BMP-6 and SMAD4 gene expression is altered in cumulus cells from women with endometriosis-associated infertility

Acta Obstet Gynecol Scand. 2021 May;100(5):868-875. doi: 10.1111/aogs.13931. Epub 2020 Jul 6.

Abstract

Introduction: Oocyte competence and quality depend on communication between the oocyte and the cumulus and theca cells. In the preantral phase, the members of the transforming growth factor β (TGF-β) superfamily are responsible for this communication and play an important role in folliculogenesis. Members of the TGF-β superfamily are related to endometriosis (overexpression in the ectopic endometrium); however, few studies have explored these proteins as influencing fertility in endometriosis. Considering endometriosis-related infertility and to better understand the role of the TGF-β superfamily members in the antral phase in women with endometriosis, this research investigated the gene expression of the genes for ligands AMH, BMP-6, GDF-9, INHA, INHBB, and TGFβ3; receptors AMHR2, BMPR2, and TGFβR3; and intracellular signalling: SMAD3 and SMAD4.

Material and methods: The gene expression of AMH, BMP-6, GDF-9, INHA, INHBB, TGFβ3, AMHR2, BMPR2, TGFβR3, SMAD3, and SMAD4 in cumulus cells was investigated through quantitative real-time PCR in a case-control study including infertile women with and without peritoneal endometriosis undergoing in vitro fertilization.

Results: Age and outcomes of assisted reproduction were similar between the groups (P > .05). However, women with endometriosis showed reduced expression of BMP-6 and SMAD4 (P < .05) in cumulus cells compared with the control group, other genes did not present altered gene expression in women with endometriosis (P > .05).

Conclusions: The reduced expression of BMP-6 and SMAD4 in women with peritoneal endometriosis compared with the control group indicates that granulosa (cumulus) cell function could be altered in these women.

Keywords: BMP-6; SMAD4; cumulus cells; endometriosis; gene expression; infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Mullerian Hormone
  • Bone Morphogenetic Protein 6 / genetics*
  • Bone Morphogenetic Protein Receptors, Type II
  • Case-Control Studies
  • Cumulus Cells / metabolism*
  • Endometriosis / complications*
  • Female
  • Gene Expression*
  • Growth Differentiation Factor 9
  • Humans
  • Infertility, Female / complications*
  • Inhibin-beta Subunits
  • Inhibins
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Ligands
  • Proteoglycans
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • Smad3 Protein
  • Smad4 Protein / genetics*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta3

Substances

  • Bone Morphogenetic Protein 6
  • Growth Differentiation Factor 9
  • INHBB protein, human
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Proteoglycans
  • Receptors, Cell Surface
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • Smad3 Protein
  • Smad4 Protein
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta3
  • anti-Mullerian hormone receptor
  • inhibin A
  • betaglycan
  • Inhibins
  • Anti-Mullerian Hormone
  • Inhibin-beta Subunits
  • Bone Morphogenetic Protein Receptors, Type II