Association between frailty and subsequent disability trajectories among older adults: a growth curve longitudinal analysis from the Survey of Health, Ageing and Retirement in Europe (2004-19).

Frailty is associated with adverse health outcomes in ageing populations, yet its long-term effect on the development of disability is not well defined. The study examines to what extent frailty affects disability trajectories over 15 years in older adults aged 50+. Using seven waves of data from the Survey of Health, Ageing and Retirement in Europe (SHARE), the study estimates the effect of baseline frailty on subsequent disability trajectories by multilevel growth curve models. The sample included 94 360 individuals from 28 European countries. Baseline frailty was assessed at baseline, using the sex-specific SHARE-Frailty-Instrument (SHARE-FI), including weight loss, exhaustion, muscle weakness, slowness, and low physical activity. Disability outcomes were the sum score of limitations in activities of daily living (ADL) and Instrumental ADL (IADL). Analyses were stratified by sex. Over 15 years, baseline frailty score was positively associated with disability trajectories in men [ßADL = 0.074, 95% confidence interval (CI) = 0.064; P = .083; ßIADL = 0.094, 95% CI = 0.080; P = 0.107] and women (ßADL = 0.097, 95% CI = 0.089; P = .105; ßIADL = 0.108, 95% CI = 0.097; P = .118). Frail participants showed higher ADL and IADL disability levels, independent of baseline disability, compared with prefrail and robust participants across all age groups. Overall, participants displayed higher levels of IADL disability than ADL disability. Study findings indicate the importance of early frailty assessment using the SHARE-FI in individuals 50 and older as it provides valuable insight into future disability outcomes.

Hypoxia and loss of GCM1 expression prevents differentiation and contact inhibition in human trophoblast stem cells.

The placenta develops alongside the embryo and nurtures fetal development to term. During the first stages of embryonic development, due to low blood circulation, the blood and ambient oxygen supply is very low (∼1-2% O 2 ) and gradually increases upon placental invasion. While a hypoxic environment is associated with stem cell self-renewal and proliferation, persistent hypoxia may have severe effects on differentiating cells and could be the underlying cause of placental disorders. We find that human trophoblast stem cells (hTSC) thrive in low oxygen, whereas differentiation of hTSC to trophoblast to syncytiotrophoblast (STB) and extravillous trophoblast (EVT) is negatively affected by hypoxic conditions. The pro-differentiation factor GCM1 (human Glial Cell Missing-1) is downregulated in low oxygen, and concordantly there is substantial reduction of GCM1-regulated genes in hypoxic conditions. Knockout of GCM1 in hTSC caused impaired EVT and STB formation and function, reduced expression of differentiation-responsive genes, and resulted in maintenance of self-renewal genes. Treatment with a PI3K inhibitor reported to reduce GCM1 protein levels likewise counteracts spontaneous or directed differentiation. Additionally, chromatin immunoprecipitation of GCM1 showed enrichment of GCM1-specific binding near key transcription factors upregulated upon differentiation including the contact inhibition factor CDKN1C. Loss of GCM1 resulted in downregulation of CDKN1C and corresponding loss of contact inhibition, implicating GCM1 in regulation of this critical process.

Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor.

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation in circulating androgens during pregnancy, an independent risk factor linked to pregnancy complications and adverse outcomes in offspring. Yet, further studies are required to understand the effects of elevated androgens on cell type-specific placental dysfunction and fetal development. Therefore, a PCOS-like mouse model induced by continuous androgen exposure is examined. The PCOS-mice exhibited impaired placental and embryonic development, resulting in mid-gestation lethality. Co-treatment with the androgen receptor blocker, flutamide, prevents these phenotypes including germ cell specification. Comprehensive profiling of the placenta by whole-genome bisulfite and RNA sequencing shows a reduced proportion of trophoblast precursors, possibly due to the downregulation of Cdx2 expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated with reduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairs placental labyrinth formation. Importantly, human trophoblast organoids exposed to androgens exhibit analogous changes, showing impaired trophoblast differentiation as a key feature in PCOS-related pregnancy complications. These findings provide new insights into the potential cellular targets for future treatments.

Trends over time in the deficit of (instrumental) activities of daily living in the Austrian population aged 65 years and older : Results from the Austrian Health Interview Survey series.

