0000000000017134
AUTHOR
Patricia Sebastian-leon
Window of implantation transcriptomic stratification reveals different endometrial subsignatures associated with live birth and biochemical pregnancy
Objective To refine the endometrial window of implantation (WOI) transcriptomic signature by defining new subsignatures associated to live birth and biochemical pregnancy. Design Retrospective cohort study. Setting University-affiliated in vitro fertilization clinic and reproductive genetics laboratory. Patient(s) Healthy fertile oocyte donors (n = 79) and patients with infertility diagnosed by Endometrial Receptivity Analysis (n = 771). Intervention(s) None. Main Outcome Measure(s) WOI transcriptomic signatures associated with specific reproductive outcomes. Result(s) The retrospective cohort study was designed to perform a prediction model based on transcriptomic clusters for endometrial …
Machine Learning-Based Approach Highlights the Use of a Genomic Variant Profile for Precision Medicine in Ovarian Failure
Ovarian failure (OF) is a common cause of infertility usually diagnosed as idiopathic, with genetic causes accounting for 10–25% of cases. Whole-exome sequencing (WES) may enable identifying contributing genes and variant profiles to stratify the population into subtypes of OF. This study sought to identify a blood-based gene variant profile using accumulation of rare variants to promote precision medicine in fertility preservation programs. A case–control (n = 118, n = 32, respectively) WES study was performed in which only non-synonymous rare variants <
P–294 Mapping COVID–19 affected genes from blood in a Window of implantation co-expression network reveals a potentially compromised landscape
Abstract Study question Could the transcriptomic and functional landscape of the window of implantation be compromised by SARS-COV–2 infection? Summary answer Some of the main genes and pathways involved in the window of implantation are affected in blood of COVID–19 patients and receptivity could be affected. What is known already There is a concern whether SARS-COV–2 can disrupt assisted reproduction treatments (ARTs) and fertility in short and long terms. In the endometrium, it was found that genes related to the viral infection (ACE2, TMPRSS2/4, CTSL/B) are involved in menstrual cycle progression, especially in the Window of Implantation (WOI). However, there are no studies describing t…
Understanding disease mechanisms with models of signaling pathway activities
Background Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is one of the main challenges in the analysis of genomic data and is on the basis of the future implementation of precision medicine. Results Here we propose a simple probabilistic model in which signaling pathways are separated into elementary sub-pathways or signal transmission circuits (which ultimately trigger cell functions) and then transforms gene expression measurements into probabilities of activation of such signal transmission circuits. Using this model, differential activation of such circuits between biological conditions can be estimated. Thus, circuit activation s…
SARS-CoV-2 infection risk assessment in the endometrium: viral infection-related gene expression across the menstrual cycle
Objective To determine the susceptibility of the endometrium to infection by—and thereby potential damage from—SARS-CoV-2. Design Analysis of SARS-Cov-2 infection-related gene expression from endometrial transcriptomic data sets. Setting Infertility research department affiliated with a public hospital. Patient(s) Gene expression data from five studies in 112 patients with normal endometrium collected throughout the menstrual cycle. Intervention(s) None. Main Outcome Measure(s) Gene expression and correlation between viral infectivity genes and age throughout the menstrual cycle. Result(s) Gene expression was high for TMPRSS4, CTSL, CTSB, FURIN, MX1, and BSG; medium for TMPRSS2; and low for…
Guidelines for biomarker discovery in endometrium: correcting for menstrual cycle bias reveals new genes associated with uterine disorders
Abstract Transcriptomic approaches are increasingly used in reproductive medicine to identify candidate endometrial biomarkers. However, it is known that endometrial progression in the molecular biology of the menstrual cycle is a main factor that could affect the discovery of disorder-related genes. Therefore, the aim of this study was to systematically review current practices for considering the menstrual cycle effect and to demonstrate its bias in the identification of potential biomarkers. From the 35 studies meeting the criteria, 31.43% did not register the menstrual cycle phase. We analysed the menstrual cycle effect in 11 papers (including 12 studies) from Gene Expression Omnibus: t…
Transcriptomic behavior of genes associated with chromosome 21 aneuploidies in early embryo development.
