Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene DOI Creative Commons
Jorge López‐Tello, Hannah E. J. Yong, Ionel Sandovici

et al.

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1195 - 1208.e6

Published: July 1, 2023

Maternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology enhance placental nutrient transfer, but the mechanisms involved remain unclear. imprinted Igf2 gene is highly expressed murine endocrine cells. Here, we show that deletion these cells impairs signaling mother, without affecting morphology. controls hormone production, including prolactins, crucial establish pregnancy-related insulin resistance partition nutrients fetus. Consequently, fetuses lacking are growth restricted hypoglycemic. Mechanistically, protein synthesis cellular energy homeostasis, actions dependent on cell type. loss also additional long-lasting effects offspring metabolism adulthood. Our study provides compelling evidence for an intrinsic fetal manipulation system operating placenta modifies resource allocation, with long-term consequences metabolic health.

Language: Английский

Human placenta and trophoblast development: key molecular mechanisms and model systems DOI Creative Commons
Martin Knöfler, Sandra Haider, Leila Saleh

et al.

Cellular and Molecular Life Sciences, Journal Year: 2019, Volume and Issue: 76(18), P. 3479 - 3496

Published: May 3, 2019

Abnormal placentation is considered as an underlying cause of various pregnancy complications such miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing risk for development severe disorders in later life cardiovascular disease type 2 diabetes. Despite their importance, molecular mechanisms governing human placental formation trophoblast cell lineage specification differentiation have been poorly unravelled, mostly due to lack appropriate cellular model systems. However, over past few years major progress has made by establishing self-renewing stem cells 3-dimensional organoids from blastocysts early tissues opening path detailed investigations. Herein, we summarize present knowledge about development, its cells, progenitors differentiated types epithelium villous core. Anatomy placenta, current systems, critical key regulatory factors signalling cascades will be elucidated. In this context, discuss role developmental pathways Wingless Notch, controlling stemness/differentiation invasive progenitors, respectively.

Language: Английский

Citations

610

Mechanisms of early placental development in mouse and humans DOI
Myriam Hemberger, Courtney W. Hanna, Wendy Dean

et al.

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 21(1), P. 27 - 43

Published: Sept. 18, 2019

Language: Английский

Citations

380

Developmental origins of metabolic diseases DOI
Daniël J. Hoffman, Theresa L. Powell, Emily S. Barrett

et al.

Physiological Reviews, Journal Year: 2020, Volume and Issue: 101(3), P. 739 - 795

Published: Dec. 3, 2020

Almost 2 billion adults in the world are overweight, and more than half of them classified as obese, while nearly one-third children globally experience poor growth development. Given vast amount knowledge that has been gleaned from decades research on development, a number questions remain to why is now midst global epidemic obesity accompanied by "double burden malnutrition," where overweight coexists with underweight micronutrient deficiencies. This challenge human condition can be attributed nutritional environmental exposures during pregnancy may program fetus have higher risk chronic diseases adulthood. To explore this concept, frequently called developmental origins health disease (DOHaD), review considers host factors physiological mechanisms drive or child toward obesity, fatty liver disease, hypertension, and/or type diabetes (T2D). end, explores epidemiology DOHaD discussions focused adaptations energetics, placental dysmetabolism, key act promote These areas complementary additive understanding how providing best conditions for optimal create possible lifelong health. Moreover, both well epigenetic molecular vital most fully address issues other diseases.

Language: Английский

Citations

275

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery DOI Creative Commons

Rebekah Omarkhail Elliott,

Mei He

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(1), P. 122 - 122

Published: Jan. 19, 2021

Since the 2013 Nobel Prize was awarded for discovery of vesicle trafficking, a subgroup nanovesicles called exosomes has been driving research field to new regime understanding cellular communication. This exosome-dominated traffic control system increased many diseases, including cancer metastasis, diabetes, and HIV. In addition important diagnostic role, are particularly attractive drug delivery, due their distinctive properties in information transfer uptake. Compared viral non-viral synthetic systems, natural, cell-derived exhibit intrinsic payload bioavailability. Most importantly, easily cross biological barriers, obstacles that continue challenge other delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles blood–brain barrier (BBB), blood–cerebrospinal fluid (BCSFB), blood–lymph (BlyB), blood–air (BAB), stromal (SB), blood–labyrinth (BLaB), blood–retinal (BRB), placental (PB), which opens exciting possibilities using as platform. However, systematic reviews summarizing such discoveries still limited. review covers state-of-the-art exosome on crossing several barriers with focus current, accepted models used explain mechanisms crossing, tight junctions. The potential design engineer enhance efficacy, leading future applications precision medicine immunotherapy, is discussed.

Language: Английский

Citations

185

The transition to motherhood: linking hormones, brain and behaviour DOI
Camila Servin-Barthet, Magdalena Martínez‐García, Clara Pretus

et al.