BACKGROUND: Difficulties in activities of daily living (ADL) and instrumental activities of daily living (IADL) in older adults are associated with diminished quality of life and increased demand for long-term care. The present study examined the prevalence of disability among individuals aged 65 years and older in Austria, using data from the Austrian Health Interview Surveys (ATHIS). METHODS: The ATHIS 2014 and 2019 surveys were used (N = 5853) for the analysis. Binary logistic regression was performed to measure the association between disability in at least one ADL or IADL limitation and independent variables adjusted for sociodemographic, health-related behavior and survey year. RESULTS: The prevalence of ADL or IADL limitations increased in both sexes during the 5­year follow-up period. For ADL limitations, the prevalence rose from 12.8% to 17.9% in men (p < 0.001) and from 19.2% to 25.7% in women (p < 0.001). The IADL limitations increased from 18.9% to 35.1% in men (p < 0.001) and from 38.2% to 50.8% in women (p < 0.001). Women reported significantly higher odds for ADL (odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.93-1.26) and IADL limitations (OR: 1.74, 95% CI: 1.53-1.98). In both sexes, participants aged 80 years and older reported higher odds for ADL (OR: 4.37, 95% CI:3.77-5.07) and IADL limitations (OR: 4.43, 95% CI: 3.86-5.09) compared to the younger group. Participants with at least one chronic disease reported higher odds for ADL (OR: 4.00, 95% CI: 3.41-4.70) and IADL limitations (OR: 4.37, 95% CI: 3.85-4.96). Primary education, single status, being born in non-EU/EFTA countries, and residing in Vienna were associated with higher odds of ADL and IADL limitations. CONCLUSION: Gender, age, education, country of birth, residence, partnership status, number of chronic diseases, noncompliance with physical activity, and nutrition recommendations had a strong association with increased vulnerability to disability. Public health policy must address these factors for disability prevention strategies.

Step-by-step protocol for isolating the entire repertoire of human first trimester placental cells.

Correct placental development and function are essential for adapting the mother to the ongoing pregnancy and the wellbeing of the growing fetus; however, underlying processes are still poorly understood. Only limited structural and cellular placental features are shared among species hence requiring reliable human in-vitro models. Recently established trophoblast stem cell and organoid models significantly improved placental research; however, the human placenta constitutes a multi-cellular organ with tightly orchestrated, cellular and molecular networks between trophoblasts (TBs) and villous core cells (VCCs) vital for correct placentation. The establishment of co-culture models is accordingly the logical consequence to investigate TB and VCC interactions, but first requires efficient purification of ideally donor-matched placental cell types. We herein present a meticulously-tailored protocol based on four sequential digestion steps (d-steps) with varying enzyme compositions and digestion mode and length, gently releasing cells layer-by-layer from human first trimester placentae (8 - 9th week of gestation). Using immunofluorescence and flow cytometry, we analyzed the tissue fragments and digestion solutions after every d-step and collected data on individual digestion progress as well as cell viability, counts, and specifications. D-step 1 revealed a significantly low viability and was mainly composed of syncytial fragments, extravillous trophoblasts EVTs, and maternal leukocytes. D-step 2 and 3, comprising high viability predominantly contained TBs (90-99 %) with a significant enrichment of EVTs in d-step 2 and an almost pure villous cytotrophoblast (vCTB) population in d-step 3. D-step 4 finally enabled isolating fetal VCCs consisting of endothelial cells, fibroblasts, and Hofbauer cells. Interestingly, maternal leukocytes were detected in d-step 1 and 2 but completely absent from d-step 3 and 4 revealing pure fetal cell populations. In sum, we present a detailed guideline for stepwise isolating selected placental cell types suitable for further studies and co-culture models investigating TB and VCC interactions involved in early placental development.

Chronic exercise effects on overall depression severity and distinct depressive symptoms in older adults: A protocol of a systematic and meta-analytic review.

INTRODUCTION: There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics. METHODS: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis. CONCLUSION: The results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs. PROTOCOL REGISTRATION NUMBER: This protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418).

Perceptions of Therapeutic Climbing for Patients with Multiple Sclerosis in Neurorehabilitation: A Qualitative Study.

BACKGROUND: Therapeutic climbing (TC) has emerged as a prospective rehabilitation approach for individuals with multiple sclerosis (MS). The existing literature primarily focuses on the physical and psychological benefits of TC across diverse populations but is limited concerning its application and efficacy for patients with MS. OBJECTIVES: This study aimed to delineate the experiences, subjective effects, and perceptions of both individuals with MS and therapists regarding TC, highlighting the potential benefits and challenges of this therapeutic approach. METHODS: Using a qualitative design, semi-structured interviews were conducted with patients living with MS (N = 5) and therapists (N = 7) involved in TC sessions at a rehabilitation facility. The interviews were recorded, transcribed verbatim, and subjected to thematic qualitative text analysis. RESULTS: Our analysis resulted in the identification of five main categories: (1) motivational factors, (2) training conditions, (3) training content, (4) observed effects, and (5) safety protocol. Our findings primarily centred around the motivational aspects of TC. Participants consistently reported experiencing feelings of accomplishment, success, enjoyment, and increased self-confidence. Furthermore, TC was often perceived as a comprehensive intervention, addressing endurance, strength, flexibility, neuromotor functions, cognition, and mental health while having a low-risk profile. However, due to the demanding nature of TC, careful fatigue management is crucial. This entails personalised intensity adjustments during sessions and coordinating TC with other physically demanding therapies when implementing TC within a rehabilitation environment. CONCLUSIONS: TC shows promise within MS rehabilitation and can be considered safe under certain framework conditions. This research sheds light on its potential benefits, facilitators, and barriers and provides insights for practical integration into rehabilitation programs.

