Abnormal expression of growth differentiation factor 9 and bone morphogenetic protein 15 in stimulated oocytes during maturation from women with polycystic ovary syndrome

Wei, Li‐Na; Liang, Xiaoyan; Fang, Cong; Zhang, Minfang

doi:10.1016/j.fertnstert.2011.05.036

Cited by 56 publications

(39 citation statements)

References 24 publications

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“…Highlighting the gene expression profiles of PCOS oocytes, previous microarray analyses have demonstrated that more than 80 % of differentially expressed genes in PCOS oocytes had increased mRNA abundance compared with oocytes from normal women, and indicated that androgens may play a role in this process [5]. Our results are in striking contrast with a recent study employing Nested-PCR analysis of oocyte pools (n07), in which a lower expression of GDF9 and BMP15 genes was observed in stimulated mature PCOS oocytes [20]. The reasons for these discrepancies are unknown, but could be attributed to stagedependent differences or oocyte quality, follicular diameter, or sensitivity and specificity of the PCR analysis (Nested-PCR vs. Real-Time PCR in the present study).…”

Section: Discussioncontrasting

confidence: 99%

“…To our knowledge, there are only two case-control studies that focus on GDF9 and BMP15 expression in oocytes and/or CCs of infertile PCOS women undergoing in vitro fertilization and embryo transfer (IVF-ET) [20,21]. The established role of GDF9 and BMP15 in oocyte competence, and recent findings that single-nucleotide polymorphism variants in these genes seem connected with hyperstimulation syndrome and anovulation and infertility in women with PCOS, led us to evaluate the expression of these genes in single mature oocytes and the expression of BMPR2 in their respective cumulus cells from women with PCOS.…”

Section: Introductionmentioning

confidence: 99%

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Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

Resende

Vireque

Santana

et al. 2012

J Assist Reprod Genet

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Purpose To detect expression of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) in oocytes, and their receptor type 2 receptor for BMPs (BMPR2) in cumulus cells in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF), and determine if BMPR2, BMP15, and GDF9 expression correlate with hyperandrogenism in FF of PCOS patients. Methods Prospective case-control study. Eighteen MIIoocytes and their respective cumulus cells were obtained from 18 patients with PCOS, and 48 MII-oocytes and cumulus cells (CCs) from 35 controls, both subjected to controlled ovarian hyperstimulation (COH), and follicular fluid (FF) was collected from small (10-14 mm) and large (>18 mm) follicles. RNeasy Micro Kit (Qiagen ® ) was used for RNA extraction and gene expression was quantified in each oocyte individually and in microdissected cumulus cells from cumulus-oocyte complexes retrieved from preovulatory follicles using qRT-PCR. Chemiluminescence and RIA assays were used for hormone assays. Results BMP15 and GDF9 expression per oocyte was higher among women with PCOS than the control group. A positive correlation was found between BMPR2 transcripts and hyperandrogenism in FF of PCOS patients. Progesterone values in FF were lower in the PCOS group. Conclusion We inferred that BMP15 and GDF9 transcript levels increase in mature PCOS oocytes after COH, and might inhibit the progesterone secretion by follicular cells in PCOS follicles, preventing premature luteinization in cumulus cells. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

Resende

Vireque

Santana

et al. 2012

J Assist Reprod Genet

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show abstract

“…These findings may thus suggest a role for this pathway in the ovarian abnormalities typical of PCOS. Consistently, some recent studies have reported that GDF9 mRNA expression in oocyte and cumulus granulosa cells is abnormally reduced in PCOS women (44,45).…”

Section: European Journal Of Endocrinologysupporting

confidence: 83%

Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome

Tosi

Sarra

Bonin

et al. 2014

European Journal of Endocrinology

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Objective: Pentraxin-3 (PTX3), like C-reactive protein (CRP), is an acute-phase protein that belongs to the pentraxin superfamily. Moreover, it is expressed in the cumulus oophorus and appears to be involved in female fertility. The aim of the present study was to assess whether PTX3 levels are altered in polycystic ovary syndrome (PCOS) women and whether they show any relationship with the main features of these subjects. Design: A cross-sectional study was conducted at the outpatient clinic of an academic centre. Methods: A total of 66 women affected with PCOS and 51 healthy controls were studied. Plasma PTX3 and serum CRP were measured by ELISA. Androgens were measured by liquid chromatography-mass spectrometry and free testosterone was measured by equilibrium dialysis. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique. Results: Adjusting for age and BMI, plasma PTX3 was reduced in PCOS women (PZ0.036), in contrast with serum CRP, which was increased (PZ0.004). In multiple regression analysis, serum androgens and other endocrine and ovarian features of PCOS were predictors of PTX3 levels, whereas body fat was the main independent predictor of CRP concentrations. Conclusions: Plasma PTX3 levels were reduced in PCOS women and independently associated with hyperandrogenism and other endocrine and ovarian features of PCOS.

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“…It was shown that GDF9 was essential for follicular development in mice, once growth initiation had occurred. 34 Subsequently, this was also shown to be true in sheep, 11,35 and in women where abnormal GDF9 concentrations have been linked to premature ovarian failure, 36 polycystic ovarian syndrome (PCOS), [37][38][39] diminished ovarian reserve, 40 and dizygotic twinning. 41 Interestingly, in sheep, but not mice, inactivating mutations in another oocyte-derived growth factor, bone morphogenetic protein 15 (BMP15) were also found to inhibit ovarian follicular development after growth initiation.…”

Section: Oocyte-specific Growth Factors and Gonadotropinsmentioning

confidence: 99%

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

McNatty¹,

Juengel²,

Pitman³

2014

Reproductive Biology Insights

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ABSTRACT:The use of exogenous gonadotropins to increase oocyte yields for better pregnancy outcomes remains unpredictable and inefficient. The objectives of this review are to address two questions concerning this issue: (1) are there any alternatives for improving consistency in oocyte yields? (2) is it possible to develop a molecular diagnostic test for oocytes with blastocyst potential? Studies in sheep with a heterozygous inactivating mutation in the oocyte-derived growth factor, bone morphogenetic protein 15 (BMP15), report increased oocyte yields and significantly more offspring. Moreover, partial immuno-neutralization of BMP15 bioactivity increases oocyte yield without modifying gonadotropin or ovarian steroid secretion. Therefore, it is hypothesized that the development of BMP15 antagonists may prove them to be suitable alternatives to exogenous gonadotropins. Recent evidence from analyses of candidate gene expression in human cumulus cells separated from individual oocytes before IVF indicates a potential non-invasive molecular screen for oocytes with improved blastocyst and live-birth outcomes.

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Abnormal expression of growth differentiation factor 9 and bone morphogenetic protein 15 in stimulated oocytes during maturation from women with polycystic ovary syndrome

Cited by 56 publications

References 24 publications

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

Plasma levels of pentraxin-3, an inflammatory protein involved in fertility, are reduced in women with polycystic ovary syndrome

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

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