Leiomyoma-derived transforming growth factor-ß impairs bone morphogenetic protein-2-mediated endometrial receptivity  

Oleh:

Doherty, Leo F. ; Taylor, Hugh S.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 103 no. 03 (Mar. 2015), page 845-852.
Topik: Leiomyoma; endometrial receptivity; bone morphogenetic protein; transforming growth factor-ß

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K Non-tandon: tidak ada Tandon: 1

Lihat Detail Induk

Isi artikel

Objective To determine whether transforming growth factor (TGF)-ß3 is a paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein (BMP)-mediated endometrial receptivity and decidualization. Design Experimental. Setting Laboratory. Patient(s) Women with symptomatic leiomyomas. Intervention(s) Endometrial stromal cells (ESCs) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. The TGF-ß was blocked by two approaches: TGF-ß pan-specific antibody or transfection with a mutant TGF-ß receptor type II. Cells were then treated with recombinant human BMP-2 to assess BMP responsiveness. Main Outcome Measure(s) Expression of BMP receptor types 1A, 1B, 2, as well as endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF). Result(s) Enzyme-linked immunosorbent assay showed elevated TGF-ß levels in LCM. LCM treatment of ESC reduced expression of BMP receptor types 1B and 2 to approximately 60% of pretreatment levels. Preincubation of LCM with TGF-ß neutralizing antibody or mutant TGF receptor, but not respective controls, prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in recombinant human BMP-2 treated, LCM exposed ESC. Pretreatment of LCM with TGF-ß antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Conclusion(s) Leiomyoma-derived TGF-ß was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-ß prevents repression of BMP-2 receptors and restores BMP-2-stimulated expression of HOXA10 and LIF. Blockade of TGF signaling is a potential strategy to improve infertility and pregnancy loss associated with uterine leiomyoma.

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