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1.
PLoS One ; 15(9): e0238225, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915841

RESUMO

Positional information on the shoulder girdle (the clavicle and scapula) is important for a better understanding of the function of the upper limb in the locomotive system as well as its associated disease pathogenesis. However, such data are limited except for information on the axial position of the scapula. Here, we describe a three-dimensional reconstruction of the shoulder girdle including the clavicle and scapula, and its relationship to different landmarks in the body. Thirty-six human fetal specimens (crown-rump length range: 7.6-225 mm) from the Kyoto Collection were used for this study. The morphogenesis and three-dimensional position of the shoulder girdle were analyzed with phase-contrast X-ray computed tomography and magnetic resonance imaging. We first detected the scapula body along with the coracoid and humeral head at Carnegie stage 18; however, the connection between the body and coracoid was not confirmed at this stage. During development, all landmarks on the shoulder girdle remained at the same axial position except for the inferior angle, which implies that the scapula enlarged in the caudal direction and reached the adult axial position in the fetal period. The scapula body was rotated internally and in the upward direction at the initiation of morphogenesis, but in the fetal period the scapula body was different than that in the adult position. The shoulder girdle was located at the ventral side of the vertebrae at the time of initial morphogenesis, but changed its position to the lateral side of the vertebrae in the late embryonic and fetal periods. Such a unique position of the shoulder girdle may contribute to the stage-specific posture of the upper limb. Adequate internal and upward rotation of the scapula could help in reducing the shoulder width, thereby facilitating childbirth. The data presented in this study can be used as normal morphometric references for shoulder girdle evaluations in the embryonic and fetal periods.


Assuntos
Desenvolvimento Fetal/fisiologia , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/anatomia & histologia , Articulação do Ombro/fisiologia , Ombro/embriologia , Ombro/fisiologia , Crescimento e Desenvolvimento , Humanos , Ombro/anatomia & histologia , Extremidade Superior/anatomia & histologia , Extremidade Superior/fisiologia
2.
PLoS One ; 15(8): e0236968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745140

RESUMO

Many circumstantial evidences from human and animal studies suggest that complement cascade dysregulation may play an important role in pregnancy associated complications including preeclampsia. Deletion of rodent specific complement inhibitor gene, Complement Receptor 1-related Gene/Protein y (Crry) produces embryonic lethal phenotype due to complement activation. It is not clear if decreased expression of Crry during pregnancy produces hypertensive phenotype. We downregulated Crry in placenta by injecting inducible lentivialshRNA vectors into uterine horn of pregnant C57BL/6 mice at the time of blastocyst hatching. Placenta specific downregulation of Crry without significant loss of embryos was achieved upon induction of shRNA using an optimal doxycycline dose at mid gestation. Crry downregulation resulted in placental complement deposition. Late-gestation measurements showed that fetal weights were reduced and blood pressure increased in pregnant mice upon downregulation of Crry suggesting a critical role for Crry in fetal growth and blood pressure regulation.


Assuntos
Desenvolvimento Fetal/fisiologia , Placenta/metabolismo , Receptores de Complemento 3b/genética , Animais , Pressão Sanguínea/genética , Ativação do Complemento/genética , Complemento C3/metabolismo , Inativadores do Complemento/farmacologia , Feminino , Desenvolvimento Fetal/genética , Regulação da Expressão Gênica/genética , Camundongos , Camundongos Endogâmicos C57BL , Placenta/fisiologia , Pré-Eclâmpsia/genética , Gravidez , RNA Interferente Pequeno/genética , Receptores de Complemento/genética , Receptores de Complemento 3b/metabolismo
4.
J Psychiatr Res ; 128: 1-4, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474140

