0000000000164406
AUTHOR
José Antonio Martínez-conejero
Is ovarian stimulation detrimental to the endometrium?
Ovarian stimulation in assisted reproduction technology produces lower implantation rates per embryo transferred than natural and ovum donation cycles, suggesting suboptimal endometrial development due to the abnormal concentrations of hormones used to recruit more oocytes. After the publication of several studies on the gene expression profile of endometrial receptivity in the natural cycle using microarray technology, researchers have investigated the impact of ovarian stimulation on the gene expression pattern of the endometrium. Ovarian stimulation cycles that use gonadotrophin-releasing hormone (GnRH) agonists and antagonists have been analysed in detail during the window of implantati…
A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature
Objective: To create a genomic tool composed of a customized microarray and a bioinformatic predictor for endometrial dating and to detect pathologies of endometrial origin. To define the transcriptomic signature of human endometrial receptivity. Design: Two cohorts of endometrial samples along the menstrual cycle were used: one to select the genes to be included in the customized microarray (endometrial receptivity array [ERA]), and the other to be analyzed by ERA to train the predictor for endometrial dating and to define the transcriptomic signature. A third cohort including pathological endometrial samples was used to train the predictor for pathological classification. Setting: Healthy…
Microarray analysis in sperm from fertile and infertile men without basic sperm analysis abnormalities reveals a significantly different transcriptome.
Sperm analysis following World Health Organization guidelines is unable to explain the molecular causes of male infertility when basic sperm parameters are within a normal range and women do not present gynecologic pathology. Consequently, there is a need for accurate diagnostic tools in this area, and microarray technology emerges as promising. We present, for the first time, preliminary results of a comparison of sperm mRNA expression profiles between fertile and infertile men with normal semen parameters, discovering profound discrepancies between groups, with potential diagnostic and therapeutic possibilities.
Endometrial receptivity and implantation are not affected by the presence of uterine intramural leiomyomas: a clinical and functional genomics analysis.
Uterine leiomyomas are the most frequent benign tumors during reproductive age. Whether intramural leiomyomas cause infertility and should be removed is controversial because no study has addressed the underlying mechanism of infertility.The objective of the study was to test the effect of intramural leiomyomas on endometrial function by comparing gene during the window of implantation and implantation in an oocyte donation program, in which the quality of the embryos replaced is similar and the endocrine environment of the endometrium is standardized by exogenous steroids.Human endometria of women with single intramural leiomyomas (group A,5 cm and group B,or =5 cm) and controls (group C) …
Cigarette smoking affects specific sperm oxidative defenses but does not cause oxidative DNA damage in infertile men
Objective To evaluate the effects of tobacco consumption on the oxidative defenses of sperm, the glutathione system (GS), and sperm DNA oxidation. Design Double-blind experimental study. Setting Andrology laboratory in a university-affiliated private setting. Patient(s) One hundred seventeen semen samples from infertile males. Intervention(s) None. Main Outcome Measure(s) (a) sperm GS enzymatic activity with respect to glutathione peroxidase isoforms GPx-1 and GPx-4, glutathione reductase (GR), and cellular glutathione (GSH) content (n = 29); (b) GPx-1, GPx-4, and GR m RNA expression analysis (n = 33); (c) oxidative DNA damage quantification using OXIDNA assay kit (n = 55). Two groups were …
The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity
Objective To compare the accuracy and reproducibility of the endometrial receptivity array (ERA) versus standard histologic methods. Design A comparative prospective study (May 2008–May 2012). Setting University-affiliated infertility clinic. Patient(s) Eighty-six healthy oocyte donors, regularly cycling, aged 20–34 years with a body mass index (BMI) of 19–25 kg/m 2 . Intervention(s) Endometrial biopsies were collected throughout the menstrual cycle. For the accuracy study, 79 samples were grouped into two cohorts: the training set (n = 79) for ERA machine-learning training and dating, and a dating subset (n = 49) for comparison between histologic and ERA dating. For the reproducibility stu…
Modeling Human Endometrial Decidualization from the Interaction between Proteome and Secretome
Context: Decidualization of the human endometrium, which involves morphological and biochemical modifications of the endometrial stromal cells (ESCs), is a prerequisite for adequate trophoblast invasion and placenta formation. Objective: This study aims to investigate the proteome and secretome of in vitro decidualized ESCs. These data were combined with published genomic information and integrated to model the human decidualization interactome. Design: Prospective experimental case–control study. Setting: A private research foundation. Patients: Sixteen healthy volunteer ovum donors. Intervention: Endometrial samples were obtained, and ESCs were isolated and decidualized in vitro. Main Ou…
The transcriptome of spermatozoa used in homologous intrauterine insemination varies considerably between samples that achieve pregnancy and those that do not.
