Mother and Embryo Cross-Communication

Idelevich, Anna; Vilella, Felipe

doi:10.3390/genes11040376

Cited by 38 publications

(28 citation statements)

References 101 publications

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“…RIF can be a consequence of embryo-related factors, oocyte or sperm quality, parental chromosomal anomalies, uterine factors, immunological factors, and thrombophilic conditions [ 5 ]. The embryo itself is thought to be responsible for 30–50% of RIF [ 6 , 7 ]. The transfer of chromosomally anomalous embryos will result in failed implantation.…”

Section: Introductionmentioning

confidence: 99%

Next-Generation Sequencing (NGS)-Based Preimplantation Genetic Testing for Aneuploidy (PGT-A) of Trophectoderm Biopsy for Recurrent Implantation Failure (RIF) Patients: a Retrospective Study

et al. 2021

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Recurrent implantation failure (RIF) is an intrigue condition during in vitro fertilization (IVF) cycles or intracytoplasmic sperm injection (ICSI) treatments. The purpose of this retrospective study is to explore the value of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) of trophectoderm biopsy in the clinical outcomes for RIF patients with advanced age. A total of 265 RIF patients, who underwent 346 oocyte retrieval cycles and 250 PGT-A cycles, were classified as two groups according to the female age, including < 38 and ≥ 38 years old groups. The two groups were statistically comparable in baseline characteristics. The component of aneuploid embryos was significantly higher in advanced age group than in younger age group (68.9 vs 39.9%, P < 0.001). But there were no statistically significant differences in pregnancy rate (43.5 vs 64.7%), clinical pregnancy rate (39.1 vs 48.0%), implantation rate (39.1 vs 51.0%), and miscarriage rate (4.3 vs 7.8%) per embryo transfer (ET) between the two groups. Results suggest that the embryo-related factor plays a crucial role in RIF. Maternal age does not influence the implantation potential of euploid blastocysts. The NGS-based PGT-A involving trophectoderm biopsy is valuable for RIF patients of advanced age by improving their clinical outcomes. In conclusion, the NGS-based PGT-A involving trophectoderm biopsy may represent a valuable supplement to the current RIF management. Nonetheless, these findings should be further validated in a well-designed randomized controlled trial.

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Section: Introductionmentioning

confidence: 99%

Next-Generation Sequencing (NGS)-Based Preimplantation Genetic Testing for Aneuploidy (PGT-A) of Trophectoderm Biopsy for Recurrent Implantation Failure (RIF) Patients: a Retrospective Study

et al. 2021

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“…Given that gamete/embryo-maternal communication has been defined as a determinant of reproductive success in many species, including human [ 10 ], studying the role of EVs present in reproductive biological fluids (follicular, oviductal, uterine fluids) has become a hot topic in the last few years [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Extracellular vesicles identified in the oviduct and in the uterus of different species have emerged as key mediators of the early reproductive events contributing to successful pregnancy [ 19 , 20 , 21 ] and as potential biomarkers of reproductive health and disease [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Equine Uterine Extracellular Vesicles: A Comparative Methodological Study

Almiñana

Vegas

Tekin

et al. 2021

IJMS

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Extracellular vesicles (EVs) have been identified in the uterine fluid in different species and have been pointed as key players in the embryo-maternal dialogue, maternal recognition of pregnancy and establishment of pregnancy. However, little is known about the uterine EVs in the mare. Therefore, the present study aimed at characterizing EVs from uterine lavage of cyclic mares by comparing five EVs isolation methods and the combination of them: (1) ultracentrifugation (UC); (2) concentration of lavage volume by Centricon ultrafiltration (CE); (3) the use of CE with different washing steps (phosphate-buffered saline with or without trehalose); (4) size-exclusion chromatography with iZON-qEV columns, and (5) a combination of the methods with best results based on EVs yield, purity, and protein cargo profiles. Transmission electron microscopy and Western blotting confirmed the isolation of EVs by all methods but with quantitative and qualitative differences. Mass spectrometry provided differences in protein profiles between methods, number of identified proteins, and protein classes. Our results indicate that the combination of CE/trehalose/iZON/UC is an optimal method to isolate equine uterine EVs with good yield and purity that can be applied in future studies to determine the role of equine uterine EVs in embryo-maternal interactions.

