Neonatal Stage Research Articles

Associations between per and polyfluoroalkyl ether sulfonic acids and vitamin D biomarker levels in Chinese newborns

Skeleton develops extremely fast during fetal and neonatal stages; thus, fetuses and newborns exhibit unique vulnerabilities to vitamin D metabolism dysregulation, giving vitamin D's principal role in calcium homeostasis. Previous studies linked legacy per and polyfluoroalkyl ether sulfonic acids (PFAS) with vitamin D biomarker status in adults and children; however, how PFAS, especially emerging CI-PFESAs, influence vitamin D among newborns is unknown. This study focused on the epidemiological linkages between PFAS and vitamin D biomarkers. Eleven PFAS, including legacy PFAS and emerging CI-PFESAs, as well as two vitamin D metabolites [25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3)], were determined in cord sera of 992 newborns from a birth cohort in Wuhan, China. The cord serum levels of 25(OH)D2 and 25(OH)D3 were summed as total 25(OH)D, which is a reliable biomarker of vitamin D status. The associations of separated PFAS with vitamin D biomarker levels were analyzed via multiple linear models, whereas the mixture effect was estimated by utilizing the weighted quantile sum (WQS) regression. We observed that per doubling changes in perfluorotridecanoate (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were associated with a 6.04 to 9.05 % change in total 25(OH)D levels. PFHxS contributed over half of the PFAS mixture effect on total 25(OH)D. Stratified analysis indicated that the associations of certain PFAS with vitamin D biomarkers were more pronounced among boys. The emerging CI-PFESAs were not robustly related to vitamin D biomarker levels. The results suggested that exposure to legacy PFAS might disturb vitamin D status in newborns. Future epidemiological studies are required to confirm the association and to determine healthy implications at a later age.

Developmental control of noradrenergic system by SLITRK1 and its implications in the pathophysiology of neuropsychiatric disorders.

SLITRK1 is a neuronal transmembrane protein with neurite development-and synaptic formation-controlling abilities. Several rare variants of SLITRK1 have been identified and implicated in the pathogenesis of Tourette's syndrome, trichotillomania, and obsessive-compulsive disorder, which can be collectively referred to as obsessive-compulsive-spectrum disorders. Recent studies have reported a possible association between bipolar disorder and schizophrenia, including a revertant of modern human-specific amino acid residues. Although the mechanisms underlying SLITRK1-associated neuropsychiatric disorders are yet to be fully clarified, rodent studies may provide some noteworthy clues. Slitrk1-deficient mice show neonatal dysregulation of the noradrenergic system, and later, anxiety-like behaviors that can be attenuated by an alpha 2 noradrenergic receptor agonist. The noradrenergic abnormality is characterized by the excessive growth of noradrenergic fibers and increased noradrenaline content in the medial prefrontal cortex, concomitant with enlarged serotonergic varicosities. Slitrk1 has both cell-autonomous and cell-non-autonomous functions in controlling noradrenergic fiber development, and partly alters Sema3a-mediated neurite control. These findings suggest that transiently enhanced noradrenergic signaling during the neonatal stage could cause neuroplasticity associated with neuropsychiatric disorders. Studies adopting noradrenergic signal perturbation via pharmacological or genetic means support this hypothesis. Thus, Slitrk1 is a potential candidate genetic linkage between the neonatal noradrenergic signaling and the pathophysiology of neuropsychiatric disorders involving anxiety-like or depression-like behaviors.

Layered immunity and layered leukemogenicity: Developmentally restricted mechanisms of pediatric leukemia initiation.