RESUMO

Prenatal COVID-19 infection is anticipated by the U.S. Centers for Disease Control to affect fetal development similarly to other common respiratory coronaviruses through effects of the maternal inflammatory response on the fetus and placenta. Plasma choline levels were measured at 16 weeks gestation in 43 mothers who had contracted common respiratory viruses during the first 6-16 weeks of pregnancy and 53 mothers who had not. When their infants reached 3 months of age, mothers completed the Infant Behavior Questionnaire-Revised (IBQ-R), which assesses their infants' level of activity (Surgency), their fearfulness and sadness (Negativity), and their ability to maintain attention and bond to their parents and caretakers (Regulation). Infants of mothers who had contracted a moderately severe respiratory virus infection and had higher gestational choline serum levels (≥7.5 mM consistent with U.S. Food and Drug Administration dietary recommendations) had significantly increased development of their ability to maintain attention and to bond with their parents (Regulation), compared to infants whose mothers had contracted an infection but had lower choline levels (<7.5 mM). For infants of mothers with choline levels ≥7.5 µM, there was no effect of viral infection on infant IBQ-R Regulation, compared to infants of mothers who were not infected. Higher choline levels obtained through diet or supplements may protect fetal development and support infant early behavioral development even if the mother contracts a viral infection in early gestation when the brain is first being formed.


Assuntos
Betacoronavirus/patogenicidade , Encéfalo , Desenvolvimento Infantil , Colina , Desenvolvimento Fetal , Comportamento do Lactente , Complicações Infecciosas na Gravidez , Adulto , Atenção , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Colina/administração & dosagem , Colina/sangue , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Suplementos Nutricionais , Feminino , Desenvolvimento Fetal/efeitos dos fármacos , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Humanos , Lactente , Comportamento do Lactente/fisiologia , Comportamento do Lactente/psicologia , Masculino , Nootrópicos/administração & dosagem , Nootrópicos/sangue , Apego ao Objeto , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/virologia , Cuidado Pré-Natal/métodos
5.
Arch Gynecol Obstet ; 302(4): 837-844, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32583209

RESUMO

PURPOSE: Diabetes alters maternal metabolism and can lead to aberrant fetal growth. In addition to insulin treatment, nutritional diet interventions are recommended for promoting fetal health against diabetes-induced adverse effects. Therefore, we conducted an in vivo study to investigate betaine efficacy on fetal development against maternal diabetes. METHODS: Thirty-two dams were divided into four equal groups: control (C), betaine supplementation (BS), diabetic pregnancy (DP) and diabetic pregnancy plus betaine supplementation (DP + BS). Fasting blood sugar (FBS) and body weight (BW) were monitored during pregnancy. After physiological delivery, dams glycated hemoglobin (HbA1c) concentrations were measured, followed by fetal development indices including litter size (LS), neonatal weight (NW) and crown-rump (CR). Also, maternal oxidative status was assessed by evaluating glutathione (GSH) content, glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and malondialdehyde (MDA) concentration in the erythrocytes. RESULTS: Betaine supplementation significantly alleviated FBS and tended to recover BW loss. It also significantly decreased HbA1c values in dams of DP + BS compared to DP group. Normalized fetal indices such as LS, NW and CR under betaine supplementation were associated with a significant increase in GSH content and GSH-Px activity, as well as decreased MDA concentrations in erythrocytes of dams in the DP + BS versus the DP group, indicating improved redox balance in the dams. CONCLUSION: We indicated for the first time that betaine supplementation improved the maternal glucose metabolism and redox balance associated with normalized fetal growth. Nevertheless, further studies are required to investigate the mechanisms through which betaine protects fetal growth in diabetic pregnancy.


Assuntos
Betaína/administração & dosagem , Desenvolvimento Fetal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Gravidez em Diabéticas , Animais , Betaína/metabolismo , Peso Corporal/fisiologia , Suplementos Nutricionais , Feminino , Desenvolvimento Fetal/fisiologia , Retardo do Crescimento Fetal , Fármacos Gastrointestinais , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hemoglobina A Glicada/metabolismo , Malondialdeído/metabolismo , Gravidez , Substâncias Protetoras , Ratos
6.
Am J Obstet Gynecol ; 223(3): 312-321, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32565236

RESUMO

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide.


