Reduction of progesterone receptor expression in human cumulus cells at the time of oocyte collection during IVF is associated with good embryo quality

Hasegawa, Junichi; Yanaihara, Atsushi; Iwasaki, Shinji; Otsuka, Yukiko; Negishi, Momoko; Akahane, Tomoko; Okai, Takashi

doi:10.1093/humrep/dei005

Cited by 49 publications

(44 citation statements)

References 29 publications

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“…The predictive role of gene expression in cumulus cells has been described before, with cyclooxygenase 2, GREM1, HAS2 (McKenzie et al 2004), PTX3 (Zhang et al 2005), and progesterone receptor (Hasegawa et al 2005) being identified as useful markers.…”

Section: Discussionmentioning

confidence: 81%

Association between human oocyte developmental competence and expression levels of some cumulus genes

Cillo¹,

Brevini²,

Abednatanzi³

et al. 2007

Reproduction

168

130

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At present, oocyte selection is mainly based upon morphological criteria but it is generally acknowledged that its reliability requires further improvement. The aim of this study was to determine whether transcript levels in cumulus cells can provide a useful marker of oocyte developmental competence in vitro. A retrospective study was performed on cumulus cells isolated from 90 oocytes retrieved from 45 patients. Upon fertilization, 35 oocytes originated good-quality embryos and 36 developed into poor-quality embryos, whereas 19 failed to be fertilized. Semi-quantitative measurement of hyaluronic acid synthase 2 (HAS2), gremlin1 (GREM1), and pentraxin 3 (PTX3) mRNAs was performed and data for all genes were obtained from all the samples. Cumulus cells isolated from oocytes that originated high-quality embryos on day 3 of culture had HAS2 and GREM1 transcript levels higher than those detected in cells from oocytes that did not fertilize or developed into poor-quality embryos. No differences were observed in PTX3 levels. Results indicate that the measurement of HAS2 and GREM1 levels in cumulus cells would reliably complement the morphological evaluation providing a useful tool for selecting oocytes with greater chances to be fertilized and develop in vitro.

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Section: Discussionmentioning

confidence: 81%

Association between human oocyte developmental competence and expression levels of some cumulus genes

Cillo¹,

Brevini²,

Abednatanzi³

et al. 2007

Reproduction

168

130

View full text Add to dashboard Cite

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“…In the present study, we investigated the changes in global gene expression in murine cumulus cells derived from IVM oocytes compared with IVV oocytes and elucidated the biological pathways most affected by in vitro culture systems. Cumulus cell gene expression is of great interest in identifying markers of human oocyte quality and has been the focus of many recent studies (McKenzie et al 2004;Hasegawa et al 2005;Zhang et al 2005;Cillo et al 2007;Feuerstein et al 2007;Hasegawa et al 2007;Gebhardt et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus–oocyte complexes

Kind

Banwell

Gebhardt

et al. 2013

Reprod. Fertil. Dev.

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The IVM of mammalian cumulus–oocyte complexes (COCs) yields reduced oocyte developmental competence compared with oocytes matured in vivo. Altered cumulus cell function during IVM is implicated as one cause for this difference. We have conducted a microarray analysis of cumulus cell mRNA following IVM or in vivo maturation (IVV). Mouse COCs were sourced from ovaries of 21-day-old CBAB6F1 mice 46 h after equine chorionic gonadotrophin (5 IU, i.p.) or from oviducts following treatment with 5 IU eCG (61 h) and 5 IU human chorionic gonadotrophin (13 h). IVM was performed in α-Minimal Essential Medium with 50 mIU FSH for 17 h. Three independent RNA samples were assessed using the Affymetrix Gene Chip Mouse Genome 430 2.0 array (Affymetrix, Santa Clara, CA, USA). In total, 1593 genes were differentially expressed, with 811 genes upregulated and 782 genes downregulated in IVM compared with IVV cumulus cells; selected genes were validated by real-time reverse transcription–polymerase chain reaction (RT-PCR). Surprisingly, haemoglobin α (Hba-a1) was highly expressed in IVV relative to IVM cumulus cells, which was verified by both RT-PCR and western blot analysis. Because haemoglobin regulates O2 and/or nitric oxide availability, we postulate that it may contribute to regulation of these gases during the ovulatory period in vivo. These data will provide a useful resource to determine differences in cumulus cell function that are possibly linked to oocyte competence.