Objective To differentiate transcripts' expression in the sperm from patients who achieved pregnancy in their first IUI cycle from those who did not. Basic sperm analysis is limited to forecasting pregnancies by means of assisted reproduction. New assays, such as microarray analysis, are potential predictive tools for this purpose. Design Nested case-control study. Setting University-affiliated private setting. Patient(s) Twenty sperm samples were obtained from infertile males undergoing their first IUI cycle with healthy partners. Sperm samples with which pregnancy was achieved (P; n=10) and those with which it was not achieved (NP; n=10) were identified and their respective messenger RNA …
Differential transcriptomic profile in spermatozoa achieving pregnancy or not via ICSI
Basic sperm analysis is limited as a method of estimating pregnancy. This study’s objective was use of microarray technology to differentiate the gene expressions of spermatozoa that achieved pregnancy in an intracytoplasmic sperm injection (ICSI)cycle in an oocyte donation programme with those that did not achieve pregnancy. A study of nested cases and controls was designed to evaluate fresh and frozen spermatozoa from infertile males undergoing ICSI with donor oocytes. The global genome expression of pooled samples from each group (achieving pregnancy versus those that didn’t, from fresh or frozen spermatozoa)was compared using microarray analysis. The level of expression of some of the t…
Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome
Objective To determine whether luteal phase endometrial transcriptome is altered in obese women during the window of implantation (WOI), considering the presence of infertility, fat distribution and association with polycystic ovary syndrome (PCOS). Design Prospective study. Setting University-affiliated infertility clinic, between May 2007 and March 2009. Patient(s) One control group of women with normal weight (n = 4), and four study groups of obese women (n = 6 each one) according to the association with infertility, PCOS, and ovarian stimulation. Intervention(s) The endometrium was biopsied 7 days after LH surge or hCG administration in 28 women. Main Outcome Measure(s) Endometrial gene…
Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis
Elevated serum progesterone levels at the end of the follicular phase in controlled ovarian stimulation (COS) leads to a poorer ongoing pregnancy rate in IVF cycles due to reduced endometrial receptivity. The objective of this study was to use microarray technology to compare endometrial gene expression profiles at the window of implantation according to the levels of circulating progesterone.For this prospective cohort study, microarray data were obtained from endometrial biopsies from 12 young healthy oocyte donors undergoing COS with pituitary suppression by either gonadotrophin-releasing hormone (GnRH) agonists or antagonists, and recombinant FSH. On the day of recombinant chorionic gon…
Tecnología BACs-on-Beads™ aplicada al diagnóstico prenatal y al estudio citogenético de restos abortivos
Resumen La tecnologia de BACs-on-Beads utiliza sondas de ADN procedentes de Cromosomas Artificiales Bacterianos o BAC fijados en microesferas Luminex®. La muestra marcada y los ADN de referencia marcados se hibridan respectivamente con las mismas sondas BoBsTM complementarias. Despues de la hibridacion se leen las intensidades de la senal mediante el sistema instrumental Luminex® 100/200. Se puede aplicar al diagnostico prenatal rapido con un kit disenado para descartar aneuploidias para los cromosomas 13, 18, 21 y los cromosomas sexuales asi como ganancias y perdidas de ADN asociadas con 9 sindromes de microdelecion como son: Sindrome de DiGeorge, Sindrome de Williams-Beuren, Sindrome de P…
Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility
Successful embryo implantation depends on the quality of the embryo, as well as on the receptivity of the endometrium. The aim of this study was to investigate the endometrial gene expression profile in women with unexplained infertility in comparison with fertile controls at the time of embryo implantation in order to find potential predictive markers of uterine receptivity and to identify the molecular mechanisms of infertility. High-density oligonucleotide gene arrays, comprising 44 000 gene targets, were used to define the endometrial gene expression profile in infertile (n = 4) and fertile (n = 5) women during the mid-secretory phase (day LH + 7). Microarray results were validated usin…
MUC1 in human testis and ejaculated spermatozoa and its relationship to male fertility status.