Assuntos
Promoção da Saúde/tendências , Resultado da Gravidez , Economia , Feminino , Desenvolvimento Fetal/genética , Desenvolvimento Fetal/fisiologia , Humanos , Assistência Perinatal , Gravidez , Complicações na Gravidez/etnologia , Complicações na Gravidez/genética , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologia , Resultado da Gravidez/genética , Psicologia
7.
PLoS One ; 15(6): e0235113, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574213

RESUMO

OBJECTIVES: Timely delivery of fetal growth restriction (FGR) is important in reducing stillbirth. However, targeted earlier delivery of FGR preferentially removes smaller babies from later gestations, thereby right-shifting the distribution of birthweights at term. This artificially increases the birthweight cutoffs defining the lower centiles and redefines normally grown babies as small by population-based birthweight centiles. Our objective was to compare updated Australian national population-based birthweight centile charts over time with the prescriptive INTERGROWTH-21st standard. METHODS: A retrospective descriptive study of all singleton births ≥34 weeks' gestation in Victoria, Australia in five two-year epochs: 1983-84, 1993-94, 2003-04, 2013-14, and 2016-17. The birthweight cutoffs defining the 3rd and 10th centile from three Australian national population-based birthweight centile charts, for births in 1991-1994, in 1998-2007, and 2004-2013 respectively, were applied to each epoch to calculate the proportion of babies with birthweight <3rd and <10th centile. The same analysis was done using the INTERGROWTH-21st birthweight standard. To assess change over gestation, proportions were also calculated at preterm, early term and late term gestations. RESULTS: From 1983-84 to 2016-17, the proportion of babies with birthweight <3rd fell across all birthweight centile charts, from 3.1% to 1.7% using the oldest Australian chart, from 3.9% to 1.9% using the second oldest Australian chart, from 4.3% to 2.2% using the most recent Australian chart, and from 2.0% to 0.9% using the INTERGROWTH-21st standard. A similar effect was evident for the <10th centile. The effect was most obvious at term gestations. Updating the Australian population birthweight chart progressively right-shifted the birthweight distribution, changing the definition of small over time. The birthweight distribution of INTERGROWTH-21st was left-shifted compared to the Australian charts. CONCLUSIONS: Locally-derived population-based birthweight centiles are better for clinical audit of care but should not be updated. Prescriptive birthweight standards are less useful in defining 'small' due to their significant left-shift.


Assuntos
Peso ao Nascer/fisiologia , Retardo do Crescimento Fetal/epidemiologia , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Natimorto/epidemiologia , Feminino , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Masculino , Vigilância da População/métodos , Gravidez , Estudos Retrospectivos , Vitória/epidemiologia
8.
Mol Immunol ; 123: 1-6, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380279

RESUMO

The repertoire of dendritic cells (DCs), monocytes and macrophages in adult humans is diverse and we are appreciating this to a greater extent as high throughput methods, such a single-cell RNA sequencing, become widely adopted and scalable. This powerful lens of analysis is also beginning to shed light on prenatal immunology, allowing us to chart the emergence, tissue distribution and developmental regulation of DCs, monocytes and macrophages during early human life. In this review, we will integrate recent insights from studies of the developing immune system into our understanding of adult DC, monocyte and macrophage organization, illustrating where insights from early life both affirm and challenge current understanding.


Assuntos
Células Dendríticas/citologia , Desenvolvimento Fetal/fisiologia , Macrófagos/citologia , Monócitos/citologia , Mielopoese/fisiologia , Análise de Célula Única/métodos , Adulto , Animais , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células Cultivadas , Células Dendríticas/fisiologia , Feminino , Humanos , Macrófagos/fisiologia , Monócitos/fisiologia , Gravidez
9.
Arch Gynecol Obstet ; 302(1): 65-75, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32409928