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“…Progesterone plays a critical role in granulosa cell differentiation via the interaction with specific receptors (PGRs). The reduction of PGR gene expression is associated with better embryo quality in humans (29); therefore, the overexpression of PGR and the enzymes involved in the progesterone production in IVM-CC may decrease the developmental competence of IVM oocytes and embryos. The association of a higher level of PGR mRNA with COCs that will yield less competent embryos is consistent with the observation that higher-quality human embryos came from COCs with reduced levels of PGR (29).…”

Section: Discussionmentioning

confidence: 99%

“…The reduction of PGR gene expression is associated with better embryo quality in humans (29); therefore, the overexpression of PGR and the enzymes involved in the progesterone production in IVM-CC may decrease the developmental competence of IVM oocytes and embryos. The association of a higher level of PGR mRNA with COCs that will yield less competent embryos is consistent with the observation that higher-quality human embryos came from COCs with reduced levels of PGR (29). This classic nuclear PGR does not appear in mouse cumulus cells, although it is present in the granulosa cells of preovulatory follicles after the hCG stimulus (75), and similar transient expression in response to LH has also been demonstrated in the rat (54,55).…”

Section: Discussionmentioning

confidence: 99%

Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome

Lee¹,

VandeVoort

Gaughan

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Lee YS, VandeVoort CA, Gaughan JP, Midic U, Obradovic Z, Latham KE. Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome. Am J Physiol Endocrinol Metab 301: E196 -E209, 2011. First published April 12, 2011 doi:10.1152/ajpendo.00686.2010.-The elaboration of a quality oocyte is integrally linked to the correct developmental progression of cumulus cell phenotype. In humans and nonhuman primates, oocyte quality is diminished with in vitro maturation. To determine the changes in gene expression in rhesus monkey cumulus cells (CC) that occur during the final day prior to oocyte maturation and how these changes differ between in vitro (IVM) and in vivo maturation (VVM), we completed a detailed comparison of transcriptomes using the Affymetrix gene array. We observed a large number of genes differing in expression when comparing IVM-CC and VVM-CC directly but a much larger number of differences when comparing the transitions from the prematuration to the post-IVM and post-VVM states. We observed a truncation or delay in the normal pattern of gene regulation but also remarkable compensatory changes in gene expression during IVM. Among the genes affected by IVM are those that contribute to productive cell-cell interactions between cumulus cell and oocyte and between cumulus cells. Numerous genes involved in lipid metabolism are incorrectly regulated during IVM, and the synthesis of sex hormones appears not to be suppressed during IVM. We identified a panel of 24 marker genes, the expression of which should provide the foundation for understanding how IVM can be improved for monitoring IVM conditions and for diagnosing oocyte quality. oocyte quality; in vitro maturation LIFE BEGINS IN THE OOCYTE. The oocyte accumulates a remarkable and complex macromolecular reservoir that mediates and controls the initial development of each new individual while at the same time eliminating a range of molecules that promote gametogenesis but would otherwise impede early embryogenesis (8,36,37,67). Failure to complete these transitions appropriately yields an oocyte with limited developmental potential, unable to undergo fertilization or activation, or unable to sustain embryogenesis after fertilization and activation.Because of the key role of the oocyte in early development, understanding the molecular features that confer a high oocyte developmental potential is of paramount importance in reproductive biology. Such information will reveal the underlying mechanisms and processes that drive oogenesis and early embryogenesis. Moreover, such information will provide markers with which to screen and select high-quality oocytes for assisted reproduction in humans and could enhance success in agricultural reproductive biology and species conservation applications.The oocyte develops in close coordination with the somatic companion cells, particularly the cumulus oophorous cells, which maintain direct contact with the oocyte via transzonal processes and gap junctions until ovulation. Through its secretion...

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Reduction of progesterone receptor expression in human cumulus cells at the time of oocyte collection during IVF is associated with good embryo quality

Abstract: These results suggest that follicular LH or steroids do not affect PR expression, and full reduction of total PR expression on cumulus cells at the time of oocyte collection is associated with good morphology in human oocytes.

Cited by 49 publications

References 29 publications

Association between human oocyte developmental competence and expression levels of some cumulus genes

Association between human oocyte developmental competence and expression levels of some cumulus genes

Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus–oocyte complexes

Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome

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