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Leiomyomata and Reproduction
Published in John C. Petrozza, Uterine Fibroids, 2020
Leiomyomata are responsive to sex steroids and secrete and respond to inflammatory and vasoactive factors. Aberrant excessive production of transforming growth factor-beta (TGF-β), a multifunctional cytokine, from fibroids has been reported by several investigators [10,11] and has been implicated in altered implantation of the embryo [12]. Homeobox A10 (HOXA-10) is one of the most recognized gene sequences in mammalian implantation. Lower levels of expression have been identified in endometrial specimens in patients with fibroids [13,14]. Altered growth-factor secretion may lead to abnormal vasculature, characterized by dilated venous plexuses and disordered angiogenesis [15,16].
Uterine fibroids and the endometrium
Published in Carlos Simón, Linda C. Giudice, The Endometrial Factor, 2017
Deborah E. Ikhena, Serdar E. Bulun
Homeobox genes are transcription factors, and homeobox A10 (HOXA10) and homeobox A11 (HOXA11) are expressed in the female reproductive system (47). HOXA10 is essential for implantation, as knockout mice are infertile due to implantation failure. However, embryos from HOXA10 knockout mice are able to grow normally in wild-type mice, demonstrating that the defect lies with endometrial receptivity to implantation and not with the embryos themselves (55). HOXA10 expression is decreased in the endometrium of women with submucosal fibroids; this reduction is most prominent in the endometrium overlying the fibroid, but is also observed in the entire endometrium (23). Women with intramural fibroids also have significantly lower HOXA10 expression in ESFs than in healthy fertile controls. In fact, 68.8% of women with fibroids have decreased HOXA10 protein expression (56). BMP2 also mediates HOXA10 expression; thus, increased endometrial resistance to BMP2 may be a mechanism underlying decreased HOXA10 expression in the endometrium of these patients (22).
Mucosal biomarkers for endometrial receptivity: A promising yet underexplored aspect of reproductive medicine
Published in Systems Biology in Reproductive Medicine, 2022
Mark Jain, Larisa Samokhodskaya, Elena Mladova, Olga Panina
Endometrial epithelial cells at the time of ET might serve as the best sources of information regarding ER in the current IVF cycle. However, it is difficult to imagine an ethics committee that allows traumatizing endometrial biopsy immediately after (or prior to) ET. A sophisticated approach to solve this issue was proposed by Camargo-Díaz et al. (2017) (n = 76), who used the ET cannula leftover cells and mucus as a biomaterial for ER assessment. Hematoxylin-eosin staining with microscopic evaluation confirmed that cells that were attached to the ET cannula were mostly of endometrial origin. Total RNA was isolated from a mixture of endometrial epithelial cells and mucus. The levels of mucin 1 (MUC-1), homeobox A10 (HOXA-10), LIF, and colony stimulating factor-1 (CSF-1) RNA molecules were selected as ER biomarkers because of their altered expression profiles in infertile patients (Othman et al. 2012). LIF and CSF-1 were significantly upregulated in pregnant patients (p < 0.05). The increased LIF expression contradicts the previously discussed results of Lédée-Bataille et al. (2002), who observed a significant decrease in LIF levels in the endometrial fluid of pregnant patients and confirmed the results of Laird et al. (1997), who compared fertile and infertile women. Thus, the ability of LIF to reflect the ER remains unclear and requires further investigation.
Nur77 promotes embryo adhesion by transcriptionally regulating HOXA10 expression
Published in Systems Biology in Reproductive Medicine, 2020
Jingtao Shen, Xudong Zhu, Mei Zhang, Yue Jiang, Guijun Yan, Zhilong Wang, Lihua Sun, Qun Zhang
Several key factors, such as leukemia inhibitory factor (LIF) (Aghajanova 2010.), integrin β3 (ITGB3) (Achache and Revel 2006) and homeobox A10 (HOXA10) (Daftary et al. 2002), have been reported to participate in the regulation of the attachment process. HOXA10, which is a key transcriptional factor being considered to be a biomarker of endometrial receptivity, binds to the DNA sequence TAAT or TTAT on downstream target genes to regulate their transcriptional expression (Eun Kwon and Taylor 2004). For example, HOXA10 binds to a 41-bp TTAT-containing sequence on the ITGB3 promoter region to activate ITGB3 expression and promote embryo adhesion (Daftary et al. 2002). HOXA10 is dynamically expressed in the endometrial glands and stroma under the regulation of estrogen and progesterone throughout the menstrual cycle, reaching a peak in the middle and late stages of secretion (Taylor et al. 1998). In addition, HOXA10 is also regulated by several other factors, such as HB-EGF (Liu et al. 2007), VitD (Du et al. 2005), and IL-1β (Sarno et al. 2009). The expression level of HOXA10 is decreased in the endometrium of women with endometriosis (Zanatta et al. 2010), hydrosalpinx (Daftary and Taylor 2002), and polycystic ovary syndrome (Cermik et al. 2003), which may cause infertility. Furthermore, reduced expression of HOXA10 in the endometrial glandular epithelium has been clearly observed in recurrent implantation failure (RIF) patients (Yang et al. 2017). However, the mechanism of downregulated HOXA10 expression in implantation failure remains unclear.
Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?
Published in Expert Review of Proteomics, 2018
Mustapha Benkhalifa, Yosra Zayani, Véronique Bach, Henri Copin, Moncef Feki, Moncef Benkhalifa, Monia Allal-Elasmi
The pinopodes’ role is not fully understood; they absorb uterine fluid at the implantation site, which seems to be essential for attachment of the embryo to the endometrial epithelium. In fact, many proteins are involved in the formation of pinopodes, including leukemia inhibitory factor (LIF), homeobox A10, integrin αvβ3, heparin-binding EGF-like growth factor, and mucin-1 (MUC-1). The latter is a membrane glycoprotein that has been intensively studied in the endometrial epithelium and it was proposed as an anti-adhesion molecule which may prevent the pinopodes from exerting their function in embryo attachment [77,78]. In vitro studies of cocultured epithelial cells and human embryos revealed that when the blastocyst adheres to epithelial cells, there is paracrine inhibition of MUC-1 at the implantation site [79].