RESUMO

PURPOSE: Prenatal sub-optimal nutrition and exposure to maternal stress, anxiety and depression in pregnancy have been linked to increased postnatal morbidity and mortality. Fetal growth is most vulnerable to maternal dietary deficiencies, such as those evident in hyperemesis gravidarum (HG), early in pregnancy. The purpose of this pilot study was to examine the effects of HG on fetal movement profiles as a measure of fetal healthy development in the 3rd trimester of pregnancy, and to assess whether nutritional stress on the mother can be evaluated using isotopic analysis of hair. METHOD: We analyzed fetal movement profiles using 4D ultrasound scans at 32- and 36-weeks' gestation. Fetuses of women (N = 6) diagnosed with HG, having lost more than 10% of their body weight in the first trimester of pregnancy were compared to a healthy group (N = 6), controlling for stress, depression and anxiety. We tested carbon and nitrogen isotope ratios in maternal hair as a measure of both diet and nutritional changes due to catabolism of body proteins and fats. RESULTS: HG and catabolism were significantly correlated (p = 0.02). Furthermore, at 32-weeks' gestation movement profiles of fetuses of mothers with HG differed significantly from the movement profiles of fetuses of healthy mothers. Fetuses of mothers suffering from HG showed a significantly increased ratio of fine-grained movements at 32 weeks (p = 0.008); however, there were no significant differences detectable at 36-weeks' gestation. CONCLUSION: The effect of HG on fetal development as expressed by variations in fetal movement profiles in this pilot study suggest that prenatal effects of HG can be measured using movement profiles. Isotope analysis of hair can supplement this with information on nutritional imbalances early in pregnancy.


Assuntos
Desenvolvimento Fetal/fisiologia , Retardo do Crescimento Fetal , Movimento Fetal/fisiologia , Hiperêmese Gravídica/complicações , Saúde Mental/estatística & dados numéricos , Mães/psicologia , Estresse Psicológico , Adulto , Ansiedade , Dieta , Feminino , Tomografia Computadorizada Quadridimensional , Idade Gestacional , Humanos , Hiperêmese Gravídica/epidemiologia , Projetos Piloto , Gravidez , Terceiro Trimestre da Gravidez
10.
Sci China Life Sci ; 63(6): 849-865, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32291558

RESUMO

The number of growth factors involved in female fertility has been extensively studied, but reluctance to add essential growth factors in culture media has limited progress in optimizing embryonic growth and implantation outcomes, a situation that has ultimately led to reduced pregnancy outcomes. Insulin-like growth factor II (IGF-II) is the most intricately regulated of all known reproduction-related growth factors characterized to date, and is perhaps the predominant growth factor in human ovarian follicles. This review aims to concisely summarize what is known about the role of IGF-II in follicular development, oocyte maturation, embryonic development, implantation success, placentation, fetal growth, and in reducing placental cell apoptosis, as well as present strategies that use growth factors in culture systems to improve the developmental potential of oocytes and embryos in different species. Synthesizing the present knowledge about the physiological roles of IGF-II in follicular development, oocyte maturation, and early embryonic development should, on the one hand, deepen our overall understanding of the potential beneficial effects of growth factors in female reproduction and on the other hand support development (optimization) of improved outcomes for assisted reproductive technologies.


Assuntos
Fator de Crescimento Insulin-Like II/genética , Fator de Crescimento Insulin-Like II/fisiologia , Reprodução/fisiologia , Animais , Desenvolvimento Embrionário/fisiologia , Feminino , Desenvolvimento Fetal/fisiologia , Regulação da Expressão Gênica , Humanos , Oócitos/fisiologia , Folículo Ovariano/fisiologia , Gravidez
11.
Int J Pediatr Otorhinolaryngol ; 133: 109973, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32163824