Hematopoietic stem cells (HSCs) and multipotent progenitor cells (MPPs) arise in successive waves during ontogeny, and their properties change significantly throughout life. Ontological changes in HSCs/MPPs underlie corresponding changes in mechanisms of pediatric leukemia initiation. As HSCs and MPPs progress from fetal to neonatal, juvenile and adult stages of life, they undergo transcriptional and epigenetic reprogramming that modifies immune output to meet age-specific pathogenic challenges. Some immune cells arise exclusively from fetal HSCs/MPPs. We propose that this layered immunity instructs cell fates that underlie a parallel layered leukemogenicity. Indeed, some pediatric leukemias, such as juvenile myelomonocytic leukemia, myeloid leukemia of Down syndrome, and infant pre-B-cell acute lymphoblastic leukemia, are age-restricted. They only present during infancy or early childhood. These leukemias likely arise from fetal progenitors that lose competence for transformation as they age. Other childhood leukemias, such as non-infant pre-B-cell acute lymphoblastic leukemia and acute myeloid leukemia, have mutation profiles that are common in childhood but rare in morphologically similar adult leukemias. These differences could reflect temporal changes in mechanisms of mutagenesis or changes in how progenitors respond to a given mutation at different ages. Interactions between leukemogenic mutations and normal developmental switches offer potential targets for therapy.

Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk.

In the thymus, cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells support αβT cell development from lymphoid progenitors. For cTECs, expression of a specialized gene signature that includes Cxcl12, Dll4, and Psmb11 enables the cortex to support T lineage commitment and the generation and selection of CD4+CD8+ thymocytes. Although the importance of cTECs in T cell development is well defined, mechanisms that shape the cTEC compartment and regulate its functional specialization are unclear. Using a Cxcl12DsRed reporter mouse model, we show that changes in Cxcl12 expression reveal a developmentally regulated program of cTEC heterogeneity. Although cTECs are uniformly Cxcl12DsRed+ during neonatal stages, progression through postnatal life triggers the appearance of Cxcl12DsRed- cTECs that continue to reside in the cortex alongside their Cxcl12DsRed+ counterparts. This appearance of Cxcl12DsRed- cTECs is controlled by maturation of CD4-CD8-, but not CD4+CD8+, thymocytes, demonstrating that stage-specific thymocyte cross-talk controls cTEC heterogeneity. Importantly, although fate-mapping experiments show both Cxcl12DsRed+ and Cxcl12DsRed- cTECs share a common Foxn1+ cell origin, RNA sequencing analysis shows Cxcl12DsRed- cTECs no longer express Foxn1, which results in loss of the FOXN1-dependent cTEC gene signature and may explain the reduced capacity of Cxcl12DsRed- cTECs for thymocyte interactions. In summary, our study shows that shaping of the cTEC compartment during the life course occurs via stage-specific thymocyte cross-talk, which drives loss of Foxn1 expression and its key target genes, which may then determine the functional competence of the thymic cortex.

Quantifying changes in umbilicus size to estimate the relative age of neonatal blacktip reef sharks (Carcharhinus melanopterus).

Sharks can incur a range of external injuries throughout their lives that originate from various sources, but some of the most notable wounds in viviparous shark neonates are at the umbilicus. Umbilical wounds typically heal within 1 to 2 months post-parturition, depending on the species, and are therefore often used as an indicator of neonatal life stage or as a relative measure of age [e.g. grouping by umbilical wound classes (UWCs), according to the size of their umbilicus]. To improve comparisons of early-life characteristics between studies, species and across populations, studies using UWCs should integrate quantitative changes. To overcome this issue, we set out to quantify changes in umbilicus size of neonatal blacktip reef sharks (Carcharhinus melanopterus) around the island of Moorea, French Polynesia, based on temporal regression relationships of umbilicus size. Here, we provide a detailed description for the construction of similar quantitative umbilical wound classifications, and we subsequently validate the accuracy of our classification and discuss two examples to illustrate its efficacy, depletion rate of maternally provided energy reserves and estimation of parturition period. A significant decrease in body condition in neonatal sharks as early as twelve days post-parturition suggests a rapid depletion of in utero-allocated energy reserves stored in the liver. Back calculations of timing of birth based on the umbilicus size of neonates determine a parturition season from September to January, with most parturitions occurring during October and November. As such, this study contributes valuable data to inform the conservation and management of young-of-the-year blacktip reef sharks, and we therefore encourage the construction and use of similar regression relationships for other viviparous shark species.

A convolutional neural network-based decision support system for neonatal quiet sleep detection.

