Publications by authors named "Jose A Horcajadas"

Purpose: To analyse the effect of ulipristal acetate (UPA) as emergency contraception (EC) on the gene expression of human endometrial cell line (HEC-1A) and endometrium from fertile women treated with UPA after ovulation.

Materials And Methods: HEC-1A cells were treated with UPA, and endometrial tissue from four healthy women was collected in cycles before, during and 2 months after post-ovulation pill intake. Ovulation and luteal phase were monitored, and endometrial biopsies were obtained at day LH + 7 in each cycle.

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Although the concept of precision medicine, in which healthcare is tailored to the molecular and clinical characteristics of each individual, is not new, its implementation in clinical practice has been heterogenous. In some medical specialties, precision medicine has gone from being just a promise to a reality that achieves better patient outcomes. This is a fact if we consider, for example, the great advances made in the genetic diagnosis and subsequent treatment of countless hereditary diseases, such as cystic fibrosis, which have improved the life expectancy of many of the affected children.

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Objective: To study how the attributes of mosaicism identified during preimplantation genetic testing for aneuploidy relate to clinical outcomes, in order to formulate a ranking system of mosaic embryos for intrauterine transfer.

Design: Compiled analysis.

Setting: Multi-center.

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Intrauterine devices (IUDs) have been widely used to prevent pregnancies with great efficacy during decades. It has been demonstrated that IUD alters the endometrial gene expression, but there is no scientific data about how copper, a metal commonly used in these devices, by itself, is able to influence the processes of endometrial receptivity and apoptosis in decidualized human endometrial stromal cells. Five endometrial samples were obtained from fertile women and processed by a standard protocol to obtain human endometrial stromal cells for in vitro studies.

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Article Synopsis
  • Scientists are trying to find the best way to prepare the lining of the uterus (endometrium) for frozen embryo transfers, especially for women who have had trouble getting pregnant.
  • They studied 15 endometrial samples to compare two methods: natural cycles and artificial cycles, to see which one helps with implantation better.
  • Results showed that natural cycles are better for preparing the endometrium, while artificial cycles might hurt the body’s ability to get ready for the embryo, affecting important genes related to pregnancy.
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Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear.

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Objective: To characterize the transcriptome of luminal epithelia (LE) of fertile secretory endometria and compare the results with those from glandular epithelia (GE).

Design: Endometrial samples were collected at 2 and 7 days after initial blood LH surge in separate menstrual cycles. LE were obtained with the use of laser microdissection.

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Purpose: To identify the secreted proteins of murine embryos grown in vitro.

Methods: Two-cell mouse embryos (n=432) were randomly allocated to culture to the blastocyst stage in protein-free and in protein-supplemented (3 % BSA) media. Proteins were separated by SDS-PAGE; bands were visualized by coomassie staining, followed by in-gel trypsin digestion and liquid chromatography-tandem mass spectrometry.

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Background: 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field.

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MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women.

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Objective: To map the changes in messenger RNA (mRNA) and protein abundance during the window of implantation in specifically endometrial stromal and glandular epithelial cells obtained using laser microdissection microscopy (LDM).

Design: Endometrial samples were collected from two menstrual cycles at 2 and 7 days after first significant rise in blood LH, and separate cell populations were obtained using LDM. A new generation linear polymerase chain reaction (PCR) amplified the mRNA, which were hybridized to both Affymetrix U133 Plus2 and Agilent 4x44K microarrays followed by gene set analysis.

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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.

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There is an urgent need to develop optimized experimental models to examine human implantation. These studies aimed to (i) establish a human endometrium-like three-dimensional (3D) culture system, and (ii) examine the attachment of trophoblast-like Jar spheroids to the culture. In the present work, 3D endometrial cultures were constructed with fibrin-agarose as matrix scaffold, and using epithelial and stromal cells from both human primary cultures and established cell lines.