RESUMO

OBJECTIVES: The auricle is a key target in pediatric plastic surgery and is considered to develop from a ring- or funnel-like arrangement of six hillocks in the embryo. However, there has been no report showing the morphologies of the auricular muscle and cartilage after midterm in humans. METHODS: We examined histological sections of 20 near-term human fetuses (29-40 weeks) and those from 7 midterm fetuses (15-16 weeks). RESULTS: At midterm, the auricular cartilage was a single wavy plate with the helicis major muscle (HMM). The superior and posterior auricular muscles (SAM, PAM) were inserted into the middle parts, and the anterior auricular muscle (AAM) was inserted into the lowest part of the cartilage plate, while the tragus and antitragus were not clearly identified. In near-term fetuses, the cartilage plate varied in size and shape between specimens. The scapha and antihelix were separated from the cartilage plate with major or minor involvement of the HMM from the initial mass along the helix. The SAM inserted to the crus helix or the developing scapha, while the insertion sites of the AAM and PAM into the helix were stable. The tragus-antitragus cartilages were well-developed and they sandwiched a deep notch of skin below the helix tail. The antitragicus muscle was more evident than the tragicus muscle. An unnamed muscle was evident along the external acoustic meatus. The other intrinsic muscles, including the transverse and oblique muscles, might develop from the HMM after birth. CONCLUSIONS: Development of the auricle was advanced after midterm. However, a single wavy plate-like cartilage was maintained until late-stage. Near term, the antihelix and scapha developed from the plate-like core of the auricle and the tragus and antitragus were added in the antero-inferior side of the cartilage plate. Establishment of muscle arrangements was markedly delayed compared to cartilage development. Altogether, the classical concept of an initial funnel-like arrangement of cartilage anlagen might have been biased by studies of adult morphology.


Assuntos
Pavilhão Auricular/embriologia , Cartilagem da Orelha/embriologia , Desenvolvimento Fetal/fisiologia , Músculo Esquelético/embriologia , Idade Gestacional , Humanos
12.
Lancet Diabetes Endocrinol ; 8(4): 292-300, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135135

RESUMO

BACKGROUND: The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. METHODS: This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18-40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8-13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10-14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov, NCT00912132. FINDINGS: Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28-40 (at week 37: 3061 g [95% CI 2967-3164] for women with gestational diabetes vs 2943 g [2924-2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10-14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983-3167] in the highest tertile vs 2853 g [2755-2955] in the lowest tertile, adjusted p=0·0009. INTERPRETATION: Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24-28 gestational weeks, when gestational diabetes is typically screened for in the USA. FUNDING: National Institutes of Health.


Assuntos
Diabetes Gestacional/diagnóstico , Desenvolvimento Fetal/fisiologia , Hemoglobina A Glicada/metabolismo , Cuidado Pré-Natal/métodos , Adulto , Diabetes Gestacional/fisiopatologia , Grupos Étnicos , Feminino , Teste de Tolerância a Glucose , Humanos , Estudos Observacionais como Assunto , Gravidez , Estudos Prospectivos , Valores de Referência , Estados Unidos/epidemiologia
13.
J Pharmacol Exp Ther ; 373(2): 325-336, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32094295

RESUMO

Pre-eclampsia (PE)-induced fetal programming predisposes offspring to health hazards in adult life. Here, we tested the hypothesis that pre-eclamptic fetal programming elicits sexually dimorphic inflammatory and cardiovascular complications to endotoxemia in adult rat offspring. PE was induced by oral administration of L-NAME (50 mg/kg per day for seven consecutive days) starting from day 14 of conception. Cardiovascular studies were performed in conscious adult male and female offspring preinstrumented with femoral indwelling catheters. Compared with non-PE male counterparts, intravenous administration of lipopolysaccharide (LPS, 5 mg/kg) to PE male offspring caused significantly greater 1) falls in blood pressure, 2) increases in heart rate, 3) rises in arterial dP/dtmax, a correlate of left ventricular contractility, and 4) decreases in time- and frequency-domain indices of heart rate variability (HRV). By contrast, the hypotensive and tachycardic actions of LPS in female offspring were independent of the pre-eclamptic state and no clear changes in HRV or dP/dtmax were noted. Measurement of arterial baroreflex activity by vasoactive method revealed no sex specificity in baroreflex dysfunction induced by LPS. Immunohistochemical studies showed increased protein expression of toll-like receptor 4 in heart as well as in brainstem neuronal pools of the nucleus of solitary tract and rostral ventrolateral medulla in endotoxic PE male, but not female, offspring. Enhanced myocardial, but not neuronal, expression of monocyte chemoattractant protein-1 was also demonstrated in LPS-treated male offspring. Together, pre-eclamptic fetal programming aggravates endotoxic manifestations of hypotension and autonomic dysfunction in male offspring via exacerbating myocardial and neuromedullary inflammatory pathways. SIGNIFICANCE STATEMENT: Current molecular and neuroanatomical evidence highlights a key role for pre-eclamptic fetal programming in offspring predisposition to health hazards induced by endotoxemia in adult life. Pre-eclampsia accentuates endotoxic manifestations of hypotension, tachycardia, and cardiac autonomic dysfunction in male offspring via exacerbating myocardial and central inflammatory pathways. The absence of such detrimental effects in female littermates suggests sexual dimorphism in the interaction of pre-eclamptic fetal programming with endotoxemia.


