Granulosa cells of polycystic ovaries: are they normal or abnormal?

Erickson, Gregory F.; Magoffin, Denis A.; Garzo, V. Gabriel; Cheung, Anthony P.; Chang, R. Jeffrey

doi:10.1093/oxfordjournals.humrep.a137638

Cited by 154 publications

(73 citation statements)

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“…It activates FSH receptors (FSHRs) in granulosa cells of antral follicles leading to the transcription of aromatase (CYP19), a key enzyme that catalyzes the conversion of androgens to estrogens (Payne & Hales 2004, Stocco 2008, which is required for follicle maturation (Chen et al 2012). In PCOS, the expression of FSHR in granulosa cells appears to be up-regulated (Catteau-Jonard et al 2008), which is believed to be responsible for the observed hyperresponsiveness of PCOS granulosa cells to FSH both in vitro and in vivo (Erickson et al 1992, Mason et al 1994, Coffler et al 2003. Although FSH hypersensitivity accelerates estrogen production, PCOS women were found unable to sustain their estrogen level (Coffler et al 2003).…”

Section: Introductionmentioning

confidence: 99%

“…We have observed in the IVF clinic that PCOS patients undergoing ART treatment have various ovarian responses to exogenous FSH, from insufficient to overstimulated, probably because of the complicated FSH-regulatory system in PCOS (Erickson et al 1992, Mason et al 1994, Coffler et al 2003. The following procedures for ART often had to be cancelled either due to the lack of oocyte numbers or to avoid possible development of ovarian hyperstimulation syndrome, a life-threatening complication.…”

Section: Introductionmentioning

confidence: 99%

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Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Yang¹,

Ruan²,

Yang³

et al. 2015

Reproduction

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Women with polycystic ovary syndrome (PCOS) undergoing IVF-embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.Reproduction (2015) 150 289-296

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Yang¹,

Ruan²,

Yang³

et al. 2015

Reproduction

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show abstract

“…For PCOS patients, the apoptosis level is increased in granulosa cells [26]. Moreover, PCOS granulosa cells, unlike normal granulosa cells, show a limited capacity to synthesize progesterone, either spontaneously or in response to follicle-stimulating hormone (FSH) stimulation [27]. However, the dysfunction of cumulus cells in PCOS and how lncRNAs regulate the pathogenesis of PCOS in cumulus cells remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

Huang

Hao

Bao

et al. 2015

J Assist Reprod Genet

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Purpose To describe the long noncoding RNA (lncRNA) profiles in cumulus cells isolated from polycystic ovary syndrome (PCOS) patients by employing a microarray and in-depth bioinformatics analysis. This information will help us understand the occurrence and development of PCOS. Methods In this study, we used a microarray to describe lncRNA profiles in cumulus cells isolated from ten patients (five PCOS and five normal women). Several differentially expressed lncRNAs were chosen to validate the microarray results by quantitative RT-PCR (qRT-PCR). Then, the differentially expressed lncRNAs were classified into three subgroups (HOX loci lncRNA, enhancer-like lncRNA, and lincRNA) to deduce their potential features. Furthermore, a lncRNA/mRNA co-expression network was constructed by using the Cytoscape software (V2.8.3, http://www.cytoscape.org/). Results We observed that 623 lncRNAs and 260 messenger RNAs (mRNAs) were significantly up-or down-regulated (≥2-fold change), and these differences could be used to discriminate cumulus cells of PCOS from those of normal pat i e n t s . F i v e d i f f e r e n t i a l l y e x p r e s s e d l n c R N A s (XLOC_011402, ENST00000454271, ENST00000433673, ENST00000450294, and ENST00000432431) were selected to validate the microarray results using quantitative RT-PCR (qRT-PCR). The qRT-PCR results were consistent with the microarray data. Further analysis indicated that many differentially expressed lncRNAs were transcribed from chromosome 2 and may act as enhancers to regulate their neighboring protein-coding genes. Forty-three lncRNAs and 29 mRNAs were used to construct the coding-non-coding gene coexpression network. Most pairs positively correlated, and one mRNA correlated with one or more lncRNAs. Conclusions Our study is the first to determine genome-wide lncRNA expression patterns in cumulus cells isolated from PCOS patients by microarray. The results show that clusters of lncRNAs were aberrantly expressed in cumulus cells of PCOS patients compared with those of normal women, which revealed that lncRNAs differentially expressed in PCOS and normal women may contribute to the occurrence of PCOS and affect oocyte development.

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“…In PCOS, physiological levels of FSH [60,61] and IGF-I [54] have been demonstrated in follicular fluids, and the defect in PCOS is not due to a lack of stimulating hormone per se or a decreased responsiveness of the granulosa aromatase to IGFs and/or FSH [60- 1). This hypothesis is supported by experimental observations that IGFBPs attenuate FSHinduced steroid production in ovarian granulosa cells [71].…”

Section: Somatotropic Axis In Pcosmentioning

confidence: 99%

Clinical Implications of Insulin-Like Growth Factors and Their Binding Proteins in Reproduction.

Yoshimura

2000

Endocr J

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Granulosa cells of polycystic ovaries: are they normal or abnormal?

Cited by 154 publications

References 0 publications

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Aberrant expression of long noncoding RNAs in cumulus cells isolated from PCOS patients

Clinical Implications of Insulin-Like Growth Factors and Their Binding Proteins in Reproduction.

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