH expression in SD ovaries probably reflects the abundance of hypertrophied granulosa cells in SD ovaries and their relative absence in LD ovaries. The modulation of ovarian AMH by day length is a strong mechanistic candidate for the preservation of primordial follicles in female hamsters raised in a SD photoperiod.

116 Differential expression of connexin 43 and 37 mRNA transcripts during the estrous cycle in canines

2019 ◽  
Vol 31 (1) ◽  
pp. 184
Author(s):  
M. De los Reyes ◽  
J. Palomino ◽  
R. Espinoza ◽  
C. Gallego
Keyword(s):  
Gene Expression ◽  
Gap Junctions ◽  
Corpus Luteum ◽  
Connexin 43 ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Follicular Development ◽  
Oestrous Cycle ◽  
Mrna Levels ◽  
Follicular Cells

Gap junctions are intercellular channels that mediate cell-to-cell communication, allowing the passage of small signalling molecules. In the ovary, connexin 43 (Cx43) and connexin 37 (Cx37) are important gap junctional proteins expressed in the granulosa and cumulus cells or oocytes of several species. Gap junctions and connexins are required for the regulation of the oocytes meiotic resumption in preovulatory follicles after the surge of LH. However, unlike other species, canine oocytes do not resume meiosis before ovulation, which could be related to expression patterns of Cx43 and Cx37 during oocyte development and ovulation. Therefore, this study aimed to address the canine Cx37 and Cx43 gene expressions throughout the oestrous cycle, including the preovulatory period. The ovaries were obtained from bitches 1-6 years old (n=72) following ovariohysterectomy. The stage of the oestrous cycle was assessed according the ovarian structures and by measurements of serum progesterone (P4) levels obtained from blood samples on the day of surgery. Anestrus was &lt;0.1 ng/mL P4 and absence of follicles or corpus luteum in the ovarian surface; proestrus was 0.2-2 ng/mL P4 and growing small to medium follicles on the surface of the ovaries; oestrus was 2-19 mg/mL P4 and large follicles on the surface of the ovaries; and diestrus was &gt;20 ng/mL P4 and mainly predominant corpus luteum on the ovaries. For Cx43 analysis, follicular cells (granulosa and theca) were mechanically recovered from follicles (n=620) distributed into 4 types: prenatal (1 layer of granulosa cells up to the onset of antrum formation), small antral (~0.2-0.39mm), medium antral (~0.4-5.9mm), and large antral (~6-10mm). For Cx37 study, the cumulus-oocytes complexes (COC) from the same follicles were used. Total RNA extraction was performed, and the evaluation of gene expression levels was achieved by relative quantification quantitative PCR analysis in follicular cells and COC. The data from at least 3 independent experiments for each gene were evaluated by ANOVA. The gene expression of both Connexins were observed in all stages of follicular development; however, the mRNA levels varied over the oestrous cycle. Both Cx43 and Cx37 transcripts showed the highest (P&lt;0.05) levels at anestrus when compared to other phases. The mRNA levels of both genes remained without changes in large follicles at oestrus stage, suggesting that, in contrast to other mammals where LH down-regulates connexins expression leading to the subsequent loss of intercellular coupling, the communication between the oocyte and follicular cells was maintained in canines. In conclusion, these 2 connexin genes were differentially expressed in canine follicular cells and COC during the follicular development. The maintenance of the gene expression of these connexins at the final follicular growth may be involved in the prolonged meiotic arrest in this species. Supported by Ga grant from FONDECYT (1171670).

scholarly journals Expression patterns of signalling molecules and transcription factors in the early rabbit embryo and their significance for modelling amniote axis formation

2021 ◽  
Author(s):  
Ruben Plöger ◽  
Christoph Viebahn
Keyword(s):  
Transcription Factors ◽  
Expression Patterns ◽  
In Situ Hybridisation ◽  
Body Plan ◽  
The Body ◽  
Anchor Point ◽  
Axis Formation ◽  
Point Model ◽  
Signalling Molecules ◽  
Rabbit Embryo