Assuntos
Doenças Cardiovasculares/etiologia , Endotoxemia/complicações , Desenvolvimento Fetal/fisiologia , Inflamação/etiologia , Pré-Eclâmpsia/fisiopatologia , Animais , Barorreflexo/efeitos dos fármacos , Quimiocina CCL2/sangue , Feminino , Frequência Cardíaca/fisiologia , Lipopolissacarídeos/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Gravidez , Ratos , Ratos Wistar , Caracteres Sexuais
14.
Clin Neurophysiol ; 131(3): 744-749, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014681

RESUMO

OBJECTIVES: To study the association between intrauterine growth and visual pathways maturation by neonatal visual evoked potentials (VEPs) in twins, in view of a possible prognostic role. METHODS: Seventy-four twin neonates from 37 pregnancies were selected based on gestational age of more than 30 weeks and uneventful perinatal clinical course. Flash VEPs were recorded at the same postmenstrual age in each twin pair. The association between P2 latency and anthropometric variables at birth was analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins. RESULTS: Analysis of differences within each twin pair highlighted that inter-twin difference in P2 latency was significantly related to difference in ponderal index (PI) (p = 0.048). Expressing the difference in latency as a categorical binary variable, the correlation was significant for both difference in PI, (median difference = -0.36, 95% CI -0.54 to -0.14, p = 0.001) and difference in body mass index (BMI), (median difference = -1.06, 95% CI -1.74 to -0.29, p = 0.006). CONCLUSIONS: Lower values of PI and BMI differences are associated to delayed VEP latency in twin pairs. SIGNIFICANCE: VEP latency suggests reduced myelination of visual pathways when difference in growth pattern occurs in twins.


Assuntos
Desenvolvimento Infantil/fisiologia , Potenciais Evocados Visuais/fisiologia , Desenvolvimento Fetal/fisiologia , Córtex Visual/fisiologia , Eletroencefalografia , Feminino , Humanos , Recém-Nascido , Masculino , Gêmeos , Vias Visuais/fisiologia
15.
PLoS One ; 15(2): e0229568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101584

RESUMO

OBJECTIVE: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. STUDY DESIGN: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. RESULTS: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p = .19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group-SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group-SDB = 41.7% vs. No SDB = 25.0%, p = .44), nor did SDB affect the total number of decelerations overnight (HDP group-SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p = .94; control group-SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26-22.26), p = .02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p = .015) and fewer growth restricted babies at birth (30% vs. 68.4%, p = .026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. CONCLUSION: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease.


Assuntos
Hipertensão Induzida pela Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Adulto , Austrália , Peso ao Nascer , Estudos de Coortes , Feminino , Desenvolvimento Fetal/fisiologia , Retardo do Crescimento Fetal/metabolismo , Frequência Cardíaca Fetal/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Parto/fisiologia , Polissonografia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Síndromes da Apneia do Sono/complicações
16.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32108902

