Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer

Gebhardt, Kathryn; Feil, D.; Dunning, Kylie R.; Lane, Michelle; Russell, Darryl L.

doi:10.1016/j.fertnstert.2011.04.033

Cited by 165 publications

(173 citation statements)

References 38 publications

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“…PTGS2) decreases cumulus expansion and slows the rate of embryo development in the in vitro bovine system (Nuttinck et al 2011). By contrast, higher PTGS2 mRNA levels occur in the cumulus cells of human oocytes expressing the highest developmental capacity (Gebhardt et al 2011). In cat COCs, we indeed observed increased PTGS2 mRNA expression after oocyte maturation in situ, which was consistent with earlier observations in the pig (Kawashima et al 2008) and mouse (Segi et al 2003).…”

Section: Discussionsupporting

confidence: 91%

“…This lack of differentiation in PTGS2 expression extended to COCs recovered during natural anestrus and supplemented in vitro with a low (1 mg/ml) FSH concentration, a treatment known to fail to circumvent inferior developmental capacity (Comizzoli et al 2003). Therefore, unlike reported for the cow (Assidi et al 2008) and human (McKenzie et al 2004, Gebhardt et al 2011, PTGS2 expression was not an accurate reflection of cat oocyte quality either in vivo or in vitro. EGR1, and specifically higher EGR1 expression in cumulus cells, has been described as an effective marker of oocyte developmental potential in cattle (Robert et al 2001, Tesfaye et al 2009).…”

Section: Discussionmentioning

confidence: 87%

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Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Hobbs

Howard²,

Wildt³

et al. 2012

Reproduction

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Domestic cat oocytes are seasonally sensitive to FSH. Compared with those collected during the breeding season, oocytes from the nonbreeding (NB) season require more FSH during in vitro maturation to achieve comparable developmental competence. This study tested the hypothesis that this seasonal variation was due to altered expression of FSH receptors (FSHR) and/or FSH-induced genes. Relative expression levels of FSHR mRNA and FSH-enhanced gene estrogen receptor b (ESR2) were measured by qPCR in whole ovaries and immature cumulus-oocyte complexes (COCs) isolated from cat ovaries during the natural breeding vs NB seasons. Expression levels of FSH-induced genes prostaglandin-endoperoxide synthase 2 (PTGS2), early growth response protein-1 (EGR1), and epidermal growth factor receptor (EGFR) were examined in mature COCs from both seasons that were a) recovered in vivo or b) matured in vitro with conventional (1 mg/ml) or high (10 mg/ml) FSH concentrations. Overall, FSHR mRNA levels were lower in whole ovaries during the NB compared with breeding season but were similar in immature COCs, whereas ESR2 levels did not differ in either group between intervals. We observed changes in PTGS2, EGR1, and EGFR mRNA expression patterns across maturation in COCs within but not between the two seasons. The lack of seasonal differentiation in FSH-related genes was not consistent with the decreased developmental capacity of oocytes fertilized during the NB season. These findings reveal that the seasonal decrease in cat oocyte sensitivity to FSH occurs both in vivo and in vitro. Furthermore, this decline is unrelated to changes in expression of FSHR mRNA or mRNA of FSH-induced genes in COCs from antral follicles.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 87%

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Hobbs

Howard²,

Wildt³

et al. 2012

Reproduction

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“…However, the success rate of IVF on the firstattempt,especiallyinolderfemales,islow.Predictivecriteria to select the best embryo for a single embryo transfer remain elusive. Tools for selecting embryos for transfer, such as visual morphological assessments, including blastocyst and blastocoels, and measurement of the hormone concentrations in follicular fluid, are often inadequate for identifying the embryo with the best potential to establish a pregnancy [4,14,15,20].…”

Section: Introductionmentioning

confidence: 99%

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient

Bayasula

Iwase

Kobayashi

et al. 2013

J Assist Reprod Genet

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Purpose Human follicular fluid constitutes the microenvironment of follicles and includes various biological active proteins that can affect follicle growth and oocyte fertilization. Conducting proteomic evaluations of human follicular fluid may be helpful for identifying potential biomarkers possibly possessing a predictive value for oocyte quality and the success of in vitro fertilization. Method We performed proteomic profiling of human follicular fluids containing oocytes that were fertilized and resulted in pregnancy and follicular fluids containing oocytes that were not fertilized in the same patients undergoing intracytoplasmic sperm injection using the LTQ Orbitrap coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analyses. ResultsWe identified a total of 503 proteins in human follicular fluids containing fertilized and non-fertilized oocytes obtained from 12 patients. We also found that 53 proteins exhibited significantly different spectral counts between the two groups, including heparan sulfate proteoglycan perlecan, which showed significant upregulation in the follicular fluids containing fertilized oocytes in comparison with that observed in the follicular fluids containing non-fertilized oocytes. Conclusion Our results suggest a possibility that proteins identified by LC/MS/MS in follicular fluid might not only be involved in folliculogenesis, but also function as biomarkers possessing predictive potential for oocyte maturation and the success of IVF when their expression levels are significantly different between fertilized and non-fertilized oocytes, although no distinctive biomarkers were identified in the current study.

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“…Prostaglandin-endoperoxide synthase 2 (PTGS2) and VCAN mRNA expression were shown to be significantly higher in CC from oocytes that led to a live birth, and GREM1 and phosphofructokinase, platelet (PFKP) mRNA expression was correlated with the baby's birth weight (Gebhardt et al 2011). These results came from a retrospective study evaluating pregnancy resulting from 38 SETs, and all patients had long downregulation protocols with rFSH.…”

Section: R78mentioning

confidence: 99%

“…In this retrospective study, they selected an 8 gene panel, HAS2, follicle=stimulating hormone receptor (FSHR), solute carrier family 2 member 4 (SLC2A4), activated leukocyte cell adhesion molecule (ALCAM), secreted frizzled-related protein 2 (SFRP2), VCAN, NRP1 and PGR based on prior published studies (McKenzie et al 2004, Gebhardt et al 2011, Wathlet et al 2011, Fragouli et al 2012, Iager et al 2013 to predict the mature oocytes that would lead to live birth. Based on their qRT-PCR results, it was determined that HAS2, FSHR, VCAN and PGR would be the best genes to rank the oocytes.…”

Section: Predictive Modelsmentioning

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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Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer

Cited by 165 publications

References 38 publications

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro

A proteomic analysis of human follicular fluid: comparison between fertilized oocytes and non-fertilized oocytes in the same patient

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

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