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Fibroblast growth factor 2 regulates cumulus differentiation under the control of the oocyte

Journal of Assisted Reproduction and Genetics volume 36, pages 905–913 (2019)Cite this article

Abstract

Purpose

We first assessed regulation of FGF2 expression in cumulus cells by FSH and oocyte-secreted factors during in vitro maturation (IVM). Then, we tested the hypothesis that FGF2 regulates meiotic progression, cumulus expansion, and apoptosis in cumulus-oocyte complexes (COC) undergoing IVM.

Methods

In vitro maturation of bovine COC was utilized as a model to assess regulation of FGF2 expression by FSH and oocyte-secreted factors (via microsurgical removal of the oocyte), as well as effects of graded doses of FGF2 on meiotic progression, degree of cumulus expansion, dissociation of cumulus cells, and cumulus cells apoptosis. Expression of genes regulating functional endpoints altered by FGF2 treatment was assessed in cumulus cells by real-time PCR. Cultures were replicated 4–5 times and effects of treatments were tested by ANOVA.

Results

FGF2 mRNA expression was increased by FSH and oocyte-secreted factors during IVM. Addition of FGF2 to the IVM medium advanced meiosis resumption, decreased the ease with which cumulus cells were dissociated, and inhibited cumulus cells apoptosis. Decreased cumulus dissociation was accompanied by decreased expression of TNFAIP6.

Conclusions

This is the first study showing that FGF2 expression is regulated by the oocyte in cumulus cells. Moreover, we report novel effects of FGF2 on cumulus cell survival and extracellular matrix (ECM) quality during IVM that may favor acquisition of developmental competence and suggest physiological roles during the final steps of COC differentiation.

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Acknowledgments

The authors thank FAPESP and CNPq for financial support. We thank Dr. Alberto M. Luciano for critical reading and suggestions.

Funding

This work was supported by Sao Paulo research foundation (FAPESP—Grant 12/06417-8) and National Council for Scientific and Technological Development (CNPq—Grant 312521/2014-6).

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Affiliations

  1. Departamento de Fisiologia, Instituto de Biociências, Universidade Estadual Paulista, Rubião Junior, Botucatu, São Paulo, 18618-970, Brazil

    Rodrigo G. Barros, Paula F. Lima, Ana Caroline S. Soares, Lorena Sanches & José Buratini

  2. Centre de Recherche en Reproduction et Fertilité, Faculté de Médecine Vétérinaire, Université de Montréal, St-Hyacinthe, Québec, J2S 7C6, Canada

    Christopher A. Price

Authors
  1. Rodrigo G. Barros
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  2. Paula F. Lima
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  3. Ana Caroline S. Soares
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  4. Lorena Sanches
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  5. Christopher A. Price
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  6. José Buratini
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Correspondence to Rodrigo G. Barros.

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Barros, R.G., Lima, P.F., Soares, A.C.S. et al. Fibroblast growth factor 2 regulates cumulus differentiation under the control of the oocyte. J Assist Reprod Genet 36, 905–913 (2019). https://doi.org/10.1007/s10815-019-01436-7

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  • DOI: https://doi.org/10.1007/s10815-019-01436-7

Keywords

  • FGF2
  • IVM
  • Oocyte-secreted factors
  • Meiosis
  • Cumulus expansion
  • Apoptosis