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

Abstract

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. 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. 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). 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.