To analyze how chromosome 21 (HSA21) ploidy affects global gene expression of early human blastocysts.Prospective study.University-affiliated in vitro fertilization clinic.A total of 26 high-quality donated embryos from in vitro fertilization (IVF) patients: trisomy 21 (n = 8), monosomy 21 (n = 10), and euploid (n = 8) blastocysts.None.Blastocyst transcriptome changes and its associated functions.Trisomy 21, monosomy 21, and euploid blastocysts were classified by comparative genomic hybridization. The global transcriptome of whole blastocysts was analyzed with small cell number RNA sequencing, and they were compared to understand the gene expression behavior at early development and its imp…
Uterine disorders affecting female fertility: what are the molecular functions altered in endometrium?
[EN]: Objective:To determine the molecular functions of genes exhibiting altered expression in the endometrium of women with uterine disorders affecting fertility. Design: Retrospective analysis integrating case and control data from multiple cohorts with endometrium gene expression in women with uterine disorders. Setting: Infertility research department affiliated with a university hospital. Patient(s): Two hundred and forty women, 121 of whom were controls, 119 of whom had endometrial adenocarcinoma (ADC), recurrent implantation failure (RIF), recurrent pregnancy loss (RPL), or stage II–IV endometriosis. Intervention(s): None. Main Outcome Measure(s): Genomewide gene expression and alter…
Transcriptional changes through menstrual cycle reveal a global transcriptional derepression underlying the molecular mechanism involved in the window of implantation
The human endometrium is a dynamic tissue that only is receptive to host the embryo during a brief time in the middle secretory phase, called the window of implantation (WOI). Despite its importance, regulation of the menstrual cycle remains incompletely understood. The aim of this study was to characterize the gene cooperation and regulation of menstrual cycle progression, to dissect the molecular complexity underlying acquisition of endometrial receptivity for a successful pregnancy, and to provide the scientific community with detailed gene co-expression information throughout the menstrual cycle on a user-friendly web-tool database. A retrospective gene co-expression analysis was perfor…
Analysis of serum and endometrial progesterone in determining endometrial receptivity.
Abstract STUDY QUESTION Is there a relationship between serum and endometrial progesterone (P4) levels, including P4 and metabolites (oestrone, oestradiol and 17α-hydroxyprogesterone), and endometrial receptivity? SUMMARY ANSWER Serum P4 levels were not correlated with endometrial P4, nor associated with endometrial receptivity as determined by the ERA® test; however, endometrial P4 and 17α-hydroxyprogesterone levels were positively correlated and related to endometrial receptivity by ERA. WHAT IS KNOWN ALREADY Acquisition of endometrial receptivity is governed by P4, which induces secretory transformation. A close relationship between serum P4 and pregnancy outcome is reported for hormone …
Asynchronous and pathological windows of implantation: two causes of recurrent implantation failure
STUDY QUESTION: Is endometrial recurrent implantation failure (RIF) only a matter of an asynchronous (displaced) window of implantation (WOI), or could it also be a pathological (disrupted) WOI? SUMMARY ANSWER: Our predictive results demonstrate that both displaced and disrupted WOIs exist and can present independently or together in the same RIF patient. WHAT IS KNOWN ALREADY: Since 2002, many gene expression signatures associated with endometrial receptivity and RIF have been described. Endometrial transcriptomics prediction has been applied to the human WOI in two previous studies. One study describes endometrial RIF to be the result of a temporal displacement of the WOI. The other indic…
Dysregulated genes and their functional pathways in luteinized granulosa cells from PCOS patients after cabergoline treatment
Polycystic ovarian syndrome (PCOS) is a common reproductive disorder frequently associated with a substantial risk factor for ovarian hyperstimulation syndrome (OHSS). Dopamine receptor 2 (D2) agonists, like cabergoline (Cb2), have been used to reduce the OHSS risk. However, lutein granulosa cells (LGCs) from PCOS patients treated with Cb2 still show a deregulated dopaminergic tone (decreased D2 expression and low dopamine production) and increased vascularization compared to non-PCOS LGCs. Therefore, to understand the PCOS ovarian physiology, it is important to explore the mechanisms that underlie syndrome based on the therapeutic effects of Cb2. Here, LGCs from non-PCOS and PCOS patients …