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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Fertil+Steril 2015 ; 103 (3): 845-52 Nephropedia Template TP
Fertil Steril 2015[Mar]; 103 (3): 845-52 PMID25596622show ga
Objective: To determine if TGF-?3 is a paracrine signal secreted by leiomyoma that inhibits BMP mediated endometrial receptivity and decidualization. Design: Experimental Setting: Laboratory Patients: Women with symptomatic leiomyomas Interventions: Endometrial stromal cells (ESC) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. TGF-? was blocked by two approaches: TGF-? pan-specific antibody or transfection with a mutant TGF-? receptor type II. Cells were then treated with rhBMP-2 to assess BMP responsiveness. Main Outcome Measures: Expression of BMP receptor types 1A (BMPR1A), 1B (BMPR1B), 2 (BMPR2), as well as endometrial receptivity mediators HOXA10 and LIF. Results: ELISA showed elevated TGF-? levels in LCM. LCM treatment of ESC reduced expression of BMPR1B and BMPR2 to approximately 60% of pretreatment levels. Pre-incubation of LCM with TGF-? neutralizing antibody or mutant TGF receptor, but not respective controls, prevented repression of BMP receptors. HOXA10 and LIF expression was repressed in rhBMP-2 treated, LCM exposed ESC. Pre-treatment of LCM with TGF-? antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Conclusions: Leiomyoma derived TGF-? was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-? 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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Fertil+Steril 2015 ; 103 (3): 845-52
