Overexpression of ribosomal RNA in cumulus cells of patients with polycystic ovary syndrome

Polzikov, M. A.; Yakovenko, S.A.; Voznesenskaya, J.V.; Troshina, M.N.; Зацепина, О. В.

doi:10.1007/s10815-012-9827-6

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…The GSEA s howed up-regulation of pathways involved in cell cycle and DNA replication in PCOS CRCs. This is in line with previous studies showing hyperproliferative cumulus [ 7 ] and granulosa [ 3 ] cells in PCOS. The LH/hCG surge for final oocyte maturation dramatically down-regulate cell cycle genes in human granulosa cells [ 37 ] as well as in rodent cumulus-oocyte-complexes [ 38 ].…”

Section: Discussionsupporting

confidence: 93%

“…Previous studies of PCOS women compared to healthy women revealed gene expression differences in metaphase ІІ (MII) oocytes [ 4 ], in cumulus cells of individual MІІ oocytes with unknown developmental potential [ 5 ] and pooled, cultured cumulus cells [ 6 ]. Ribosomal RNA content was increased in cumulus cells of PCOS women [ 7 ], which could indicate a higher rate of proliferation; also granulosa cells from PCOS women have been shown to be hyperproliferative [ 3 ]. These alterations may suggest an altered oocyte quality in PCOS patients compared to controls.…”

Section: Introductionmentioning

confidence: 99%

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The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

et al. 2014

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BackgroundCorona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls.MethodsAll patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays.ResultsThe transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5).ConclusionThe overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

et al. 2014

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“…It is well-known that ribosome biogenesis deficiency often leads to an impairment in cell growth and to cell death while elevated ribosomal function results in increased cell cycle progression and proliferation[33]. Thus, it is possible that the increased ribosomal content and presumably elevated translation that were found in bad quality eggs may reflect dysregulated cell cycle progression and cell growth, which in fact may lead to premature cell death as shown by pathological models in which loss of cell cycle and cell death regulators lead to disease[34,35]. On the other hand, it is also a possibility that ribosome biogenesis dysregulation may be an effect and not cause of loss of embryonic survival; an unknown mechanism that operates during oogenesis may cause the accumulation of ribosomal content in bad quality eggs and its abundance reflects a dysfunction of the mechanism.…”

Section: Discussionmentioning

confidence: 99%

Lost in translation: egg transcriptome reveals molecular signature to predict developmental success and novel maternal-effect genes

Cheung

Tri

Cam

et al. 2018

Preprint

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BackgroundGood quality or developmentally competent eggs result in high survival of progeny. Previous research has shed light on factors that determine egg quality, however, large gaps remain. Initial development of the embryo relies on maternally-inherited molecules, such as transcripts, deposited in the egg, thus, they would likely reflect egg quality. We performed transcriptome analysis on zebrafish fertilized eggs of different quality from unrelated, wildtype couples to obtain a global portrait of the egg transcriptome to determine its association with developmental competence and to identify new candidate maternal-effect genes.ResultsFifteen of the most differentially expressed genes (DEGs) were validated by quantitative real-time PCR. Gene ontology analysis showed that enriched terms included ribosomes and translation. In addition, statistical modeling using partial least squares regression and genetics algorithm also demonstrated that gene signatures from the transcriptomic data can be used to predict reproductive success. Among the validated DEGs, otulina and slc29a1a were found to be increased in good quality eggs and to be predominantly localized in the ovaries. CRISPR/Cas9 knockout mutants of each gene revealed remarkable subfertility whereby the majority of their embryos were unfertilizable. The Wnt pathway appeared to be dysregulated in the otulina knockout-derived eggs.ConclusionsOur novel findings suggested that even in varying quality of eggs due to heterogeneous causes from unrelated wildtype couples, gene signatures exist in the egg transcriptome, which can be used to predict developmental competence. Further, transcriptomic profiling revealed two new potential maternal-effect genes that have essential roles in vertebrate reproduction.

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“…Granulosa cells are divided into two types: mural granulosa cells (MGC) and cumulus cells. Cumulus cells are specialized cells that are actually derived from the granulosa cells that surround and nourish the oocyte during maturation [17]. Cumulus cell apoptosis plays a critical role in the growth and development of the oocyte.…”

Section: Discussionmentioning

confidence: 99%

BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries

Zhai

Liu

et al. 2013

Cell Physiol Biochem

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Background: Bone morphogenetic protein-15 (BMP15) is a maternal gene necessary for mammalian reproduction. BMP15 expression increased in oocytes accompanied by follicle growth and development. The function and regulation mechanism of BMP15 in porcine cumulus cell apoptosis process is still unclear now. Methods: In this study, flow cytometry (FCM) was used to analyze the effects of BMP15 with different concentrations to cumulus cell apoptosis. High-throughput sequencing technology was carried out to screen regulatory genes linked closely with BMP15. In order to confirm the function of (MCP-1)/CCL2 and FBN1 in cumulus cell apoptosis, RNA interference (RNAi) method was used to inhibit the expression of (MCP-1)/CCL2 and FBN1. Apoptosis and proliferation of cumulus cell treated with siRNA transfection technology were measured by FCM, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, quantitative real time-PCR (RT-qPCR) and western blotting. Results: The results showed that the apoptosis levels of cumulus cell treated by BMP15 decreased significantly in a dose-dependent manner. The expression of related genes protein 1 (MCP-1)/CCL2 and fibrillin1 (FBN1) were both regulated by BMP15. After transfection, the proliferation of porcine cumulus cells increased significantly and apoptosis of cumulus cells was prevented while FBN1 was silenced after BMP15 treatment. The proliferation of cumulus cells decreased significantly and apoptosis rate of cumulus cells increased significantly while CCL2 was silenced. Conclusion: The results obtained in this study firstly demonstrated that CCL2 and FBN1 are important regulatory factors of BMP15 in preventing cumulus cell apoptosis in porcine ovaries.

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Overexpression of ribosomal RNA in cumulus cells of patients with polycystic ovary syndrome

Cited by 8 publications

References 12 publications

The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

The transcriptome of corona radiata cells from individual MІІ oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

Lost in translation: egg transcriptome reveals molecular signature to predict developmental success and novel maternal-effect genes

BMP15 Prevents Cumulus Cell Apoptosis Through CCL2 and FBN1 in Porcine Ovaries

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