Experiences of Vegans with General Practitioners in the Austrian Health Care System: A Qualitative Study.

This article explores the factors influencing the choice of general practitioners (GPs) and their role in the health care of vegans in Austria. The number of people identifying as vegan is on the rise, and GPs are increasingly confronted with vegan patients. A qualitative method was chosen for this study, and 14 semi-structured interviews with vegans were conducted between April 2022 and July 2022. Participants were recruited primarily through vegan social media groups. In their experiences with health care, vegans felt treated unequally or sometimes incorrectly. The experiences described highlight that participants felt that most GPs were biased against their veganism. Information exchange among vegans primarily takes place online and through publications of vegan associations, while GPs play a minor role in information provision. As the number of vegans grows, an appreciative way of communicating between GPs and vegan patients ought to be promoted. Voluntary interdisciplinary nutritional training, collaboration of the medical field with support organizations, provision of evidence-based information, and collaboration with dietitians and nutritionists could enrich the care of patients with a vegan diet.

Cancer risk factors and access to cancer prevention services for people experiencing homelessness.

Cancer is one of the most pressing global health issues, and populations with complex needs, such as people experiencing homelessness, have higher cancer incidence and mortality rates compared with the housed population. We mapped the evidence on cancer risk factors as well as barriers and facilitators to cancer prevention services among people experiencing homelessness, which is key to localising research gaps and identifying strategies for tailored interventions adapted to people experiencing homelessness. The results of 40 studies contribute to an understanding of the dynamic, interactive factors at different levels that determine access to cancer prevention services: socioeconomic, psychological, and physical factors (individual level); practical support and relational loops between health-care providers and people experiencing homelessness (interpersonal level); housing and regular medical care (system level); and interventions to facilitate access to cancer prevention (policy level). Furthermore, studies reported higher prevalence of various cancer-associated risk factors among people experiencing homelessness with the most common being tobacco use, ranging from 26% to 73%. The results show the importance of interventions to facilitate cancer prevention services through social support and low-threshold interventions (eg, navigation programmes), and training health-care staff in creating supportive and trusting environments that increase the likelihood of the continuity of care among people experiencing homelessness.

Trophoblast Organoids as a Novel Tool to Study Human Placental Development and Function.

The human placenta provides the site of exchange between the maternal and fetal bloodstreams, acts as an endocrine organ, and has immunological functions. The majority of pregnancy disorders including preeclampsia and fetal growth restriction have their roots in pathological placentation. Yet, the underlying molecular causes of these complications remain largely unknown, not least due to the lack of reliable in vitro models. Recent establishment of 2D human trophoblast stem cells and 3D trophoblast organoids has been a major advancement that opened new avenues for trophoblast research. Here we provide a protocol detailing isolation of cytotrophoblast from the first trimester human placenta, establishment of trophoblast organoids, their culture and differentiation conditions. Overall, we describe an in vitro system that offers an excellent model to study the molecular basis of placental development and disease.

Gene-network based analysis of human placental trophoblast subtypes identifies critical genes as potential targets of therapeutic drugs.

During early pregnancy, extravillous trophoblasts (EVTs) play a crucial role in modifying the maternal uterine environment. Failures in EVT lineage formation and differentiation can lead to pregnancy complications such as preeclampsia, fetal growth restriction, and pregnancy loss. Despite recent advances, our knowledge on molecular and external factors that control and affect EVT development remains incomplete. Using trophoblast organoid in vitro models, we recently discovered that coordinated manipulation of the transforming growth factor beta (TGFß) signaling is essential for EVT development. To further investigate gene networks involved in EVT function and development, we performed weighted gene co-expression network analysis (WGCNA) on our RNA-Seq data. We identified 10 modules with a median module membership of over 0.8 and sizes ranging from 1005 (M1) to 72 (M27) network genes associated with TGFß activation status or in vitro culturing, the latter being indicative for yet undiscovered factors that shape the EVT phenotypes. Lastly, we hypothesized that certain therapeutic drugs might unintentionally interfere with placentation by affecting EVT-specific gene expression. We used the STRING database to map correlations and the Drug-Gene Interaction database to identify drug targets. Our comprehensive dataset of drug-gene interactions provides insights into potential risks associated with certain drugs in early gestation.

Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross-Sectional Study.

Background: The apolipoprotein E (APOE) ε4 allele has been associated with cognitive decline in Parkinson's disease (PD), but little is known about its relationship with motor and other nonmotor symptoms and whether APOE ε4 retains an influence on cognition when other factors are considered. Objective: To investigate the impact of APOE ε4 on motor/nonmotor symptoms and its relationship with other factors affecting cognition in individuals with PD. Methods: We analyzed data from 7616 individuals, comparing motor/nonmotor symptoms in different APOE genotypes using binary logistic regression. Multivariate logistic regression examined factors associated with cognitive impairments, including APOE ε4, Geriatric Depression Scale (GDS) score, Non-motor Symptom Questionnaire (NMS) score, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score, and physical activity level. Results: APOE ε4 heterozygosity was modestly associated with lower cognitive scores (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.87-0.99), whereas no significant association was found for any other nonmotor and motor symptoms. However, in multivariate analysis, cognitive impairment was associated with higher GDS (OR, 1.28; 95% CI, 1.23-1.34), NMS (OR, 1.22; 95% CI, 1.19-1.25), and MDS-UPDRS Part II (OR, 1.07; 95% CI, 1.06-1.09) scores, whereas physical activity was negatively associated (OR, 0.99; 95% CI, 0.98-0.99). APOE ε4 was no longer significant after adjusting for these factors. Conclusions: There is a link between cognition and APOE ε4 in patients with PD; however, when considering multiple factors, APOE ε4 plays a subordinate role. Other factors, such as depression, physical activity, and other nonmotor symptoms, demonstrate a stronger influence on cognitive impairment.

Health aspects of vegan diets among children and adolescents: a systematic review and meta-analyses.

Health effects of vegan diets among children and adolescents are a controversial public health topic. Thus, the aim of the present systematic review is to evaluate a broad range of health outcomes among vegan children and adolescents aged 0 to 18 years. 18 studies met the inclusion criteria (17 cross-sectional, 1 RCT). Meta-analyses showed lower protein, calcium, vitamin B2, saturated fatty acid, and cholesterol intakes, and lower ferritin, HDL and LDL levels as well as height in vegan compared to omnivorous children/adolescents. Higher intakes of carbohydrates, polyunsaturated fatty acids, fiber, folate, vitamins C and E, magnesium, iron, and potassium were observed in vegans. Blood levels of vitamin B12 were higher among vegan children due to supplement use. Single study results suggested further differences between vegan and non-vegan children, such as lower bone mineral content or urinary iodine among vegan children. Risk of Bias was rated as high or very high in 7 out of 18 studies. The certainty of evidence for the meta-analyses was low (n = 2) or very low (n = 46). Overall, the available evidence points to both risks and benefits associated with a vegan diet among children, although more and better designed studies are needed.

NOTCH3 signalling controls human trophoblast stem cell expansion and differentiation.

Failures in growth and differentiation of the early human placenta are associated with severe pregnancy disorders such as pre-eclampsia and fetal growth restriction. However, regulatory mechanisms controlling development of placental epithelial cells, the trophoblasts, remain poorly elucidated. Using trophoblast stem cells (TSCs), trophoblast organoids (TB-ORGs) and primary cytotrophoblasts (CTBs) of early pregnancy, we herein show that autocrine NOTCH3 signalling controls human placental expansion and differentiation. The NOTCH3 receptor was specifically expressed in proliferative CTB progenitors and its active form, the nuclear NOTCH3 intracellular domain (NOTCH3-ICD), interacted with the transcriptional co-activator mastermind-like 1 (MAML1). Doxycycline-inducible expression of dominant-negative MAML1 in TSC lines provoked cell fusion and upregulation of genes specific for multinucleated syncytiotrophoblasts, which are the differentiated hormone-producing cells of the placenta. However, progenitor expansion and markers of trophoblast stemness and proliferation were suppressed. Accordingly, inhibition of NOTCH3 signalling diminished growth of TB-ORGs, whereas overexpression of NOTCH3-ICD in primary CTBs and TSCs showed opposite effects. In conclusion, the data suggest that canonical NOTCH3 signalling plays a key role in human placental development by promoting self-renewal of CTB progenitors.

Cancer risk factors and access to cancer prevention services for people experiencing homelessness: a scoping review protocol.