Sleep plays an important role in neonatal brain and physical development, making its detection and characterization important for assessing early-stage development. In this study, we propose an automatic and computationally efficient algorithm to detect neonatal quiet sleep (QS) using a convolutional neural network (CNN). Our study used 38-hours of electroencephalography (EEG) recordings, collected from 19 neonates at Fudan Children's Hospital in Shanghai, China (Approval No. (2020) 22). To train and test the CNN, we extracted 12 prominent time and frequency domain features from 9 bipolar EEG channels. The CNN architecture comprised two convolutional layers with pooling and rectified linear unit (ReLU) activation. Additionally, a smoothing filter was applied to hold the sleep stage for 3 minutes. Through performance testing, our proposed method achieved impressive results, with 94.07% accuracy, 89.70% sensitivity, 94.40% specificity, 79.82% F1-score and a 0.74 kappa coefficient when compared to human expert annotations. A notable advantage of our approach is its computational efficiency, with the entire training and testing process requiring only 7.97 seconds. The proposed algorithm has been validated using leave one subject out (LOSO) validation, which demonstrates its consistent performance across a diverse range of neonates. Our findings highlight the potential of our algorithm for real-time neonatal sleep stage classification, offering a fast and cost-effective solution. This research opens avenues for further investigations in early-stage development monitoring and the assessment of neonatal health.

Congenital duodenal atresia. Report of a case

Introduction: congenital defects of the digestive tract constitute a wide spectrum of diseases, which include: the development of atresias or stenosis of the intestinal tract, these anatomical characteristics can cause changes throughout infancy and during the neonatal stage. Most of the digestive malformations present are caused by genetic changes or syndromes, their diagnosis is made in the prenatal or neonatal period, mainly in cases with complete occlusion, while those with incomplete occlusion are diagnosed laterCase presentation: a 25 year old second gestation patient with no obstetric history attended her subsequent control at 20 weeks of gestation, presenting as a physical examination finding a fundal height discordant with gestational age by date of last menstrual period, which is why obstetric ultrasound was requested, At 28 weeks due to the onset of labor it was decided to terminate the pregnancy, due to premature product, the patient was admitted to the neonatology ward and after 10 days was operated by means of an open laparotomy, a procedure without complications.Conclusions: subsequent obstetric follow-up will allow timely diagnosis and treatment to improve the long-term prognosis

Single-cell transcriptomic analysis identifies murine heart molecular features at embryonic and neonatal stages

Heart development is a continuous process involving significant remodeling during embryogenesis and neonatal stages. To date, several groups have used single-cell sequencing to characterize the heart transcriptomes but failed to capture the progression of heart development at most stages. This has left gaps in understanding the contribution of each cell type across cardiac development. Here, we report the transcriptional profile of the murine heart from early embryogenesis to late neonatal stages. Through further analysis of this dataset, we identify several transcriptional features. We identify gene expression modules enriched at early embryonic and neonatal stages; multiple cell types in the left and right atriums are transcriptionally distinct at neonatal stages; many congenital heart defect-associated genes have cell type-specific expression; stage-unique ligand-receptor interactions are mostly between epicardial cells and other cell types at neonatal stages; and mutants of epicardium-expressed genes Wt1 and Tbx18 have different heart defects. Assessment of this dataset serves as an invaluable source of information for studies of heart development.

279. Maternal Infection by SARS CoV2 and Clinical Repercussion of the Newborn.

Abstract Background Pregnancy confers a higher risk of complications in SARS CoV2 disease as well as in the neonatal stage. Physiological and immunological changes during pregnancy predispose women to have complications in all the respiratory variations and increase maternal-fetal mortality and morbidity; The role of SARS CoV2 infection in newborns of mothers positive for COVID-19 was evaluated, analyzing the clinical consequences in the pregnant patient and the impact on the newborn. Methods Descriptive, observational, retrospective study. All pregnant patients with a positive PCR test for SARS CoV2 and newborns treated at the Spanish Hospital, in the period from March 2020 to March 2021, were included, the information provided was collected from the medical history. Results We recorded the cases of pregnant patients treated at the Spanish Hospital in the period from March 2020 to March 2021. The population was divided into those with a positive and negative PCR test for SARS Cov2. A total of 561 cases were registered, 35 positive cases for SARS Cov2; positive patients reported a higher presentation of Preeclampsia than patients without infection (p 0.009). The percentage of preterm products in mothers with infection was higher by 20% vs 12%; with the highest number of advanced neonatal resuscitation events. SARS Cov2 infection conditions the presentation of pathologies such as preeclampsia in pregnant women and an increase in preterm birth. Conclusion In this study we conclude, comparing with the group of healthy pregnant women with no history of COVID-19, that the products of mothers with a history of SARS CoV2 infection represent a higher risk of prematurity coupled with the risk of other pathologies such as preeclampsia, also in the period neonatal patients required greater support with oxygen, however the rate of severe complications in the newborn is unlikely. The role of maternal protection such as isolation, hygiene and vaccination measures are priority tools to reduce these perinatal pathologies and the risk of contagion. Disclosures All Authors: No reported disclosures.