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“…The luminal epithelium is perceived as the fundamental site for endometrial receptivity ( Idelevich and Vilella, 2020 ), and integrin αVβ3 is a cell-surface adhesion receptor that appears on the apex of endometrial luminal epithelial cell surfaces, coincident with the ‘window of implantation’, and has putative roles in embryo attachment during implantation ( Rai et al , 1996 ; Apparao et al , 2001 ; Lessey, 2002 ; Lessey and Castelbaum, 2002 ). Integrin αVβ3 is maximally expressed during the ‘window of implantation’ ( Apparao et al , 2001 ), and its endometrial expression is significantly lower in cases of unexplained infertility, indicating that aberrant epithelial integrin αVβ3 expression may be associated with defective endometrial receptivity ( Elnaggar et al , 2017 ).…”

Section: Discussionmentioning

confidence: 99%

A 3D endometrial organotypic model simulating the acute inflammatory decidualisation initiation phase with epithelial induction of the key endometrial receptivity marker, integrin αVβ3

Fraser

Smith

Lin

2021

Human Reproduction Open

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STUDY QUESTION Is it possible to develop a simplified physiological in vitro system representing the key cell-types associated with a receptive endometrial phenotype? SUMMARY ANSWER We present a new concept to investigate endometrial receptivity, with a 3D organotypic co-culture model to simulate an early and transient acute autoinflammatory decidual status that resolves in the induction of a receptive endometrial phenotype. WHAT IS KNOWN ALREADY Embryo implantation is dependent on a receptive uterine environment. Ovarian steroids drive post-ovulation structural and functional changes in the endometrium, which becomes transiently receptive for an implanting conceptus, termed the ‘window of implantation’, and dysregulation of endometrial receptivity is implicated in a range of reproductive, obstetric, and gynaecological disorders and malignancies. The interactions that take place within the uterine microenvironment during this time are not fully understood, and human studies are constrained by a lack of access to uterine tissue from specific time-points during the menstrual cycle. Physiologically relevant in vitro model systems are therefore fundamental for conducting investigations to better understand the cellular and molecular mechanisms controlling endometrial receptivity. PARTICIPANTS/MATERIALS, SETTING, METHODS An endometrial stromal cell (ESC) line, and endometrial epithelial cells (EECs) isolated from uterine biopsy tissue and expanded in vitro by conditional reprogramming, were used throughout the study. Immunocytochemical and flow cytometric analyses were used to confirm epithelial phenotype following conditional reprogramming of EECs. To construct an endometrial organotypic co-culture model, ESCs were embedded within a 3D growth factor-reduced Matrigel structure, with a single layer of conditionally reprogrammed EECs seeded on top. Cells were stimulated with increasing doses of medroxyprogesterone acetate, cAMP and estradiol, in order to induce ESC decidual transformation and endometrial receptivity. Decidual response and the induction of a receptive epithelial phenotype were assessed by immunocytochemical detection and quantitative in-cell western analyses, respectively. MAIN RESULTS AND THE ROLE OF CHANCE A transient upregulation of the IL-33 receptor protein, ST2L, was observed in ESCs, indicating a transient autoinflammatory decidual response to the hormonal stimulation, known to induce receptivity gene expression in the overlying epithelium. Hormonal stimulation increased the EEC protein levels of the key marker of endometrial receptivity, integrin αVβ3 (n = 8; *P <0.05; ***P < 0.0001). To our knowledge, this is the first demonstration of a dedicated endometrial organotypic model, that has been developed to investigate endometrial receptivity, via the recapitulation of an early decidual transitory acute autoinflammatory phase and induction of an epithelial phenotypic change, to represent a receptive endometrial status. LIMITATIONS, REASONS FOR CAUTION This simplified in vitro ESC-EEC co-culture system may be only partly representative of more complex in vivo conditions. WIDER IMPLICATIONS OF THE FINDINGS The 3D endometrial organotypic model presented here may offer a valuable tool for investigating a range of reproductive, obstetric, and gynaecological disorders, to improve outcomes for assisted reproductive technologies, and for the development of advances in contraceptive methods. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by an MRC Centre Grant (project reference MR/N022556/1). RF was the recipient of a Moray Endowment award and a Barbour Watson Trust award. C-JL is a Royal Society of Edinburgh Personal Research Fellow, funded by the Scottish Government. The authors have no conflicts of interest to declare.

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Mother and Embryo Cross-Communication

Cited by 38 publications

References 101 publications

Next-Generation Sequencing (NGS)-Based Preimplantation Genetic Testing for Aneuploidy (PGT-A) of Trophectoderm Biopsy for Recurrent Implantation Failure (RIF) Patients: a Retrospective Study

Next-Generation Sequencing (NGS)-Based Preimplantation Genetic Testing for Aneuploidy (PGT-A) of Trophectoderm Biopsy for Recurrent Implantation Failure (RIF) Patients: a Retrospective Study

Isolation and Characterization of Equine Uterine Extracellular Vesicles: A Comparative Methodological Study

A 3D endometrial organotypic model simulating the acute inflammatory decidualisation initiation phase with epithelial induction of the key endometrial receptivity marker, integrin αVβ3

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