Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure

Koler, Moriah; Achache, Hanna; Tsafrir, Avi; Smith, Yoav; Revel, Ariel; Reich, Reuven

doi:10.1093/humrep/dep193

Cited by 125 publications

(101 citation statements)

References 32 publications

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“…Endometrial transcriptomic profiles have also been investigated under different controlled ovarian stimulation protocols (Simon et al 2005;Horcajadas et al 2008), or in the context of unexplained pathologies such as recurrent implantation failure (Tapia et al 2008;Koler et al 2009;Altmäe et al 2010), or other endometrial conditions (Table 1) (Habermann et al 2011;Matsuzaki 2011). Most of these studies investigate the transcriptomic signature in the whole endometrial tissue without separating the different compartments.…”

Section: Transcriptomics Of the Endometriummentioning

confidence: 99%

Human Endometrial Transcriptomics: Implications for Embryonic Implantation

Gómez

Ruiz-Alonso

Miravet

et al. 2015

Cold Spring Harb Perspect Med

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Human endometrium has been extensively investigated in the search for markers capable of predicting its receptive status. The completion of the Human Genome Project has triggered a rapid development of new fields in molecular biology, the "transcriptomics" being a major turning point in the knowledge acquisition of endometrial receptivity. Based on this, a customized Endometrial Receptivity Array (ERA) has been developed, which is capable of identifying the genomic signature of receptivity. This diagnostic tool showed that the window of implantation (WOI) is displaced in one out of four patients with implantation failure, allowing the identification of their personalized WOI. This strategy allows performing a personalized embryo transfer ( pET) on the day in which the endometrium is receptive. The combination of a systems biology approach and next-generation sequencing will overcome the limitations of microarrays, and will, in the future, allow elucidation of the mechanisms involved in embryo implantation.T he endometrium, which lines the inside of the uterine cavity, undergoes cyclic changes that are regulated by ovarian steroids. It can be subdivided into the basal layer that is responsible for its regenerative capacity, and the functional layer that undergoes proliferation, secretion, and tissue degeneration every month from menarche to menopause. Its aim is to prepare the optimal moment for embryonic implantation known as the window of implantation (WOI).The endometrial cycle comprises the menstrual, proliferative, and secretory phases. The proliferative phase, which corresponds to the ovarian follicular phase and increased production of estrogens, lasts until ovulation occurs. During this stage, the increasing estrogen levels cause the proliferation of the stromal cells as well as the elongation of the spiral arteries. After ovulation, with the appearance of progesterone secreted by the granulosa-luteal cells, the secretory phase begins. If implantation does not occur, the secretory phase ends, and the corpus luteum degenerates. Menstruation occurs owing to the drop of estrogen and progesterone, which resets the endometrium until pregnancy

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Section: Transcriptomics Of the Endometriummentioning

confidence: 99%

Human Endometrial Transcriptomics: Implications for Embryonic Implantation

Gómez

Ruiz-Alonso

Miravet

et al. 2015

Cold Spring Harb Perspect Med

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“…Several studies suggested that uterine receptivity is diminished during controlled ovarian hyperstimulation (COH) used in ART compared with natural cycles [13][14][15] . Although studies have shown alterations of molecules are related to endometrial receptivity in COH-treated subjects [16][17][18][19][20][21] , the impact of COH treatment on endometrial receptivity is still unclear.Homeobox (HOX) genes are the vertebrate homologs of the Drosophila homeotic selector genes, which contain a 60-amino acid homeodomain as a DNA-binding domain via a helix-turn-helix motif [22] . 31(4):535-542,2011 J Huazhong Univ Sci Technol［Med Sci］…”

mentioning

confidence: 99%

Association of controlled ovarian hyperstimulation treatment with down-regulation of key regulators involved in embryonic implantation in mice