AbstractThe anterior-posterior axis is a central element of the body plan and, during amniote gastrulation, forms through several transient domains with specific morphogenetic activities. In the chick, experimentally proven activity of signalling molecules and transcription factors lead to the concept of a ‘global positioning system’ for initial axis formation whereas in the (mammotypical) rabbit embryo, a series of morphological or molecular domains are part of a putative ‘three-anchor-point model’. Because circular expression patterns of genes involved in axis formation exist in both amniote groups prior to, and during, gastrulation and may thus be suited to reconcile these models, the expression patterns of selected genes known in the chick, namely the ones coding for the transcription factors eomes and tbx6, the signalling molecule wnt3 and the wnt inhibitor pkdcc, were analysed in the rabbit embryonic disc using in situ hybridisation and placing emphasis on their germ layer location. Peripheral wnt3 and eomes expression in all layers is found initially to be complementary to central pkdcc expression in the hypoblast during early axis formation. Pkdcc then appears — together with a posterior-anterior gradient in wnt3 and eomes domains — in the epiblast posteriorly before the emerging primitive streak is marked by pkdcc and tbx6 at its anterior and posterior extremities, respectively. Conserved circular expression patterns deduced from some of this data may point to shared mechanisms in amniote axis formation while the reshaping of localised gene expression patterns is discussed as part of the ‘three-anchor-point model’ for establishing the mammalian body plan.

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 Large-Scale Metadata Analysis of Ovary Based Multi-Omics Datasets for Understanding the Genes Regulating Litter Size

2020 ◽  
Author(s):  
Ayyappa Kumar Sista Kameshwar ◽  
Julang Li
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Litter Size ◽  
Large Scale ◽  
Expression Patterns ◽  
Genetic Selection ◽  
Follicular Development ◽  
Oocyte Quality ◽  
Differentially Expressed ◽  
Metadata Analysis

Abstract Background : Litter size is a very important production index in the livestock industry, which is controlled by various complex physiological processes. To understand and reveal the common gene expression patterns involved in controlling prolificacy, we have performed a large-scale metadata analysis of five genome-wide transcriptome datasets of pig and sheep ovary samples obtained from high and low litter groups, respectively. We analyzed separately each transcriptome dataset using GeneSpring v14.8 software by implementing standard, generic analysis pipelines and further compared the list of most significant and differentially expressed genes obtained from each dataset to identify genes that are found to be common and significant across all the studies. Results : We have observed a total of 62 differentially expressed genes common among more than two gene expression datasets. The KEGG pathway analysis of most significant genes has shown that they are involved in metabolism, the biosynthesis of lipids, cholesterol and steroid hormones, immune system, cell growth and death, cancer-related pathways and signal transduction pathways. Of these 62 genes, we further narrowed the list to the 25 most significant genes by focusing on the ones with fold change >1.5 and p<0.05. These genes are CYP11A1, HSD17B2, STAR, SCARB1, IGSF8, MSMB, SERPINA1 , FAM46C, HEXA, PTTG1, TIMP1, FAM167B, CCNG1, FAXDC2, HMGCS1, L2HGDH, Lipin1, MME, MSMO1, PARM1, PTGFR, SLC22A4, SLC35F5, CCNA2, CENPU, CEP55, RASSF2, and SLC16A3 . Conclusions : Interestingly, comparing the list of genes with the list of genes obtained from our literature search analysis, we found only three genes in common. These genes are HEXA, PTTG1, and TIMP1. Our finding points to the potential of a few genes that may be important for ovarian follicular development and oocyte quality. Future studies revealing the function of these genes will further our understanding of how litter size is controlled in the ovary while also providing insight on genetic selection of high litter gilts.

scholarly journals Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1618
Author(s):  
Kristina Kiisholts ◽  
Kaido Kurrikoff ◽  
Piret Arukuusk ◽  
Ly Porosk ◽  
Maire Peters ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cellular Proliferation ◽  
Expression Patterns ◽  
In Vitro Models ◽  
Cell Penetrating Peptides ◽  
Biologically Active ◽  
Therapeutic Effects ◽  
Cell Penetrating ◽  
Proliferation And Invasion