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(10), P. 605 - 619

Published: Aug. 23, 2023

Language: Английский

Citations

57

Interdisciplinary fetal-neonatal neurology training applies neural exposome perspectives to neurology principles and practice DOI Creative Commons
Mark S. Scher

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

An interdisciplinary fetal-neonatal neurology (FNN) program over the first 1,000 days teaches perspectives of neural exposome that are applicable across life span. This curriculum strengthens neonatal neurocritical care, pediatric, and adult training objectives. Teaching at maternal-pediatric hospital centers optimally merges reproductive, pregnancy, pediatric approaches to healthcare. Phenotype–genotype expressions health or disease pathways represent a dynamic developmental time. The science uncertainty applied FNN re-enforces importance shared clinical decisions minimize bias reduce cognitive errors. Trainees select mentoring committee participants will maximize their learning experiences. Standardized questions oral presentations monitor educational progress. Master doctoral defense preparation competitive research funding can be goals for specific individuals. principles practice offer an understanding gene–environment interactions recognizes effects reproductive on maternal-placental-fetal triad, neonate, child, adult. Pre-conception prenatal adversities potentially diminish life-course brain health. Endogenous exogenous toxic stressor interplay (TSI) alters through maladaptive neuroplasticity. Developmental disorders epilepsy primarily expressed during days. Communicable noncommunicable illnesses continue interact with express diverse neurologic lifespan, particularly critical/sensitive time periods adolescence senescence. Anomalous destructive fetal neuropathologic lesions change this developmental-aging continuum. integrated placental, neonatal, childhood, offers perspective exposome. Exosome promises improved monitoring drug delivery starting pregnancy. origins anticipate diagnoses interventions benefit successive generations. Addressing care disparities in Global South high-income country medical deserts require constructive dialogue among stakeholders achieve equity. Population policies capital strategy reduces global burden diseases by applying practice. integrative approach prolong survival quality persons lifespan confronted neurological disorders.

Language: Английский

Citations

21

Placenta: an old organ with new functions DOI Creative Commons

Sara Khorami-Sarvestani,

Negar Vanaki,

Sorour Shojaeian

et al.

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

Citations

19

Pregnancy entails a U-shaped trajectory in human brain structure linked to hormones and maternal attachment DOI Creative Commons
Camila Servin-Barthet, Magdalena Martínez‐García, María Paternina-Die

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 16, 2025

Growing evidence places the gestational period as a unique moment of heightened neuroplasticity in adult life. In this longitudinal study spanning pre, during, and post pregnancy, we unveil U-shaped trajectory gray matter (GM) volume, which dips late pregnancy partially recovers during postpartum. These changes are most prominent brain regions associated with Default Mode Frontoparietal Network. The is predominantly linked to factors, it only presents mothers correlates fluctuations estrogens over time. Finally, mother's mental health status mediates relationship between postpartum GM volume recovery maternal attachment at 6 months This research sheds light on complex interplay hormones, development, behavior transition motherhood. It addresses significant knowledge gap neuroscience human opens new possibilities for interventions aimed enhancing well-being.

Language: Английский

Citations

2

Pivotal role of the transcriptional co-activator YAP in trophoblast stemness of the developing human placenta DOI Creative Commons
Gudrun Meinhardt, Sandra Haider, Victoria Kunihs

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(24), P. 13562 - 13570

Published: June 1, 2020

Various pregnancy complications, such as severe forms of preeclampsia or intrauterine growth restriction, are thought to arise from failures in the differentiation human placental trophoblasts. Progenitors latter either develop into invasive extravillous trophoblasts, remodeling uterine vasculature, fuse multinuclear syncytiotrophoblasts transporting oxygen and nutrients growing fetus. However, key regulatory factors controlling trophoblast self-renewal have been poorly elucidated. Using primary cells, three-dimensional organoids, CRISPR-Cas9 genome-edited JEG-3 clones, we herein show that YAP, transcriptional coactivator Hippo signaling pathway, promotes maintenance cytotrophoblast progenitors by different genomic mechanisms. Genetic chemical manipulation YAP these cellular models revealed it stimulates proliferation expression cell cycle regulators stemness-associated genes, but inhibits fusion production syncytiotrophoblast (STB)-specific proteins, hCG GDF15. Genome-wide comparisons villous cytotrophoblasts overexpressing constitutively active YAP-5SA with KO cells syncytializing trophoblasts common target genes involved stemness differentiation. ChIP-qPCR unraveled overexpression increased binding YAP–TEAD4 complexes promoters proliferation-associated CCNA CDK6 . Moreover, repressive containing histone methyltransferase EZH2 were detected regions STB-specific CGB5 CGB7 genes. In summary, plays a pivotal role epithelium. Besides activating factors, also directly represses promoting fusion.

Language: Английский

Citations

127

Energy Intake Requirements in Pregnancy DOI Open Access
Jasper Most, Sheila Dervis, François Haman

et al.

Nutrients, Journal Year: 2019, Volume and Issue: 11(8), P. 1812 - 1812

Published: Aug. 6, 2019

Energy intake requirements in pregnancy match the demands of resting metabolism, physical activity, and tissue growth. balance is, therefore, defined as energy equal to expenditure plus storage. A detailed understanding these components their changes throughout gestation can inform recommendations for minimizing risk poor outcomes. is sum activity-related expenditure. Resting metabolic rate increases during a result increased body mass, pregnancy-associated physiological changes, i.e., cardiac output, growing fetus. Physical activity extremely variable between women may change over course pregnancy. The requirement storage depends on maternal pregravid size. For optimal outcomes, with low weight require more fat mass accumulation than obesity, who do not accumulate at all. Given high density differences affect healthy greatly. In contrast, stored fetal placental tissues comparable all have small impact requirements. Different prediction equations been developed quantify we provide brief review strengths weaknesses discuss application management gain pregnant women.

Language: Английский

Citations

125