Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx
ABSTRACT To determine whether women with hydrosalpinx would have diminished endometrial HOXA10 expression and whether salpingectomy would reverse HOXA10 suppression. The homeobox gene HOXA10 is a transcription factor that is necessary for embryo implantation; its expression in human endometrium correlates with receptivity and implantation. Increased endometrial HOXA10 expression may be one mechanism by which salpingectomy results in increased implantation rates in IVF.
Prospective clinical trial.
Academic medical center.
Women with unilateral or bilateral hydrosalpinx.
Expression of HOXA10 was examined prospectively during the midluteal phase in endometrium obtained from infertile women (n = 9) with hydrosalpinges before and after salpingectomy, as well as from fertile controls (n = 6). Quantitative HOXA10 mRNA expression was determined by real-time reverse-transcription polymerase chain reaction, and HOXA10 protein expression was determined by immunohistochemistry.
Expression of HOXA10 mRNA and protein.
Expression of HOXA10 mRNA was significantly lower in infertile women with hydrosalpinges, compared with the case of fertile controls. Salpingectomy resulted in a statistically significant, 15-fold increase in endometrial HOXA10 expression. Immunohistochemical analysis confirmed the quantitative real-time reverse-transcription polymerase chain reaction findings. Increased HOXA10 expression was evident in both glandular epithelial cells and endometrial stroma.
HOXA10 is necessary for implantation. Here, we demonstrate decreased HOXA10 expression in response to hydrosalpinx fluid as a potential molecular mechanism for diminished implantation rates. Salpingectomy restores endometrial HOXA10 expression. This may be one mechanism by which salpingectomy results in augmented implantation rates in IVF.
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ABSTRACT: We report the hysteroscopic findings in a 22 year old nulligravid patient with bilateral communicating hydrosalpinges. The inflamed hyperemic endometrial cavity encountered preoperatively normalized at second look hysteroscopy six months after bilateral tubal interruption. The patient underwent successful IVF with culmination in a singleton, live birth. We propose that an inflamed appearance at hysteroscopy, done for endometrial cavity screening, should prompt a dedicated study to rule out hydrosalpinx prior to proceeding with IVF treatment. To date, such a hysteroscopic endometrial phenotype in the presence of hydrosalpinx has not been well characterized.01/2012; 2012(1):8. DOI:10.1093/jscr/2012.1.8
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ABSTRACT: To determine whether transforming growth factor (TGF)-β3 is a paracrine signal secreted by leiomyoma that inhibits bone morphogenetic protein (BMP)-mediated endometrial receptivity and decidualization. Experimental. Laboratory. Women with symptomatic leiomyomas. Endometrial stromal cells (ESCs) and leiomyoma cells were isolated from surgical specimens. Leiomyoma-conditioned media (LCM) was applied to cultured ESC. The TGF-β was blocked by two approaches: TGF-β pan-specific antibody or transfection with a mutant TGF-β receptor type II. Cells were then treated with recombinant human BMP-2 to assess BMP responsiveness. Expression of BMP receptor types 1A, 1B, 2, as well as endometrial receptivity mediators HOXA10 and leukemia inhibitory factor (LIF). Enzyme-linked immunosorbent assay showed elevated TGF-β 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-β 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-β antibody or transfection with mutant TGF receptor prevented HOXA10 and LIF repression. Leiomyoma-derived TGF-β was necessary and sufficient to alter endometrial BMP-2 responsiveness. Blockade of TGF-β 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. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Fertility and Sterility 01/2015; 103(3). DOI:10.1016/j.fertnstert.2014.12.099 · 4.30 Impact Factor
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ABSTRACT: Background: Endometrial integrin expression changes might be a reason for implantation failure in polycystic ovarian syndromes (PCOS). Objective : Assessment of integrin genes and proteins expression upon endometrium in the PCOS experimental mouse model was the main goal of this study. Materials and Methods: 30 NMRI female mice were equally divided into control, experimental (PCOS; received estradiol valerate (40 mg/kg)) and sham group (received; olive oil). After 8 weeks, each group was hyper stimulated by 7 IU PMSG and then, after 48hrs, 7 IU HCG was injected. Vaginal plaque was checked. After 5 days, Progesterone and estradiol levels and endometrial tissues were investigated to evaluate of α4, αv, β1 and β3 integrins gene and protein by qPCR method and immunohistochemistry, respectively. Results: Tissue samples were assessed and showed that level of progesterone was significantly decreased in PCOS group. Results of molecular part in the amount of αv, β3, β1 and α4 gene expressions showed a great difference in β3 and αv genes expressions between experimental groups. αv, β3, α4 and β1 proteins in the endometrial stroma in the control group were expressed, but they were not detected in PCOS group. Conclusion: According to the results, integrins had different expression patterns in different areas of the endometrium; such as epithelial and stromal. It seems that in PCOS, this pattern has changed and the results might have a great influence on implantation failure. Therefore, this study suggests that a great attention to this problem may be essential in patients who are involved.Iranian Journal of Reproductive Medicine 10/2014; 12(10):687-694. · 0.19 Impact Factor