Ability of the Right Ventricle to Serve as a Systemic Ventricle in Response to the Volume Overload at the Neonatal Stage.

In children with hypoplastic left heart syndrome (HLHS), volume overload (VO) is inevitable, and the right ventricle (RV) pumps blood into the systemic circulation. Understanding the molecular differences and their different responses to VO between the RV and left ventricle (LV) at the neonatal and highly plastic stages may improve the long-term management of children with HLHS. A neonatal rat ventricular VO model was established by the creation of a fistula between the inferior vena cava and the abdominal aorta on postnatal day 1 (P1) and confirmed by echocardiographic and histopathological analyses. Transcriptomic analysis demonstrated that some of the major differences between a normal neonatal RV and LV were associated with the thyroid hormone and insulin signaling pathways. Under the influence of VO, the levels of insulin receptors and thyroid hormone receptors were significantly increased in the LV but decreased in the RV. The transcriptomic analysis also demonstrated that under the influence of VO, the top two common enriched pathways between the RV and LV were the insulin and thyroid hormone signaling pathways, whereas the RV-specific enriched pathways were primarily associated with lipid metabolism and arrhythmogenic right ventricular cardiomyopathy (ARVC); further, the LV-specific enriched pathways were primarily associated with nucleic acid metabolism and microRNAs in cancer. Insulin and thyroid hormones may play critical roles in the differences between a neonatal RV and LV as well as their common responses to VO. Regarding the isolated responses to VO, the RV favors an ARVC change and the LV favors a reduction in microRNAs in cancer. The current study suggests that insulin, thyroid hormone, and cancer-associated microRNAs are potential therapeutic targets that should be explored by basic science studies to improve the function of the RV to match that of the LV.

Metabolic reprogramming and membrane glycan remodeling as potential drivers of zebrafish heart regeneration

The ability of the zebrafish heart to regenerate following injury makes it a valuable model to deduce why this capability in mammals is limited to early neonatal stages. Although metabolic reprogramming and glycosylation remodeling have emerged as key aspects in many biological processes, how they may trigger a cardiac regenerative response in zebrafish is still a crucial question. Here, by using an up-to-date panel of transcriptomic, proteomic and glycomic approaches, we identify a metabolic switch from mitochondrial oxidative phosphorylation to glycolysis associated with membrane glycosylation remodeling during heart regeneration. Importantly, we establish the N- and O-linked glycan structural repertoire of the regenerating zebrafish heart, and link alterations in both sialylation and high mannose structures across the phases of regeneration. Our results show that metabolic reprogramming and glycan structural remodeling are potential drivers of tissue regeneration after cardiac injury, providing the biological rationale to develop novel therapeutics to elicit heart regeneration in mammals.

Spatiotemporal dynamics of 5-HT6 receptor ciliary localization during mouse brain development

