Human Endometrial Reconstitution From Somatic Stem Cells: The Importance of Niche-Like Cells.

Endometrial regeneration has long been proposed to be mediated by stem cells, but the isolation of endometrial stem cells has been hampered by a lack of validated markers. Specific markers would enable isolation of these stem cells, thereby promoting advancements in regenerative medicine for the treatment of endometrial diseases and dysfunctions. We sought to investigate the regenerative ability of human endometrial positive for sushi domain containing 2/intercellular adhesion molecule 1 (SUSD2/ICAM1) cells and Side Population cell lines in a xenograft mice model.

Origin and composition of cell-free DNA in spent medium from human embryo culture during preimplantation development.

Study Question: What is the origin and composition of cell-free DNA in human embryo spent culture media?

Summary Answer: Cell-free DNA from human embryo spent culture media represents a mix of maternal and embryonic DNA, and the mixture can be more complex for mosaic embryos.

What Is Known Already: In 2016, ~300 000 human embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus. While progress in genetic techniques has enabled analysis of the full karyotype in a single cell with high sensitivity and specificity, these approaches still require an embryo biopsy.

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.

Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology.

In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype.

Dynamic expression of PGRMC1 and SERBP1 in human endometrium: an implication in the human decidualization process.

Objective: To characterize PGRMC1 and SERBP1 in human endometrium and to investigate the putative role of PGRMC1 in endometrial decidualization.

Design: The PGRMC1 and SERBP1 expression in human endometrium was determined throughout the menstrual cycle. We analyzed the colocalization of PGRMC1 and SERBP1.

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.

Role of Stro1+/CD44+ stem cells in myometrial physiology and uterine remodeling during pregnancy.

Regulation of myometrial functions during pregnancy has been considered the result of the integration of endocrine and mechanical signals. Nevertheless, uterine regeneration is poorly understood, and the cellular source within the gravid uterus is largely unexplored.In this study, we isolated and quantified the myometrial stem cells (MSC) population from pregnant female Eker rat uteri, by using Stro1/CD44 surface markers.

Lipidomic profiling of endometrial fluid in women with ovarian endometriosis†.

The proteomic content of the endometrial fluid (EF) from patients with endometriosis has been investigated, but the lipidomic profile has not been analyzed yet in detail.This study is a comparative untargeted lipidomic analysis of human EF obtained from 35 patients (12 endometriosis and 23 controls). Global differential lipidomic profile was analyzed in both groups by ultrahigh performance liquid chromatography coupled to mass spectrometry.

Severe pre-eclampsia is associated with alterations in cytotrophoblasts of the smooth chorion.

Pre-eclampsia (PE), which affects ∼8% of first pregnancies, is associated with faulty placentation. Extravillous cytotrophoblasts (CTBs) fail to differentiate properly, contributing to shallow uterine invasion and deficient spiral artery remodeling. We studied the effects of severe PE (sPE) on the smooth chorion portion of the fetal membranes.

A novel homologous model for noninvasive monitoring of endometriosis progression.

To date, several groups have generated homologous models of endometriosis through the implantation of endometrial tissue fluorescently labeled by green fluorescent protein (GFP) or tissue from luciferase-expressing transgenic mice into recipient animals, enabling noninvasive monitoring of lesion signal. These models present an advantage over endpoint models, but some limitations persist; use of transgenic mice is laborious and expensive, and GFP presents poor tissue penetration due to the relatively short emission wavelength. For this reason, a homologous mouse model of endometriosis that allows in vivo monitoring of generated lesions over time and mimics human lesions in recipient mice would be most desirable.

Bioengineering the Uterus: An Overview of Recent Advances and Future Perspectives in Reproductive Medicine.

Since the initial in vitro attempts to more complex models, research on uterine regeneration is moving towards the creation of a functional bioengineered uterus with possible clinical applications. We describe here the most relevant advances in bioengineering of the uterus published in the last decades considering the use of stem cells and biomaterials as well as future developing techniques in Regenerative Medicine.

Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the endometrial stem cell niche.

Objective: To study, isolate and characterize leucine-rich repeat-containing heterotrimeric guanine nucleotide-binding protein-coupled receptor 5 (LGR5)-positive cells from human endometrium to determine their functional relevance.

Design: Prospective experimental animal study.

Setting: University research laboratories.

Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.

Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans.

Detection of Missing Proteins Using the PRIDE Database as a Source of Mass Spectrometry Evidence.

The current catalogue of the human proteome is not yet complete, as experimental proteomics evidence is still elusive for a group of proteins known as the missing proteins. The Human Proteome Project (HPP) has been successfully using technology and bioinformatic resources to improve the characterization of such challenging proteins. In this manuscript, we propose a pipeline starting with the mining of the PRIDE database to select a group of data sets potentially enriched in missing proteins that are subsequently analyzed for protein identification with a method based on the statistical analysis of proteotypic peptides.

