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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

  • ASSISTED REPRODUCTION TECHNOLOGIES
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Abstract

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 MII-oocytes 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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Acknowledgments

We wish to thank the Laboratory of Gynecology and Obstetrics, the Laboratory of Neuroendocrinology in the Department of Internal Medicine, and the Laboratory of Molecular Biology in the Department of Pediatrics at the Clinical Hospital of the Medical College of Ribeirão Preto – São Paulo University, for laboratory procedures. We would also like to thank Claudia Paz for statistical analysis support and Maria Cristina Picinato and Rosane Gomes de Paula Queiroz for technical assistance.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics - Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Luciana Ochuiuto Teixeira de Resende, Alessandra Aparecida Vireque, Laura Ferreira Santana, Ana Carolina Japur de Sá Rosa e Silva, Rui Alberto Ferriani & Rosana Maria Reis

  2. Department of Pediatrics - Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    Daniel Antunes Moreno & Carlos Alberto Scrideli

  3. Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto/USP, Av. Bandeirantes 3900, Campus Universitário, CEP 14049-900, Ribeirão Preto, SP, Brazil

    Rosana Maria Reis

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  1. Luciana Ochuiuto Teixeira de Resende
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  2. Alessandra Aparecida Vireque
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Correspondence to Rosana Maria Reis.

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Supported by CNPq – 478912/2007.

Capsule

Women with PCOS undergoing COH have increased expression of BMP15 and GDF9 genes in mature oocytes. BMPR2 expression in PCOS cumulus cells might be regulated by androgens.

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de Resende, L.O.T., Vireque, A.A., Santana, L.F. et al. 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. J Assist Reprod Genet 29, 1057–1065 (2012). https://doi.org/10.1007/s10815-012-9825-8

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  • DOI: https://doi.org/10.1007/s10815-012-9825-8

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