INTRODUCTION: Homelessness is a complex social issue that significantly impairs the health of those affected. People experiencing homelessness (PEH) have a higher prevalence of adverse health outcomes, including premature mortality, compared with the general population, with cancer being the second-leading cause of death. The objective of this scoping review is to map the evidence to assess the exposure of PEH to known cancer risk factors and identify barriers and facilitators PEH experience in accessing cancer prevention services. METHODS AND ANALYSIS: This scoping review will be conducted in line with the Joanna Briggs Institute guidelines for scoping reviews. For a time window from the date of database establishment until 20 February 2023, the research team will create a detailed search strategy and apply it to the following databases: CINAHL, Embase, Global Index Medicus, PubMed, Scopus and Web of Science. In addition, we will search OpenGrey and Google for grey literature and contact non-governmental organisations to request relevant reports. In the first stage, eligibility criteria will be assessed through a blinded title/abstract assessment, and following this assessment, a full-text screening will be performed. Subsequently, the research team will perform the data extraction and synthesise all relevant information in relation to the scoping review question. ETHICS AND DISSEMINATION: As this protocol does not involve gathering primary data, ethical approval is not necessary. The results of this review will be published in a peer-reviewed journal and on institutional websites.

Generation of extracellular fluids from first-trimester decidual tissues and their validation by detecting tissue-specific secreted proteins.

The human placenta comes in direct contact with maternal cells and blood at two interfaces. The syncytiotrophoblast layer is surrounded by maternal blood at the intervillous space, and extravillous trophoblasts breach the vascular endothelial cells layer upon spiral artery remodeling and invasion of decidual veins. However, little knowledge exists about EVT-derived secreted factors, which may serve as predictive markers for obstetrical syndromes or shape the local environment at the maternal-fetal interface. Here, we define secreted EVT-associated genes and describe a method that yields interstitial fluids from patient-matched first-trimester decidua basalis and parietalis tissues.

The Association between Vegan Dietary Patterns and Physical Activity-A Cross-Sectional Online Survey.

A balanced diet and sufficient physical activity (PA) are known to have positive health effects. The relationship between a vegan diet and PA levels is understudied. This cross-sectional online survey aimed to analyze whether different vegan dietary patterns differ in PA. In total, 516 vegan participants were included (June to August 2022). Different dietary patterns were compiled through principal component analysis, while group differences were calculated using independent tests, or chi-squared tests as well as logistic regression analyses. The population had an average age of 28.0 (SD: 7.7) years and had been living vegan for 2.6 (95% CI: 2.5-3.0) years. Two dietary patterns, the "convenience" and the "health-conscious" group, were identified. People with a convenience dietary pattern had significantly higher odds of sitting more (OR 1.10, 95% CI 1.04-1.18) and not achieving aerobic PA (OR 1.81, 95% CI 1.18-2.79) or strength training recommendations (OR 1.81, 95% CI 1.26-2.61) than people with a health-conscious dietary pattern. This study suggests the heterogeneity of vegan diets and that dietary patterns must be differentiated, as they also differ in the level of PA. Additional studies involving complete dietary assessment with a focus on ultraprocessed foods, blood metabolite analysis, and objective PA assessment are required.

Human organoid systems in modeling reproductive tissue development, function, and disease.

Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to human embryonic material has necessitated the use of animals, primarily rats and mice, and short-term primary cell cultures derived from human patient material. While reproductive developmental processes are generally conserved across mammals, specific features unique to human reproduction have resulted in the development of human-based in vitro systems designed to retain or recapitulate key molecular and cellular processes important in humans. Of note, major advances in 3D epithelial stem cell-based systems modeling human reproductive organ development have been made. These cultures, broadly referred to as organoids, enable research aimed at understanding cellular hierarchies and processes controlling cellular differentiation and function. Moreover, organoids allow the pre-clinical testing of pharmacological substances, both from safety and efficacy standpoints, and hold large potential in driving aspects of personalized medicine that were previously not possible with traditional models. In this mini-review, we focus on summarizing the current state of regenerative organoid culture systems of the female and male reproductive tracts that model organ development, maintenance, and function. Specifically, we will introduce stem cell-based organoid models of the ovary/fallopian tube, endometrium, cervix, prostate gland, and testes. We will also describe organoid systems of the pre-implanting blastocyst and trophoblast, as the blastocyst and its extraembryonic trophectoderm are central to fetal, maternal, and overall pregnancy health. We describe the foundational studies leading to their development and outline the utility as well as specific limitations that are unique and common to many of these in vitro platforms.

The human placenta shapes the phenotype of decidual macrophages.

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.