Project description:The developmental origins of adult disease are now recognized to reflect intrauterine conditions during embryonic and fetal life. Cell-cell communication between the maternal endometrium and the pre-implantation embryo can occur by several means. Here, we show that maternal miRNAs are secreted by the endometrial epithelium to the endometrial fluid. Microarray assessments revealed the presence of specific miRNAs that are associated with the window of implantation and therefore in direct contact with the human preimplantation embryo. These miRNAS are transported as free or exosome-associated molecules secreted to the endometrial fluid and then uptake into the pre-implantation embryo through the trophoectoderm. Finally, these maternal miRNAsS were able to induce transcriptional and functional modifications of the embryo. Therefore, we propose an innovative model whereby endometrial maternal miRNAS may function as transcriptomic regulators during early embryo development offering a new perspective on the developmental origins of adult diseases such as obesity, type 2 diabetes, and others that are now recognized to reflect intrauterine conditions. This is a prospective study in which endometrial fluid was obtained from healthy patients that had no underlying endometrial pathology and had regular menstrual cycles of between 25 and 33 days. None of these women had received a hormonal preparation in the 3 months preceding biopsy (fluid) collection. Endometrial (fluid) samples were distributed in five groups according to the phase in the cycle: group 1, Early Proliferative (EP) (days 1M-bM-^@M-^S8); group 2, Late Proliferate (LP) (days 9M-bM-^@M-^S14); group 3, Early Secretory (ES) (days 15M-bM-^@M-^S18); group 4, Window of Implantation (WOI) (days 19M-bM-^@M-^S22); and group 5, Late Secretory (LS) (days 23M-bM-^@M-^S28) according to the criteria of Noyes {Noyes:1975vl}. A total of 20 patients were included, four per group
Project description:Ineffective endometrial matrix remodeling, a key factor in infertility, impedes embryo implantation in the uterine wall. Our study reveals the cellular and molecular impact of human collagenase-1 administration in mouse uteri, demonstrating enhanced embryo implantation rates. Collagenase-1 promotes remodeling of the endometrial extracellular matrix (ECM), degrading collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors, (e.g. VEGF, decorin), facilitating vascular permeability and angiogenesis. Collagenase-1 elevates embryo implantation regulators, including NK cell infiltration and the key cytokine LIF. Remarkably, uterine tissue maintains structural integrity despite reduced endometrial collagen fiber tension. In-utero collagenase-1 application rescues implantation in the heat stress and embryo transfer models, known for low implantation rates. Importantly, ex-vivo exposure of human uterine tissue to collagenase-1 induces collagen de-tensioning and VEGF release, mirroring remodeling observed in mice. Our research highlights collagenase potential to induce and orchestrate cellular and molecular processes enhancing uterine receptivity for effective embryo implantation. This innovative approach underscores ECM remodeling mechanisms critical for embryo implantation
Project description:The bovine endometrium secretes proteins during early pregnancy that vary (in both protein identity and abundance) to be in synchrony with luminal reproductive events. To uncover the identity of these proteins, transcriptomics was performed to understand the secretory capability of the bovine endometrium through the distinct phases of early pregnancy in virgin heifers. This dataset should serve as a baseline for understanding the profile of luminal secretory outputs during early pregnancy, setting the stage for functional interpretation of how the uterus supports and directs biological events ranging from sperm transport to preimplantation embryo development.
Project description:Inner uterine lining or endometrium is a unique constantly self-renewed adult tissue that is vital for embryo implantation. As the footrace for universal endometrial receptivity markers continues, RNA-seq remains the most powerful tool for transcriptomic marker discovery. In this study, we aimed to elucidate endometrial maturation mechanisms at transcriptomic level and identify novel robust biomarker candidates for endometrial receptivity in a multicentre study. Additionally, we compared mid-secretory transcriptome profiles from healthy women with profiles of women with repeated IVF failure to find transcriptome changes related to problems with endometrial receptivity.
Project description:Implantation is the attachment of embryo in the endometrium. Failure in implantation is a major cause of early pregnancy loss. During implantation, the temporal uterine lumen closure can help embryo attach to the uterus. In pigs, extending of endometrial folds to form interlocking finger-like projections is a main cause leads to uterine lumen closure during attachment time, but the underlying mechanisms are largely unknown. Our data reveal that pig uterine luminal epithelium (LE) migrate in coordinated groups during extending of endometrial folds. Moreover, the MALDI-TOF MS based N-glycomic characterization of porcine endometrium revealed α2,6-linked sialic acid are highly expressed in pig uterine LE during extending of endometrial folds. To investigated the mechanisms by which α2,6-sialylated proteins in formation of the endometrial folding during implantation in pigs, the α2,6-sialylated proteins in pig uterine LE were characterized by proteomic analysis and those proteins that are involved in cell adhesion, such as E-cadherin, were detected. Finally, our in vivo and in vitro data show that α2,6-sialylation of E-cadherin occurs in accompany with collective epithelial migration. The results provide new insight into the mechanism of pig implantation by identifying that α2,6-sialylation of cell adhesion molecules may participate in formation of extending of endometrial folds through promoting of collective migration of uterine LE.
Project description:The bovine endometrium secretes proteins across the estrous cycle that vary (in both protein identity and abundance) to be in synchrony with luminal reproductive events. To uncover the identity of these proteins, transcriptomics was performed to understand the secretory capability of the bovine endometrium through the distinct phases of the estrous cycle in cows. This dataset should serve as a baseline for understanding the profile of luminal secretory outputs across the estrous cycle, setting the stage for functional interpretation of how the uterus supports and directs biological events ranging from sperm transport to preimplantation embryo development.
Project description:In both beef and dairy cattle, the majority of embryo loss occurs in the first 14 days following insemination. During this period, the embryo is completely dependent on its maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to embryo survival. We used microarrays to assess endometrial gene expression in high and low fertility heifers during the mid-luteal phase of the estrous cycle. Charlaois × Limousin heifers were artificially inseminated on 4 successive occasions and heifers were subsequently characterized as either high or low fertility (HF; LF) based on the presence of an embryo on day 28 of pregnancy on all four inseminations or on one occasion only, respectively. From this population of animals, HF and LF heifers were slaughtered on day 7 of a synchronized estrous cycle and global gene expression in uterine endometrial tissue was determined using the Affymetrix 23K Bovine GeneChip.
Project description:In both beef and dairy cattle, the majority of embryo loss occurs in the first 14-16 days following insemination. During this period, the embryo is completely dependent on its maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to embryo survival. We used microarrays to assess endometrial gene expression in high and low fertility heifers during the late-luteal phase of the estrous cycle. Charlaois M-CM-^W Limousin heifers were artificially inseminated on 4 successive occasions and heifers were subsequently characterized as either high or low fertility (HF; LF) based on the presence of an embryo on day 28 of pregnancy on all four inseminations or on one occasion only, respectively. From this population of animals, HF and LF heifers were slaughtered on day 14 of a synchronized estrous cycle and global gene expression in uterine endometrial tissue was determined using the AffymetrixM-BM-. 23K Bovine GeneChip. Array Annotation link: http://mad-db.science.uva.nl/~wdeleeuw/HybridAnnot/