RESUMO

CONTEXT: Across pregnancy, maternal serum cortisol levels increase up to 3-fold. It is not known whether maternal peripheral cortisol metabolism and clearance change across pregnancy or influence fetal cortisol exposure and development. OBJECTIVES: The primary study objective was to compare maternal urinary glucocorticoid metabolites, as markers of cortisol metabolism and clearance, between the second and third trimester of pregnancy. Secondary objectives were to test associations of total maternal urinary glucocorticoid excretion, with maternal serum cortisol levels and offspring birth weight z score. DESIGN, PARTICIPANTS, AND SETTING: A total of 151 women with singleton pregnancies, recruited from prenatal clinic at the Pittsburgh site of the Measurement of Maternal Stress (MOMS) study, had 24-hour urine collections during both the second and third trimesters. RESULTS: Between the second and third trimester, total urinary glucocorticoid excretion increased (ratio of geometric means [RGM] 1.37, 95% CI 1.22-1.52, P < .001), and there was an increase in calculated 5ß-reductase compared to 5α-reductase activity (RGM 3.41, 95% CI 3.04-3.83, P < .001). During the third trimester total urinary glucocorticoid excretion and serum cortisol were negatively correlated (r = -0.179, P = .029). Mean total urinary glucocorticoid excretion across both trimesters and offspring birth weight z score were positively associated (ß = 0.314, P = .001). CONCLUSIONS: The estimated activity of maternal enzymes responsible for cortisol metabolism change between the second and third trimester of pregnancy. Additionally, maternal peripheral metabolism and clearance of cortisol may serve as a novel mechanism affecting fetal cortisol exposure and growth.


Assuntos
Glucocorticoides/urina , Hidrocortisona/sangue , Segundo Trimestre da Gravidez/metabolismo , Terceiro Trimestre da Gravidez/metabolismo , Adulto , Peso ao Nascer , Feminino , Desenvolvimento Fetal/fisiologia , Humanos , Recém-Nascido , Exposição Materna/efeitos adversos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia
17.
Sci Rep ; 10(1): 2550, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054969

RESUMO

The intrauterine and early life environments have been linked to the etiology of breast cancer in prior studies. We prospectively examined whether maternal and newborn anthropometric factors as reported by the mother are related to an increased incidence of adult breast cancer in the daughter. We used data from 35,133 mother-daughter dyads of the Nurses' Health Study (NHS) II and the Nurses' Mothers' Cohort Study. In 2001, living mothers of NHS II participants who were free of cancer completed a questionnaire on their pregnancy with the nurse and their nurse daughter's early life experience. During 403,786 years of follow-up, 865 daughters developed incident cases of invasive breast cancer. Nurses with a birthweight of ≥4000 g had a 32% greater risk for breast cancer (multivariable-adjusted hazard ratio (HR) = 1.32, 95% confidence interval (CI) = 1.02-1.71, p-trend = 0.09) compared with those with birthweights of 3000-3499 g. Higher birth length tended to increase risk of premenopausal breast cancer (p for trend = 0.05). We further noted a modest U-shaped relation between maternal weight gain during pregnancy and premenopausal breast cancer incidence in the daughter. Fetal growth may contribute to shaping later life risk for breast cancer, especially prior to menopause.


Assuntos
Neoplasias da Mama/epidemiologia , Desenvolvimento Fetal/fisiologia , Mães , Núcleo Familiar , Adulto , Antropometria , Peso ao Nascer , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Menopausa/fisiologia , Gravidez , Modelos de Riscos Proporcionais
19.
JAMA Netw Open ; 3(1): e1919940, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31995213

