Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling

May‐Panloup, Pascale; Ferré-L’Hôtellier, Véronique; Morinière, Catherine; Marcaillou, Charles; Lemerle, S.; Malinge, Marie‐Claire; Coutolleau, Anne; Lucas, Nicolás; Reynier, Pascal; Descamps, Philippe; Guardiola, Philippe

doi:10.1093/humrep/der431

Cited by 42 publications

(36 citation statements)

References 109 publications

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“…Furthermore, there is no unique screening test for young patients [31,35]. Bidirectional paracrine oocyte-granulosa cell communication is necessary for normal follicular growth and oocyte development [22]. The maturation, development and quality of oocytes are provided through cumulus cells by growth factors, paracrine signals, secondary messenger and nutrient exchanges [3,5,17,22,37,41].…”

Section: Introductionmentioning

confidence: 99%

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis

2016

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Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses.

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Section: Introductionmentioning

confidence: 99%

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis

2016

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“…VCAN, an extracellular matrix component that mediates functional properties of the granulosa layer throughout folliculogenesis, which is required to ensure cumulus expansion and oocyte maturation, was increased in obese dams. Previous research demonstrated an increased expression of VCAN in patients with diminished ovarian reserve, which is associated with obesity, compared with normal patients (32). AURKB, which plays a critical role in chromosome-microtuble interaction and ensures chromosome segregation, was downregulated in obese dams.…”

Section: Discussionmentioning

confidence: 85%

Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1

Ruebel

Shankar

Gaddy

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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A. Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1. Am J Physiol Endocrinol Metab 311: E269 -E277, 2016. First published June 7, 2016 doi:10.1152/ajpendo.00524.2015.-Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n ϭ 7) compared with lean (LN; n ϭ 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P Ͻ 0.001), greater fat mass (P Ͻ 0.001), and reduced lean mass (P Ͻ 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P Ͻ 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (Ϯ1.3 fold, P Ͻ 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNF␣ in ovaries from OB compared with LN (P Ͻ 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P Ͻ 0.05), whereas nuclear levels of Egr-1 (P Ͻ 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P Ͻ 0.05) correlated with %visceral fat weight (r ϭ 0.51, Ϫ0.77, and Ϫ0.57, respectively, P Յ 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels.early growth response factor 1; gene expression; inflammation; obesity; reproduction IN THE US, 60% OF WOMEN OF REPRODUCTIVE AGE are either overweight or obese, which predisposes them to higher risk of infertility and pregnancy complications (12,21,57,59,60) and potentially leads to adverse effects on offspring development. Higher adiposity leads to hormonal dysregulation, decreased primordial follicle numbers at the initiation of follicular development, lower ovulation rates, a reduced number of cleaved blastocysts developing to eight cell stage and reduced implantation rates, and ultimately impaired reproductive function (11,16,17,22,33,35,61). Similarly, in experimental models, obesity leads to decreased primordial and preovulatory follicle numbers, increased follicular atresia and changes in steroidogenesis via decreased steroidogenic acute regulatory protein, and increased Cyp11a1 protein content in ovarian tissue (7,16,23,37,38,53,61). Evidence of lipid accumulation, endoplasmic reticulum stress, and oxidative stress in ova...

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“…PCOS compared to non-PCOS (Catteau-Jonard et al 2008, Wei et al 2012, Meng et al 2013, Schmidt et al 2014, Lan et al 2015, endometriosis compared to non-endometriosis , Allegra et al 2014, Barcelos et al 2015 and diminished ovarian reserve compared to normal ovarian reserve (Greenseid et al 2011, Jindal et al 2012, May-Panloup et al 2012) have all been shown to alter gene expression. In fact, PCOS patients with or without insulin resistance were shown to have DRGE compared to non-PCOS normal control patients (Kaur et al 2012).…”

Section: Variables Affecting Granulosa Cell Transcriptomic Profiles Omentioning

confidence: 99%

Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

Kordus

LaVoie

2017

Reproduction

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Cumulus and mural granulosa cells of the ovarian follicle surround and interact with the developing oocyte. These follicular cells reflect the oocyte's overall health and may indicate subsequent developmental competence of embryos. Biomarkers of granulosa cells associated with individual oocytes could potentially be used in assisted reproduction to indicate which embryos have the best chance of implanting in the uterus and completing gestation. In this review, we have performed a comprehensive assessment of the recent literature for human cumulus and mural granulosa cell mRNA biomarkers as they relate to pregnancy and live birth. A critical discussion of variables affecting granulosa gene expression profiles for in vitro fertilization patients, including patient demographics and ovarian stimulation regimens, is presented. Although studies with microarray data were evaluated, this synopsis focuses on expressed genes that have been validated by quantitative RT-PCR. Furthermore, we summarize the current published data that support or refute identified granulosa expressed genes as potential biomarkers of embryos that give rise to ongoing pregnancy and live birth. Finally, we review studies that offer predictive models for embryo selection for uterine transfer based on biomarkers that show differential gene expression. Reproduction (2017) 153 R69-R83

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Molecular characterization of corona radiata cells from patients with diminished ovarian reserve using microarray and microfluidic-based gene expression profiling

Abstract: Despite small sample size limitations, 12 genes deregulated in the CRC of DOR patients were identified, which could be involved in DOR pathogenesis. A DOR patient's subgroup with high baseline E(2) levels and deregulated estrogen-responsive genes was also identified.

Cited by 42 publications

References 109 publications

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis

Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis

Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1

Granulosa cell biomarkers to predict pregnancy in ART: pieces to solve the puzzle

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