Spatial multiomics map of trophoblast development in early pregnancy

Nature, Journal Year: 2023, Volume and Issue: 616(7955), P. 143 - 151

Published: March 29, 2023

Abstract The relationship between the human placenta—the extraembryonic organ made by fetus, and decidua—the mucosal layer of uterus, is essential to nurture protect fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate decidua, transforming maternal arteries into high-conductance vessels 1 . Defects in invasion arterial transformation established early pregnancy underlie common disorders such as pre-eclampsia 2 Here we have generated a spatially resolved multiomics single-cell atlas entire maternal–fetal interface including myometrium, which enables us resolve full trajectory differentiation. We used this cellular map infer possible transcription factors mediating EVT show that they are preserved vitro models differentiation primary organoids 3,4 stem 5 define transcriptomes final cell states invasion: bed giant (fused multinucleated EVTs) endovascular EVTs (which form plugs inside arteries). predict cell–cell communication events contributing formation, model dual role interstitial Together, our data provide comprehensive analysis postimplantation can be inform design experimental placenta

Language: Английский

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Good practice recommendations on add-ons in reproductive medicine

Human Reproduction, Journal Year: 2023, Volume and Issue: 38(11), P. 2062 - 2104

Published: Sept. 25, 2023

Abstract STUDY QUESTION Which add-ons are safe and effective to be used in ART treatment? SUMMARY ANSWER Forty-two recommendations were formulated on the use of diagnosis fertility problems, IVF laboratory clinical management treatment. WHAT IS KNOWN ALREADY The innovative nature combined with extremely high motivation patients has opened door wide application what become known as ‘add-ons’ reproductive medicine. These supplementary options available addition standard procedures, typically incurring an additional cost. A diverse array is made available, encompassing tests, drugs, equipment, complementary or alternative therapies, surgical interventions. share common aim stating enhance pregnancy live birth rates, mitigate risk miscarriage, expedite time achieving pregnancy. DESIGN, SIZE, DURATION ESHRE aimed develop clinically relevant evidence-based focusing safety efficacy currently procedures order improve quality care for infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS appointed a European multidisciplinary working group consisting practising clinicians, embryologists, researchers who have demonstrated leadership expertise research Patient representatives included group. To ensure that guidelines evidence-based, literature identified from systematic search was reviewed critically appraised. In absence any clear scientific evidence, based professional experience consensus thus best evidence expert agreement. Prior publication, by 46 independent international reviewers. total 272 comments received incorporated where relevant. MAIN RESULTS AND THE ROLE OF CHANCE 42 three sections; diagnostic tests interventions, management. LIMITATIONS, REASONS FOR CAUTION Of recommendations, none could high-quality only four moderate-quality implicating 95% supported low-quality randomized controlled trials, observational data, experience, development WIDER IMPLICATIONS FINDINGS offer valuable direction healthcare professionals responsible undergoing treatment Their purpose promote treatment, enabling make informed decisions realistic expectations. fully about various them likelihood test chance birth. FUNDING/COMPETING INTEREST(S) All costs relating process covered funds. There no external funding manuscript production. K.L. reports speakers fees Merck part study Vitrolife (unpaid). T.E. consulting Gynemed, Gynemed advisory board Hamilton Thorne. N.P.P. grants Serono, Ferring Pharmaceutical, Theramex, Gedeon Richter, Organon, Roche, IBSA Besins Healthcare, Healthcare. S.R.H. declares being managing director Fertility Europe, not-for-profit organization receiving financial support ESHRE. I.S. advisor stock Alife Health, co-founder IVFvision LTD (unpaid) speakers’ fee 2023 Young Leader Prestige workshop China. A.P. Pharmaceuticals A/S, Preglem, Novo Nordisk, Pharmaceuticals, Cryos Theramex travel Richter. other authors disclosed conflicts interest. DISCLAIMER This Good Practice Recommendations (GPRs) document represents views ESHRE, which result between stakeholders at preparation. GPRs should information educational purposes. They not interpreted setting bedeemedinclusive all proper methods care, exclusive reasonably directed obtaining same results.Theydo replace need judgement each individual presentation, variations locality facility type. Furthermore, do constitute imply endorsement, favouring, technologies

Language: Английский

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Human embryo implantation

Development, Journal Year: 2023, Volume and Issue: 150(10)

Published: May 15, 2023

Embryo implantation in humans is interstitial, meaning the entire conceptus embeds endometrium before placental trophoblast invades beyond uterine mucosa into underlying inner myometrium. Once implanted, embryo survival pivots on transformation of an anti-inflammatory bed, termed decidua, under homeostatic control natural killer cells. Here, we examine evolutionary context and elaborate remodelling after conception humans. We also discuss interactions between decidualising that regulate interstitial determine fitness. Together, this Review highlights precarious but adaptable nature process.