Xiong

Zhang

Jin

et al. 2011

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The debate exists whether or not gonadotropin-releasing hormone (GnRH) analogs used in controlled ovarian hyperstimulation (COH) impair endometrial receptivity. Homeobox A11 (Hoxa11), Meis homeobox 1 (Meis1), cadherin 1 (Cdh1), and catenin beta 1 (Ctnnb1) are well known to be involved in successful implantation. In this study, the endometrial expression of Hoxa11, Meis1, Cdh1, and Ctnnb1 during the peri-implantation period was investigated in an in vitro fertilization (IVF) mouse model by real-time RT-PCR and Western blot to evaluate the relationship between Hoxa11, Meis1, Cdh1, and Ctnnb1 expression and the impact of the COH on endometrial receptivity. The mimic COH protocols included GnRH agonist plus human menopausal gonadotropin (HMG) (GnRH agonist group), GnRH antagonist plus HMG (GnRH antagonist group), and HMG alone (HMG group). The expression levels of Hoxa11, Meis1, Cdh1, and Ctnnb1 mRNA and protein were decreased in all of the COH groups. The expression levels of Hoxa11 and Ctnnb1 were the lowest in the GnRH agonist group, and those of Meis1 and Cdh1 were lower in the GnRH analog groups than the HMG group. There were positive correlations between the expression of Hoxa11 and Ctnnb1, as well as the expression of Meis1 and Cdh1 among all the groups. In conclusion, the COH protocols, particularly with GnRH analogs, suppressed Hoxa11, Meis1, Ctnnb1 and Cdh1 expression, in mouse endometrium during the peri-implantation period. Our data reveal a novel molecular mechanism by which the COH protocols might impair endometrial receptivity.

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“…Using a specific primer for human Tert, real-time PCR was performed for investigating the mRNA level of Tert. Additionally, changes in ER alpha and PR expression were also analyzed as they are indispensible in embryo implantation (Carranza-Lira et al, 2000;Koler et al, 2009;Cha et al, 2012). Compared to the control, the RIF group showed a substantial increase in Tert expression and a significant reduction in ER alpha expression, whereas no evident change was observed in PR expression ( Figure 1A).…”

Section: Changes In Tert Er Alpha and Pr Mrna Expression During Implmentioning

confidence: 99%

“…In humans, the putative implantation window occurs at the mid secretory phase, and is precisely controlled by synergistic signals of progesterone and estrogen, which bind to the progesterone receptor (PR) and estrogen receptor (ER), respectively (Carson et al, 2000;Groothuis et al, 2007;Large and DeMayo, 2012). In the endometrium with recurrent implantation failure (RIF), approximately 8% of the downregulated genes are associated with compromised estrogen signals, due to decreased expression of ER alpha (Carranza-Lira et al, 2000;Koler et al, 2009). However, the molecular mechanisms responsible for recurrent implantation failure remain largely unclear.…”

Section: Introductionmentioning

confidence: 99%

Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure

Long

Liu

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Telomerase plays a critical role in cell proliferation and senescence, but the exact involvement of endometrial telomerase in recurrent implantation failure (RIF) is unknown. We collected endometrial biopsies from RIF patients (N = 30) and fertile women (N = 30). Real-time PCR was performed for detecting changes in telomerase reverse transcriptase (Tert), ER alpha, and PR expression at the transcript level, and the correlation between the variable expressions of these genes was tested using regression analysis. Then, western blot and immunohistochemistry were used to analyze the expression profiles of TERT and ER alpha at the protein level. Compared to the control, Tert expression was substantially increased, whereas ER alpha expression significantly decreased in the endometrium with RIF. No change was observed in PR expression. Tert expression was inversely associated with ER alpha expression. TERT protein expression in RIF patients was also clearly elevated, and was localized to both the endometrial epithelium and stromal cells. However, the signals for ER alpha in the stromal cells were weaker than those in the control. Expression of endometrial telomerase was substantially enhanced as ER alpha decreased in RIF patients during the implantation window.

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Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure

Abstract: The evaluation of the endometrium of RIF patients by gene array analysis demonstrates that the expression of various genes is altered, including those belonging to the cell cycle, Wnt signaling and cellular adhesion pathways.

Cited by 125 publications

References 32 publications

Human Endometrial Transcriptomics: Implications for Embryonic Implantation

Human Endometrial Transcriptomics: Implications for Embryonic Implantation

Association of controlled ovarian hyperstimulation treatment with down-regulation of key regulators involved in embryonic implantation in mice

Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure

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