Placental Origins of Chronic Disease

Physiological Reviews, Год журнала: 2016, Номер 96(4), С. 1509 - 1565

Опубликована: Сен. 8, 2016

Epidemiological evidence links an individual's susceptibility to chronic disease in adult life events during their intrauterine phase of development. Biologically this should not be unexpected, for organ systems are at most plastic when progenitor cells proliferating and differentiating. Influences operating time can permanently affect structure functional capacity, the activity enzyme endocrine axes. It is now appreciated that such effects lay foundations a diverse array diseases become manifest many years later, often response secondary environmental stressors. Fetal development underpinned by placenta, forms interface between fetus its mother. All nutrients oxygen reaching must pass through organ. The placenta also has major functions, orchestrating maternal adaptations pregnancy mobilizing resources fetal use. In addition, it acts as selective barrier, creating protective milieu minimizing exposure hormones, glucocorticoids, xenobiotics, pathogens, parasites. shows remarkable capacity adapt adverse cues lessen impact on fetus. However, if placental function impaired, or exceeded, then may compromised. Here, we explore complex relationships phenotype developmental programming offspring. Ensuring optimal placentation offers new approach prevention disorders cardiovascular disease, diabetes, obesity, which epidemic proportions.

Язык: Английский

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Human placenta and trophoblast development: key molecular mechanisms and model systems

Cellular and Molecular Life Sciences, Год журнала: 2019, Номер 76(18), С. 3479 - 3496

Опубликована: Май 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.

Язык: Английский

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Sex as a Biological Variable: A 5-Year Progress Report and Call to Action

Journal of Women s Health, Год журнала: 2020, Номер 29(6), С. 858 - 864

Опубликована: Янв. 23, 2020

A little over 5 years ago, the U.S. National Institutes of Health (NIH) announced intention to develop policies require applicants report plans balance male and female cells animals in preclinical investigations. Soon thereafter, NIH issued a request for information from scientific community consulted with various stakeholders. The feedback received was considered during development policy requiring consideration sex as biological variable (SABV) NIH-funded research on vertebrate humans, which went into effect applications due or after January 25, 2016. We identified programs related SABV reviewed SABV-relevant literature. find that application throughout process can serve guiding principle improve value biomedical science. is engaged ongoing efforts resources help investigators consider their research. also provide an update lessons learned, highlight ways different disciplines SABV, describe opportunities discovery applying offers. call NIH's stakeholders redouble integrate enterprise. Sex- gender-aware investigations are critical conduct rigorous transparent science advancement personalized medicine. This kind achieves its greatest potential when gender considerations integrated enterprise end-to-end manner, basic investigations, through translational clinical research, improved health care delivery.

Язык: Английский

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Convergence of placenta biology and genetic risk for schizophrenia

Nature Medicine, Год журнала: 2018, Номер 24(6), С. 792 - 801

Опубликована: Май 24, 2018

Язык: Английский

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Sex differences in the gut microbiome–brain axis across the lifespan

Philosophical Transactions of the Royal Society B Biological Sciences, Год журнала: 2016, Номер 371(1688), С. 20150122 - 20150122

Опубликована: Фев. 1, 2016

In recent years, the bidirectional communication between gut microbiome and brain has emerged as a factor that influences immunity, metabolism, neurodevelopment behaviour. Cross-talk begins early in life immediately following transition from sterile utero environment to one is exposed changing complex microbial milieu over lifetime. Once established, integrates information autonomic enteric nervous systems, neuroendocrine neuroimmune signals, peripheral immune metabolic signals. Importantly, composition functional potential of undergoes many transitions parallel dynamic periods development maturation for which distinct sex differences have been identified. Here, we discuss sexually dimorphic development, maintenance microbiome–brain axis, therein important disease risk resilience throughout lifespan.