The serotonin 5-HT6 receptor (5-HT6R) is a promising target to improve cognitive symptoms of psychiatric diseases of neurodevelopmental origin, such as autism spectrum disorders and schizophrenia. However, its expression and localization at different stages of brain development remain largely unknown, due to the lack of specific antibodies to detect endogenous 5-HT6R. Here, we used transgenic mice expressing a GFP-tagged 5-HT6R under the control of its endogenous promoter (Knock-in) as well as embryonic stem cells expressing the GFP-tagged receptor to extensively characterize its expression at cellular and subcellular levels during development. We show that the receptor is already expressed at E13.5 in the cortex, the striatum, the ventricular zone, and to a lesser extent the subventricular zone. In adulthood, it is preferentially found in projection neurons of the hippocampus and cerebral cortex, in striatal medium-sized spiny neurons, as well as in a large proportion of astrocytes, while it is expressed in a minor population of interneurons. Whereas the receptor is almost exclusively detected in the primary cilia of neurons at embryonic and adult stages and in differentiated stem cells, it is located in the somatodendritic compartment of neurons from some brain regions at the neonatal stage and in the soma of undifferentiated stem cells. Finally, knocking-out the receptor induces a shortening of the primary cilium, suggesting that it plays a role in its function. This study provides the first global picture of 5-HT6R expression pattern in the mouse brain at different developmental stages. It reveals dynamic changes in receptor localization in neurons at the neonatal stage, which might underlie its key role in neuronal differentiation and psychiatric disorders of neurodevelopmental origin.

A mitofusin 2/HIF1α axis sets a maturation checkpoint in regenerating skeletal muscle.

A fundamental issue in regenerative medicine is whether there exist endogenous regulatory mechanisms that limit the speed and efficiency of the repair process. We report the existence of a maturation checkpoint during muscle regeneration that pauses myofibers at a neonatal stage. This checkpoint is regulated by the mitochondrial protein mitofusin 2 (Mfn2), the expression of which is activated in response to muscle injury. Mfn2 is required for growth and maturation of regenerating myofibers; in the absence of Mfn2, new myofibers arrested at a neonatal stage, characterized by centrally nucleated myofibers and loss of H3K27me3 repressive marks at the neonatal myosin heavy chain gene. A similar arrest at the neonatal stage was observed in infantile cases of human centronuclear myopathy. Mechanistically, Mfn2 upregulation suppressed expression of hypoxia-induced factor 1α (HIF1α), which is induced in the setting of muscle damage. Sustained HIF1α signaling blocked maturation of new myofibers at the neonatal-to-adult fate transition, revealing the existence of a checkpoint that delays muscle regeneration. Correspondingly, inhibition of HIF1α allowed myofibers to bypass the checkpoint, thereby accelerating the repair process. We conclude that skeletal muscle contains a regenerative checkpoint that regulates the speed of myofiber maturation in response to Mfn2 and HIF1α activity.

Temporal molecular program of human hematopoietic stem and progenitor cells after birth.

Hematopoietic stem and progenitor cells (HSPCs) give rise to the blood system and maintain hematopoiesis throughout the human lifespan. Here, we report a transcriptional census of human bone-marrow-derived HSPCs from the neonate, infant, child, adult, and aging stages, showing two subpopulations of multipotent progenitors separated by CD52 expression. From birth to the adult stage, stem and multipotent progenitors shared similar transcriptional alterations, and erythroid potential was enhanced after the infant stage. By integrating transcriptome, chromatin accessibility, and functional data, we further showed that aging hematopoietic stem cells (HSCs) exhibited a bias toward megakaryocytic differentiation. Finally, in comparison with the HSCs from the cord blood, neonate bone-marrow-derived HSCs were more quiescent and had higher long-term regeneration capability and durable self-renewal. Taken together, this work provides an integral transcriptome landscape of HSPCs and identifies their dynamics in post-natal steady-state hemopoiesis, thereby helping explore hematopoiesis in development and diseases.

Gabrb3 is required for the functional integration of pyramidal neuron subtypes in the somatosensory cortex

Dysfunction of gamma-aminobutyric acid (GABA)ergic circuits is strongly associated with neurodevelopmental disorders. However, it is unclear how genetic predispositions impact circuit assembly. Using invivo two-photon and widefield calcium imaging in developing mice, we show that Gabrb3, a gene strongly associated with autism spectrum disorder (ASD) and Angelman syndrome (AS), is enriched in contralaterally projecting pyramidal neurons and is required for inhibitory function. We report that Gabrb3 ablation leads to a developmental decrease in GABAergic synapses, increased local network synchrony, and long-lasting enhancement in functional connectivity of contralateral-but not ipsilateral-pyramidal neuron subtypes. In addition, Gabrb3 deletion leads to increased cortical response to tactile stimulation at neonatal stages. Using human transcriptomics and neuroimaging datasets from ASD subjects, we show that the spatial distribution of GABRB3 expression correlates with atypical connectivity in these subjects. Our studies reveal a requirement for Gabrb3 during the emergence of interhemispheric circuits for sensory processing.

