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2015 ; 103
(3
): 845-52
Nephropedia Template TP
Fertil Steril
2015[Mar]; 103
(3
): 845-52
PMID25596622
show ga
OBJECTIVE: To determine whether transforming growth factor (TGF)-?3 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-? was blocked by two approaches: TGF-? pan-specific
antibody or transfection with a mutant TGF-? 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-? 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-?
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-?
antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF
repression. CONCLUSION(S): 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.
|Adult
[MESH]
|Bone Morphogenetic Protein 2/*pharmacology
[MESH]
free
free
free