Language: Английский

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Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(2), P. 181 - 195.e9

Published: Jan. 17, 2024

In humans, balanced invasion of trophoblast cells into the uterine mucosa, decidua, is critical for successful pregnancy. Evidence suggests that this process regulated by natural killer (uNK) cells, but how they influence reproductive outcomes unclear. Here, we used our organoids and primary tissue samples to determine uNK affect placentation. By locating potential interaction axes between using single-cell transcriptomics in vitro modeling these interactions organoids, identify a cell-derived cytokine signal promotes differentiation at late stage invasive pathway. Moreover, it affects transcriptional programs involved regulating blood flow, nutrients, inflammatory adaptive immune responses, as well gene signatures associated with disorders pregnancy such pre-eclampsia. Our findings suggest mechanisms on optimal immunological enhance success.

Language: Английский

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Placenta: an old organ with new functions

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 19, 2024

The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced placenta as major anatomical site provide nutrients, gases, hormones developing fetus. has endocrine functions, orchestrates maternal adaptations pregnancy at different periods pregnancy, acts a selective barrier minimize exposure fetus xenobiotics, pathogens, parasites. Despite fact that this ancient organ is central for normal in eutherians, remains one least studied organs. first step embryo implantation, finely regulated by trophoectoderm, precursor all trophoblast cells. There bidirectional communication between endometrium leading decidualization, critical maintenance pregnancy. are three-direction interactions placenta, immune cells, adaptation endometrial system allogeneic While 65% systemically expressed human proteins have been found tissues, it expresses numerous placenta-specific proteins, whose expression dramatically changed gestational diseases could serve biomarkers early detection diseases. Surprisingly, placentation carcinogenesis exhibit shared features metabolism cell behavior, molecular signatures, signaling pathways, tissue microenvironment, which proposes concept "cancer ectopic trophoblastic cells". By extensive researches novel field, handful cancer discovered. This review paper, inspired part our experiences during past couple years, highlights new aspects placental functions with emphasis on its immunomodulatory role successful potential link carcinogenesis.

Language: Английский

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The human placenta: new perspectives on its formation and function during early pregnancy

Proceedings of the Royal Society B Biological Sciences, Journal Year: 2023, Volume and Issue: 290(1997)

Published: April 18, 2023

The placenta has evolved to support the development of embryo and fetus during different intrauterine periods life. By necessity, its must precede that embryo. There is now evidence embryogenesis organogenesis, human supported by histotrophic nutrition secreted from endometrial glands rather than maternal blood. These secretions provide a plentiful supply glucose, lipids, glycoproteins growth factors stimulate rapid proliferation differentiation villous trophoblast. Furthermore, gland organoids indicates expression secretion these products are upregulated following sequential exposure oestrogen, progesterone trophoblastic decidual hormones, in particular prolactin. Hence, feed-forward signalling dialogue proposed among trophoblast, decidua enables own development, independent Many common complications pregnancy represent spectrum disorders associated with deficient trophoblast proliferation. Increasing suggests this mirrored one impaired decidualization, potentially compromising histotroph through diminished prolactin reduced function. Optimizing wellbeing prior conception may therefore help prevent complications, such as miscarriage, restriction pre-eclampsia.

Language: Английский

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Climate change and pregnancy complications: From hormones to the immune response

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: April 5, 2023

Pregnant women are highly vulnerable to adverse environments. Accumulating evidence highlights that increasing temperatures associated with the ongoing climate change pose a threat successful reproduction. Heat stress caused by an increased ambient temperature can result in pregnancy outcomes, e.g. , preterm birth, stillbirth and low fetal weight. The pathomechanisms through which heat interferes maintenance still remain vague, but emerging underscores endocrine system is severely affected. It well known pivotally contributes physiological progression of pregnancy. We review – sometimes speculate - how offset hormonal dysregulations subsequently derail other systems interact hormones, such as immune response. This may account for heat-stress related progression, development long-term children’s health.

Language: Английский

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The human placenta shapes the phenotype of decidual macrophages

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111977 - 111977

Published: Jan. 1, 2023

lo , have a specific transcriptome, and proliferate in situ d decBAMs are inefficient APCs, induce Tregs, secrete IL-

Language: Английский

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Clinical application and prospect of immune checkpoint inhibitors for CAR-NK cell in tumor immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 19, 2023

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR genetically engineered to express certain molecules, it retains the intrinsic ability recognize through its own receptors. Additionally, NK do not depend on T cell receptors for cytotoxic killing. CAR-NK exhibit some differences CAR-T terms more precise killing, numerous sources, and increased effectiveness solid tumors. However, problems still exist with therapy, such as cytotoxicity, low transfection efficiency, storage issues. Immune checkpoints inhibit immune from performing their normal killing function, clinical application checkpoint inhibitors cancer treatment has become a key therapeutic strategy. The being evaluated ongoing basic studies. may affect function therapy. In this review, we describe combination existing technology therapy discuss future treatments. We also summarize progress trials

Language: Английский

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Progestogen-driven B7-H4 contributes to onco-fetal immune tolerance

Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4713 - 4732.e19

Published: July 4, 2024

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human types the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune checkpoint. We showed that genetic deficiency of resulted activation fetal resorption allogeneic pregnancy models. Analogously, contributed to MPA/DMBA-induced breast progression, accompanied by CD8

Language: Английский

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