Spermatozoa from infertile patients exhibit differences of DNA methylation associated with spermatogenesis-related processes: an array-based analysis.

The influence of aberrant sperm DNA methylation on the reproductive capacity of couples has been postulated as a cause of infertility. This study compared the DNA methylation of spermatozoa of 19 fertile donors and 42 infertile patients using the Illumina 450K array. Clustering analysis of methylation data arranged fertile and infertile patients into two groups.

Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research.

Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality. However, the emergence of personalized medicine in ovulation induction and embryology has shifted the focus to assessing the individual status of the endometrium. The endometrium is considered receptive during an individually defined period, the window of implantation (WOI), when the mother permits a blastocyst to attach and implant.

Endometrial 'scratching': what the data show.

Purpose Of Review: Since its first description in 2003, the endometrial scratching procedure has been the topic of over 1000 studies. This procedure, used to improve endometrial receptivity for assisted reproduction, is accessible - any gynecologist can easily perform it - and has been adapted into clinical routine by some reproductive units. However, the available data are controversial, and no biological plausibility exists to support the use of this intervention.

Impact of vitrification on the mitochondrial activity and redox homeostasis of human oocyte.

Study Question: Do the extreme conditions of vitrification affect mitochondrial health and reactive oxygen species (ROS) levels of human oocytes?

Summary Answer: Vitrification of discarded human oocytes shifts the intracellular redox potential towards oxidation but does not alter the mitochondrial potential or intracellular ROS levels.

What Is Known Already: Recent studies have reflected increased ROS levels in warmed young oocytes and have highlighted the temporal dynamic loss of mitochondrial potential that could, therefore, lead to a decrease in ATP production, impairing embryo development. Mitochondrial function can also be evaluated in vivo by the FAD/NAD(P)H autofluorescence ratio, which reflects the respiratory chain activity and is considered as a marker of the intracellular redox state.

Osmotic-shock produced by vitrification solutions improves immature human oocytes in vitro maturation.

Background: During cytoplasmic oocyte maturation, Ca(2+) currents are vital for regulating a broad range of physiological processes. Recent studies have demonstrated that DMSO and EG cause large transient increases in intracellular Ca(2+) in mouse oocytes. The CP used in vitrifying protocols also increases the intracellular calcium transient.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial.

Study Question: Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation?

Summary Answer: Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival.

What Is Known Already: The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1.

Integrin α4-positive human trophoblast progenitors: functional characterization and transcriptional regulation.

Study Question: What are the functional characteristics and transcriptional regulators of human trophoblast progenitor cells (TBPCs)?

Summary Answer: TBPC lines established from the human smooth chorion by cell sorting for integrin α4 expressed markers of stemness and trophoblast (TB) stage-specific antigens, invaded Matrigel substrates and contributed to the cytotrophoblasts (CTBs) layer of smooth chorion explants with high-mobility group protein HMGI-C (HMGA2) and transcription factor GATA-4 (GATA4) controlling their progenitor state and TB identity.

What Is Known Already: Previously, we reported the derivation of TBPC lines by trypsinization of colonies that formed in cultures of chorionic mesenchyme cells that were treated with an activin nodal inhibitor. Microarray analyses showed that, among integrins, α4 was most highly expressed, and identified HMGA2 and GATA4 as potential transcriptional regulators.

Bacterial and fungal contamination risks in human oocyte and embryo cryopreservation: open versus closed vitrification systems.

Objective: To study the contamination risk in open and closed vitrification devices for oocyte/embryo cryopreservation by evaluating the contaminants present (bacteria and fungi) in the thaw medium and in liquid nitrogen (LN) storage containers.

Design: Retrospective study.

Setting: Human reproduction unit.

Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman's syndrome and endometrial atrophy: a pilot cohort study.

Study Question: Could cell therapy using autologous peripheral blood CD133+ bone marrow-derived stem cells (BMDSCs) offer a safe and efficient therapeutic approach for patients with refractory Asherman's syndrome (AS) and/or endometrial atrophy (EA) and a wish to conceive?

Summary Answer: In the first 3 months, autologous cell therapy, using CD133+ BMDSCs in conjunction with hormonal replacement therapy, increased the volume and duration of menses as well as the thickness and angiogenesis processes of the endometrium while decreasing intrauterine adhesion scores.

What Is Known Already: AS is characterized by the presence of intrauterine adhesions and EA prevents the endometrium from growing thicker than 5 mm, resulting in menstruation disorders and infertility. Many therapies have been attempted for these conditions, but none have proved effective.