Gene therapy is a powerful tool for the development of new treatment strategies for various conditions, by aiming to transport biologically active nucleic acids into diseased cells. To achieve that goal, we used highly potential delivery vectors, cell-penetrating peptides (CPPs), as oligonucleotide carriers for the development of a therapeutic approach for endometriosis and cancer. Despite marked differences, both of these conditions still exhibit similarities, like excessive, uncoordinated, and autonomous cellular proliferation and invasion, accompanied by overlapping gene expression patterns. Thus, in the current study, we investigated the therapeutic effects of CPP and siRNA nanoparticles using in vitro models of benign endometriosis and malignant glioblastoma. We demonstrated that CPPs PepFect6 and NickFect70 are highly effective in transfecting cell lines, primary cell cultures, and three-dimensional spheroids. CPP nanoparticles are capable of inducing siRNA-specific knockdown of therapeutic genes, ribonucleotide reductase subunit M2 (RRM2), and vascular endothelial growth factor (VEGF), which results in the reduction of in vitro cellular proliferation, invasion, and migration. In addition, we proved that it is possible to achieve synergistic suppression of endometriosis cellular proliferation and invasion by combining gene therapy and hormonal treatment approaches by co-administering CPP/siRNA nanoparticles together with the endometriosis-drug danazol. We suggest a novel target, RRM2, for endometriosis therapy and as a proof-of-concept, we propose a CPP-mediated gene therapy approach for endometriosis and cancer.

scholarly journals Gene expression of growth factor BMP15, GDF9, FGF2 and their receptors in bovine follicular cells

2018 ◽  
pp. 6778-6787 ◽  
Author(s):  
Pablo S Reineri ◽  
María S. Coria ◽  
María G. Barrionuevo ◽  
Olegario Hernández ◽  
Santiago Callejas ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Follicular Development ◽  
Fibroblast Growth ◽  
Rt Pcr ◽  
Follicular Cells

Introduction. Growth and follicular maturation involve transformations of various components of the follicle, such as the oocyte, granulosa and techa cells. Several growth factors, including differentiation growth factor 9 (GDF9), bone morphogenic protein 15 (BMP15) and basic fibroblast growth factor (FGF2) are important for follicular development and oocyte maturation, by its ability to increase the proliferation of granulosa, techa cells and the ovarian stroma. Objetive. Evaluate mRNA expression of GDF9, BMP15, FGF2 and their main receptors, transforming growth factor beta receptor 1 (TGFβ-R1), bone morphogenetic protein receptor, type IB (BMPR-IB) and fibroblast growth factor receptor 2 (FGFR2) in bovine follicular cells. Materials and methods. Total RNA was isolated from pooled samples of oocytes (OOs), cumulus cells (CCs) of cumulus oocyte complexes (COCs) and follicular cell pellets (PCs) of 70 ovaries obtained from 96 beef heifers, collected at a local abattoir. The expression pattern of growth factors and their receptors in follicular bovine cells was evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). Results. The mRNA transcripts encoding GDF9, BMP15, FGF2, TGFβ-R1, BMPR-IB and FGFR2 genes were detected, by RT-PCR, in all studied cells. This is the first time that the expression of TGFβ-R1 and BMPR-IB receptors is reported in bovine oocytes. Conclusions. The presence of growth factors and receptor transcripts in the studied cells indicate that these factors could act as paracrine and autocrine regulators of folliculogenesis.

188 IMPROVEMENT OF IN VITRO CANINE OOCYTE MATURATION BY OVIDUCTAL SECRETOME

2017 ◽  
Vol 29 (1) ◽  
pp. 202 ◽  
Author(s):  
A. Lange-Consiglio ◽  
C. Perrini ◽  
P. Esposti ◽  
F. Cremonesi
Keyword(s):  
Oocyte Maturation ◽  
In Vitro Maturation ◽  
Cumulus Cell ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Chi Square ◽  
Cell Layers ◽  
Hoechst Staining