Язык: Английский

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A Review of Systemic Corticosteroid Use in Pregnancy and the Risk of Select Pregnancy and Birth Outcomes

Rheumatic Disease Clinics of North America, Год журнала: 2017, Номер 43(3), С. 489 - 502

Опубликована: Июль 13, 2017

Язык: Английский

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What is resilience: an affiliative neuroscience approach

World Psychiatry, Год журнала: 2020, Номер 19(2), С. 132 - 150

Опубликована: Май 11, 2020

Resilience - a key topic in clinical science and practice still lacks clear conceptualization that integrates its evolutionary human-specific features, refrains from exclusive focus on fear physiology, incorporates developmental approach, and, most importantly, is not based the negation (i.e., absence of symptoms following trauma). Building initial condition mammals, whose brain matures context mother's body caregiving behavior, we argue systems processes participate tuning to social ecology adapting hardships mark construct resilience. These include oxytocin system, affiliative brain, biobehavioral synchrony, all characterized by great flexibility across phylogenesis ontogenesis. Three core features resilience are outlined: plasticity, sociality meaning. Mechanisms which coordinated action supports diversity, endurance adaptation described animal evolution. Humans' synchrony maternal attuned behavior postpartum adult-adult relationships empathy, perspective-taking intimacy, extends mother-child relationship other bonds throughout life, charting fundamental trajectory development Findings three high-risk cohorts, each tapping distinct disruption maternal-infant bonding (prematurity, depression, early life stress/trauma), followed birth adolescence/young adulthood, demonstrate how components neurobiology affiliation confer uniquely shape brain.

Язык: Английский

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Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes

Proceedings of the National Academy of Sciences, Год журнала: 2019, Номер 116(48), С. 23996 - 24005

Опубликована: Окт. 14, 2019

Significance Despite decades of prenatal programming research showing that “the womb may be more important than the home” with respect to offspring health outcomes, no studies which we are aware have considered multiple indicators maternal stress identify types most influence developing offspring. This study’s key contributions include use a data-driven procedure specify stress—psychological and subclinical physical indicators—that predict outcomes including sex at birth, risk preterm fetal neurodevelopment. Social support is factor differentiating groups malleable intervention target improve outcomes.

Язык: Английский

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The complex aetiology of cerebral palsy

Nature Reviews Neurology, Год журнала: 2018, Номер 14(9), С. 528 - 543

Опубликована: Авг. 13, 2018

Язык: Английский

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The placenta and neurodevelopment: sex differences in prenatal vulnerability

Dialogues in Clinical Neuroscience, Год журнала: 2016, Номер 18(4), С. 459 - 464

Опубликована: Дек. 31, 2016

Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including rates of autism, mental retardation, stuttering, dyslexia, attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin sex chromosomes, likely to produce sex-specific transplacental signals developing brain. Our studies others have identified X-linked genes that expressed at higher levels female placenta. Through a genome-wide screen after stress mice, we gene O-linked N-acetylglucosamine transferase (OGT) demonstrated its causality programming producing male-specific phenotype. Elucidating molecular mechanisms involved brain development is key understanding bias disorders expected yield novel insight into resilience.Las agresiones prenatales, como el estrés materno, están asociadas con un aumento del riesgo de enfermedades neurodesarrollo y impacto en los hombres es significativamente mayor que las mujeres, incluyendo frecuencias autismo, retardo mental, tartamudez, dislexia trastorno por déficit atención e hiperactividad (TDAH). Las diferencias sexo la parten ya cromosomas sexuales, probable produzcan señales transplacentarias sexo-específicas para cerebro desarrollo. Los estudios nuestros otros han identificado ligados al cromosoma X tienen una expresión placenta hembras. Mediante evaluación ratones genoma completo después identificamos gen transferasa N-acetilglucosamina O unida (OGT), ligado demostramos su causalidad programación da origen fenotipo específico machos. La clarificación mecanismos moleculares sexo-específicos involucrados afectan desarrollo cerebral clave comprender sesgo trastornos se espera conduzcan nueva visión acerca riesgos resiliencia enfermedades.Les atteintes prénatales, comme le maternel, sont associées à risque accru maladies neurodéveloppementales et affectent significativement davantage les garçons filles, avec une augmentation des taux d'autisme, retard bégaiement, dyslexie troubles du l'attention ou sans hyperactivité Les différences sexe au niveau qui commencent chromosomes sexuels, semblent transmettre signaux transplacentaires spécifiques cerveau développement. Nos études, d'autres, ont identifié gènes liés l'X, exprimés niveaux plus élevés dans filles. Après maternel chez souris, nous avons identifié, grâce analyse systématique génome, gène N-acétylglucosamine transférase est lié démontré sa causalité programmation neurodéveloppementale produisant phénotype spécifique l'homme. L'élucidation mécanismes moléculaires impliqués impactent développement cérébral clé compréhension biais neurodéveloppementaux améliorera notre connaissance risques résilience maladies.

Язык: Английский

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