MUC1 is a cell surface glycoprotein with a previously described antiadhesive role involved in different aspects of reproductive function. We found MUC1 expressed in male germ cell line and within the ejaculated sperm, but its presence in mature sperm does not seem to be related to male fertility. This was confirmed after analysis of results from assisted reproduction techniques with oocyte donation related with MUC1, although higher MUC1 expression is related to sperm recovery after preparation.
Human Endometrial Side Population Cells Exhibit Genotypic, Phenotypic and Functional Features of Somatic Stem Cells
During reproductive life, the human endometrium undergoes around 480 cycles of growth, breakdown and regeneration should pregnancy not be achieved. This outstanding regenerative capacity is the basis for women's cycling and its dysfunction may be involved in the etiology of pathological disorders. Therefore, the human endometrial tissue must rely on a remarkable endometrial somatic stem cells (SSC) population. Here we explore the hypothesis that human endometrial side population (SP) cells correspond to somatic stem cells. We isolated, identified and characterized the SP corresponding to the stromal and epithelial compartments using endometrial SP genes signature, immunophenotyping and char…
Hormonal and molecular characterization of follicular fluid, cumulus cells and oocytes from pre-ovulatory follicles in stimulated and unstimulated cycles
background: The use of ovarian stimulation, to stimulate a multi-follicular response for assisted reproduction treatments, may force the production of oocytes from follicles that do not reach optimal maturation, possibly yielding oocytes that are not fully competent. The present study aimed to define the follicular environment and oocyte competence of unstimulated pre-ovulatory follicles, to compare it with that of similar-sized stimulated follicles. For this purpose, we analyzed the follicular hormonal milieu, the oocyte meiotic spindle, the embryo development and the cumulus cells gene expression (GE) profiles. methods and results: The study population was divided in two groups: (i) 42 oo…
The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor
Objective: One byproduct resulting from free radical damage is the DNA hydroxylation also known as DNA oxidation. Our aim with this work was to determine the relevance of sperm DNA oxidation on embryo quality in oocyte donation cycles. Design: We prospectively studied pairs of oocyte donation cycles, i.e., the same oocyte donors, donating to two recipients, where the only difference between the two treatments was the use of a different sperm sample. Setting: University-affiliated private IVF setting. Patient(s): Infertile male partners from couples undergoing oocyte donation cycles (n=38): 76 semen aliquots analyzed before and after semen processing by swim up. Intervention(s): None. Main O…
Endometrial Receptivity in Natural and Controlled Ovarian-Stimulated Cycles
The development of endometrial receptivity is a prerequisite for successful embryonic implantation in mammals. The receptive status is reached only during a short period of time in the midluteal phase, this being maximal 7 days after the endogenous peak of LH (LH+7), named as the window of implantation (WOI). At this time, the endometrial epithelium acquires the functional ability to support blastocyst adhesion. In ART, controlled ovarian stimulation (COS) induces lower implantation rates per embryo transferred than natural or ovum donation cycles, suggesting suboptimal endometrial development due to the abnormal endocrine/paracrine milieu. Researchers have investigated the functional genom…