The in vitro maturation of canine oocyte is problematic because it is difficult to reproduce the oviducal microenvironment where the in vivo maturation occurs. Because cells are able to communicate with each other by paracrine action, oviducal cells could be in vitro cultivated to obtain the conditioned medium (CM) consisting of soluble factors and microvesicles (MV), which represent a carrier for nonsoluble molecules including microRNA. The aim of the present work was to investigate the effect of the addition of CM or MV, secreted by oviducal cells, to the canine in vitro maturation medium. To generate CM, cells from oviducts of 3 animals in late oestrus were cultured for 5 days at 38.5°C in a humidified atmosphere of 5% CO2. Supernatants were collected, pooled, centrifuged at 2500 × g, and stored at −80°C. Microvesicles were obtained by ultracentrifugation of CM at 100,000 × g for 1 h at 4°C and measured for concentration and size by a Nanosight instrument. Ovaries were obtained from 50 healthy domestic bitches (1–4 years old) of different breeds that underwent ovariectomy regardless of the oestrous cycle. Cumulus-oocyte complexes were released by slicing the ovarian cortex with a scalpel blade, and only Grade 1 cumulus-oocyte complexes (darkly granulated cytoplasm and surrounded by 3 or more compact cumulus cell layers) 110 to 120 µm in diameter were selected for culture. Maturation was performed at 38.5°C in a humidified atmosphere of 5% CO2 and 5% of O2 in bi-phasic systems: 24 h in SOF with 5.0 μg mL−1 of LH followed by 48 h in SOF supplemented with 10% of oestrous bitch serum and 10% CM or 50, 75, 100, or 150 × 106 MV mL−1 labelled with PKH-26. Control was the same medium without CM or MV. Oocytes were observed under a fluorescent microscope to detect metaphase II (MII), by Hoechst staining, and the incorporation of MV. Statistical analysis was performed by chi-square test. Results show that canine oviducal cells secreted MV of 234 ± 23 nm in size, underling that these MV fall within the shedding vesicles category. The incorporation of labelled MV occurred at first in cumulus cells, at 48 h of maturation, and then, at 72 h, in oocyte cytoplasm. These MV had a positive effect on maturation rate (MII) at the concentration of 75 and 100 × 106 MV mL−1 compared with CM and control (20.34 and 21.82 v. 9.09 and 3.95%, respectively). The concentration of 150 × 106 MV mL−1 provided only 9.26% of MII. To understand the role of MV, we assessed the expression of 3 microRNA (miRNA-30b, miR-375, and miR-503) that are involved in some key pathways (WNT, MAPK, ERbB, and TGFβ) regulating follicular development and meiotic resumption. The lower rate of MII with the higher concentration of MV is possibly due to the high level of miR-375, which recent literature shows to suppress the TGFβ pathway, leading to impaired oocyte maturation. In conclusion, the oviducal MV, or specific microRNA, are involved in cellular trafficking during oocyte maturation, and their possible use in vitro could facilitate the exploitation of canine reproductive biotechnologies.

037. IMMUNE-LIKE MECHANISMS ASSOCIATED WITH OVULATION

2009 ◽  
Vol 21 (9) ◽  
pp. 10
Author(s):  
J. Richards
Keyword(s):  
Granulosa Cells ◽  
Immune Cell ◽  
Expression Patterns ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Mature Oocyte ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Oocyte Meiosis ◽  
Mitogen Activated Protein

Ovulation is the unique biological process by which a mature oocyte and surrounding somatic cells, the cumulus cell-oocyte complex (COC), are released from the surface of the ovary into the oviduct for transport and fertilization. Ovulation is similar to an inflammatory response: the follicles become hyperemic, produce prostaglandins and synthesize a hyaluronan-rich extracellular matrix. However, this view of ovulation may be too restrictive and need to be broadened to encompass the innate immune cell surveillance response system. This hypothesis is being proposed because ovarian granulosa cells and cumulus cells express and respond to innate immune cell related surveillance proteins (Toll-like receptors 2 and 4) and cytokines such as interleukin 6 (IL6) during ovulation. In addition, recent studies indicate that the ovulation process that is set in motion by the surge of luteinizing hormone (LH) is mediated, in large part, by the EGF-like factors (Amphiregulin, epiregulin and betacellulin) and their critical activation of RAS, most probably KRAS that is expressed at high levels in granulosa cells, and the mitogen activated protein kinases, MAP3/1 (ERK1/2). Mice in which granulosa cells are depleted of ERK1/2 fail to ovulate, oocyte meiosis does not resume, COC expansion is impaired and luteinization is blocked. Thus the global molecular reprogramming of granulosa cell gene expression patterns is completely derailed. Supported, in part by NIH-HD-16229, -16272 and -07495 (SCCPIR).

Sign in / Sign up

Export Citation Format

Share Document