Complexity of modular neuromuscular control increases and variability decreases during human locomotor development

When does modular control of locomotion emerge during human development? One view is that modularity is not innate, being learnt over several months of experience. Alternatively, the basic motor modules are present at birth, but are subsequently reconfigured due to changing brain-body-environment interactions. One problem in identifying modular structures in stepping infants is the presence of noise. Here, using both simulated and experimental muscle activity data from stepping neonates, infants, preschoolers, and adults, we dissect the influence of noise, and identify modular structures in all individuals, including neonates. Complexity of modularity increases from the neonatal stage to adulthood at multiple levels of the motor infrastructure, from the intrinsic rhythmicity measured at the level of individual muscles activities, to the level of muscle synergies and of bilateral intermuscular network connectivity. Low complexity and high variability of neuromuscular signals attest neonatal immaturity, but they also involve potential benefits for learning locomotor tasks.

Impact of Physiologically Relevant Genistein Exposure at Different Time Windows on Puberty Onset and Neuroendocrine Function in Female Rats.

Puberty timing, critical for adulthood wellbeing, is influenced by the environment, life-style, and diets. However, differential puberty-interfering effects of soy and soy isoflavone are observed in both epidemiological and toxicological studies. Additionally, their impact on neuroendocrine function at various pre-pubertal developmental windows is unclear. This study investigates the effect of genistein, a typical soy isoflavone, at neonatal, lactational, and post-weaning stages on the time of vaginal opening and determines the levels of neuroendocrine factors in female rats using immunofluorescence, immunochemistry, and enzyme-linked immunosorbent assays. A physiologically relevant dosage (10mgkg-1 ) is used to resemble human exposure. The results show that genistein exposure at lactational stage significantly accelerates vaginal opening time, marginally increases hypothalamic gonadotropin-releasing hormone (GnRH) secretion, significantly enhances kisspeptin receptor expression, and markedly elevates blood levels of GnRH, luteinizing hormone, and follicle-stimulating hormone, while neonatal and post-weaning exposures do not induce significant alternations. Lactational stage may be an important window for genistein to impact reproductive development and neuroendocrine regulations.

BMP10 functions independently from BMP9 for the development of a proper arteriovenous network

Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs. HHT is caused by mutations in genes encoding major constituents for transforming growth factor-β (TGF-β) family signaling: endoglin (ENG), activin receptor-like kinase 1 (ALK1), and SMAD4. The identity of physiological ligands for this ENG-ALK1 signaling pertinent to AVM formation has yet to be clearly determined. To investigate whether bone morphogenetic protein 9 (BMP9), BMP10, or both are physiological ligands of ENG-ALK1 signaling involved in arteriovenous network formation, we generated a novel Bmp10 conditional knockout mouse strain. We examined whether global Bmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control, Bmp9-KO, and Bmp9/10-double KO (dKO) mice. Bmp10-iKO and Bmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, while Bmp9-KO did not display any noticeable vascular defects. Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina of Bmp10-iKO and Bmp9/10-dKO mice was detected. Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar to Bmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.

Description of neonate of the freckled sand skate Psammobatis lentiginosa and observations on incubation period

Some of the characters used in description and identification keys for skates are mostly valid for adults, and may dramatically change through ontogeny. The lack of morphological description of the neonate stage prevents from identifying them in nature. Two neonates of Psammobatis lentiginosa born in captivity and three collected from the wild were used in this study. Morphometric differences were found in distance between orbits, distance between first gill slits and epichordal lobe. Colour pattern and spinulation presented differences as well. Observations on incubation period were taken. Hatching occurred 130 days after egg case collection.

Selective IgA Deficiency in Spontaneously Hypertensive Rats With Gut Dysbiosis.

The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR. IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin). Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP. This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.