RESUMO

Importance: Prenatal maternal stress is increasingly associated with adverse outcomes in pregnant women and their offspring. However, the association between maternal stress and human fetal brain growth and metabolism is unknown. Objective: To identify the association between prenatal maternal psychological distress and fetal brain growth, cortical maturation, and biochemical development using advanced 3-dimensional volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS). Design, Setting, and Participants: This cohort study prospectively recruited pregnant women from low-risk obstetric clinics in Washington, DC, from January 1, 2016, to April 17, 2019. Participants were healthy volunteers with a normal prenatal medical history, no chronic or pregnancy-induced physical or mental illnesses, and normal results on fetal ultrasonography and biometry studies. Fetal brain MRI studies were performed at 2 time points between 24 and 40 weeks' gestation. Exposures: Prenatal maternal stress, anxiety, and depression. Main Outcomes and Measures: Volumes of fetal total brain, cortical gray matter, white matter, deep gray matter, cerebellum, brainstem, and hippocampus were measured from 3-dimensional reconstructed T2-weighted MRI scans. Cortical folding measurements included local gyrification index, sulcal depth, and curvedness. Fetal brain N-acetylaspartate, creatine, and choline levels were quantified using 1H-MRS. Maternal stress, depression, and anxiety were measured with the Perceived Stress Scale (PSS), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State Anxiety Inventory (SSAI), and Spielberger Trait Anxiety Inventory (STAI). Results: A total of 193 MRI studies were performed in 119 pregnant women (67 [56%] carrying male fetuses and 52 [44%], female fetuses; maternal mean [SD] age, 34.46 [5.95] years) between 24 and 40 gestational weeks. All women were high school graduates, 99 (83%) were college graduates, and 100 (84%) reported professional employment. Thirty-two women (27%) had positive scores for stress, 31 (26%) for anxiety, and 13 (11%) for depression. Maternal trait anxiety was associated with smaller fetal left hippocampal volume (STAI score: -0.002 cm3; 95% CI, -0.003 to -0.0008 cm3; P = .004). Maternal anxiety and stress were associated with increased fetal cortical gyrification in the frontal lobe (ß for SSAI score: 0.004 [95% CI, 0.001-0.006; P = .002]; ß for STAI score: 0.004 [95% CI, 0.002-0.006; P < .001]; ß for PSS score: 0.005 [95% CI, 0.001-0.008; P = .005]) and temporal lobe (ß for SSAI score: 0.004 [95% CI, 0.001-0.007; P = .004]; ß for STAI score: 0.004 [95% CI, 0.0008-0.006; P = .01]). Elevated maternal depression was associated with decreased creatine (EPDS score: -0.04; 95% CI, -0.06 to -0.02; P = .005) and choline (EPDS score: -0.03; 95% CI, -0.05 to -0.01; P = .02) levels in the fetal brain. Conclusions and Relevance: This study found that the prevalence of maternal psychological distress in healthy, well-educated, and employed pregnant women was high, underappreciated, and associated with impaired fetal brain biochemistry and hippocampal growth as well as accelerated cortical folding. These findings appear to support the need for routine mental health surveillance for all pregnant women and targeted interventions in women with elevated psychological distress.


Assuntos
Encéfalo/crescimento & desenvolvimento , Córtex Cerebral/diagnóstico por imagem , Desenvolvimento Fetal/fisiologia , Substância Cinzenta/diagnóstico por imagem , Complicações na Gravidez/diagnóstico por imagem , Estresse Psicológico/patologia , Adulto , Estudos de Coortes , Feminino , Humanos , Imageamento Tridimensional/métodos , Recém-Nascido , Imagem por Ressonância Magnética/métodos , Gravidez , Complicações na Gravidez/psicologia , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Estresse Psicológico/diagnóstico por imagem
20.
PLoS One ; 15(1): e0227872, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31978157

RESUMO

This study aimed to examine age-specific reference intervals and growth dynamics of the best fit for liver dimensions on the diaphragmatic surface of the fetal liver. The research material consisted of 69 human fetuses of both sexes (32♂, 37♀) aged 18-30 weeks. Using methods of anatomical dissection, digital image analysis and statistics, a total of 10 measurements and 2 calculations were performed. No statistical significant differences between sexes were found (p>0.05). The parameters studied displayed growth models that followed natural logarithmic functions. The mean value of the transverse-to-vertical diameter ratio of the liver throughout the analyzed period was 0.71±0.11. The isthmic ratio decreased significantly from 0.81±0.12 in the 18-19th week to 0.62±0.06 in the 26-27th week, and then increased to 0.68±0.11 in the 28-30th week of fetal life (p<0.01). The morphometric parameters of the diaphragmatic surface of the liver present age-specific reference data. No sex differences are found. The transverse-to-vertical diameter ratio supports a proportionate growth of the fetal liver. Quantitative anatomy of the growing liver may be of relevance in both the ultrasound monitoring of the fetal development and the early detection of liver anomalies.


Assuntos
Diafragma/crescimento & desenvolvimento , Desenvolvimento Fetal/fisiologia , Fígado/crescimento & desenvolvimento , Pesos e Medidas Corporais , Diafragma/diagnóstico por imagem , Feminino , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Lactente , Fígado/diagnóstico por imagem , Masculino , Tomografia Computadorizada por Raios X
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