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Microarray technology was used to explore differences in brain gene expression under basal conditions in two strains of psychogenetically selected rats which differ in anxiety/stress responses, the inbred Roman High-(RHA-I) and Roman Low-(RLA-I) Avoidance rats. Microarray analysis detected 14 up-regulated and 24 down-regulated genes in RLA-I vs. RHA-I rats functionally related to neurobiological processes.

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Objective: To evaluate the effect of adenomyosis on endometrial gene expression and its correlation with clinical outcome.

Design: Transcriptomic analysis of the endometrium of women with adenomyosis during the window of implantation. Retrospective matched cohort study of the impact of adenomyosis on oocyte donation (OD) outcome.

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Article Synopsis
  • The study aimed to find out how obesity affects the genes in the endometrium (the lining of the uterus) during a crucial time for implantation in women.
  • Researchers compared normal-weight women with groups of obese women who had different issues like infertility or polycystic ovary syndrome (PCOS).
  • The results showed that many genes in obese women were different from those in normal-weight women, especially when they had infertility, which could affect their ability to get pregnant.
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Identification of genes involved in trophoblast differentiation is of great interest in understanding cellular and molecular mechanisms involved in placental development and is relevant clinically to fetal development, fertility, and maternal health. Herein, we investigated differentiation of human embryonic stem cells (hESCs) down the trophoblast lineage by culture with bone morphogenetic protein 4 (BMP4) over a 10-day period. Within 2 days, the stemness markers POU5F1 and NANOG were markedly down-regulated, followed temporally by up-regulation of the CDX2, KRT7, HLA-G, ID2, CGA, and CGB trophoblast markers.

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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.

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Article Synopsis
  • The human endometrium experiences about 480 cycles of growth and regeneration throughout reproductive life, relying on somatic stem cells (SSC) for this process.
  • Researchers hypothesize that specific endometrial side population (SP) cells act as somatic stem cells, isolating and characterizing these cells from both stromal and epithelial areas using various techniques.
  • The study demonstrated that endometrial SP cells possess the ability to differentiate into other cell types and can regenerate endometrial tissue when injected into mice, indicating their potential role in endometrial repair.
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The cellular sources that contribute to the renewal of human endometrium are largely unknown. It has been suggested that endometrial stem cells originate from bone marrow-derived mesenchymal stem cells (MSC), with subsequent development into endometrial stromal fibroblasts (hESF). We hypothesized that if bone marrow-derived MSC contribute to endometrial regeneration and are progenitors of hESF, their treatment with agents known to regulate hESF differentiation could promote their differentiation down the stromal fibroblast lineage.

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Intrinsic abnormalities in transplanted eutopic endometrium are believed to contribute to the pathogenesis of pelvic endometriosis. Herein we investigated transcriptomic differences in human endometrial stromal fibroblasts (hESFs) from women with (hESF(endo)) vs. without (hESF(nonendo)) endometriosis, in response to activation of the protein kinase A (PKA) pathway with 8-bromoadenosine-cAMP (8-Br-cAMP).

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Context: Controlled ovarian stimulation induces morphological, biochemical, and functional genomic modifications of the human endometrium during the window of implantation.

Objective: Our objective was to compare the gene expression profile of the human endometrium in natural vs. controlled ovarian stimulation cycles throughout the early-mid secretory transition using microarray technology.

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Context: 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.

Objective: 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.

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Background: New approaches for non-invasive embryo-quality assessment are among the major goals in Reproductive Medicine. We hypothesize that the detection of changes in the protein profile of the culture media in which blastocysts are cultured could be a potential indicator of the viability of the embryo and, thus, a useful tool for selecting the more appropriate blastocysts to be transferred.

Methods: Using protein-array technology, we analysed the protein profile corresponding to 24 h conditioned media of blastocysts that implanted versus those that did not implant.

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Controlled ovarian stimulation (COS) is widely used in assisted reproduction techniques (ART). However, hormonal treatment induces endometrial alterations that may alter implantation rates compared with natural cycles. Endometrial alterations have been observed by histological and biochemical techniques.

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