ResearchPad - Developmental Biology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The role of SUMOylation during development]]> https://www.researchpad.co/product?articleinfo=N2d803150-5475-42d7-89a4-9a275ef06444

During the development of multicellular organisms, transcriptional regulation plays an important role in the control of cell growth, differentiation and morphogenesis. SUMOylation is a reversible post-translational process involved in transcriptional regulation through the modification of transcription factors and through chromatin remodelling (either modifying chromatin remodelers or acting as a ‘molecular glue’ by promoting recruitment of chromatin regulators). SUMO modification results in changes in the activity, stability, interactions or localization of its substrates, which affects cellular processes such as cell cycle progression, DNA maintenance and repair or nucleocytoplasmic transport. This review focuses on the role of SUMO machinery and the modification of target proteins during embryonic development and organogenesis of animals, from invertebrates to mammals.

]]>
<![CDATA[A mammalian Wnt5a–Ror2–Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis]]> https://www.researchpad.co/product?articleinfo=N91110499-c0a8-46e7-9697-e8de354da835

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a–Ror2–Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior.

]]>
<![CDATA[Adult chondrogenesis and spontaneous cartilage repair in the skate, Leucoraja erinacea]]> https://www.researchpad.co/product?articleinfo=N3c1ff317-0898-4a93-a54f-455b67f535d1

Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.

]]>
<![CDATA[Mechanical stimulation induced osteogenic differentiation of BMSCs through TWIST/E2A/p21 axis]]> https://www.researchpad.co/product?articleinfo=N165f4d50-caca-4f6d-98e3-7798e10e9569

Abstract

The relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.

]]>
<![CDATA[Extending thermotolerance to tomato seedlings by inoculation with SA1 isolate of Bacillus cereus and comparison with exogenous humic acid application]]> https://www.researchpad.co/product?articleinfo=N5b151d82-6b14-4a7f-beb8-82f649a56498

Heat stress is one of the major abiotic stresses that impair plant growth and crop productivity. Plant growth-promoting endophytic bacteria (PGPEB) and humic acid (HA) are used as bio-stimulants and ecofriendly approaches to improve agriculture crop production and counteract the negative effects of heat stress. Current study aimed to analyze the effect of thermotolerant SA1 an isolate of Bacillus cereus and HA on tomato seedlings. The results showed that combine application of SA1+HA significantly improved the biomass and chlorophyll fluorescence of tomato plants under normal and heat stress conditions. Heat stress increased abscisic acid (ABA) and reduced salicylic acid (SA) content; however, combined application of SA1+HA markedly reduced ABA and increased SA. Antioxidant enzymes activities revealed that SA1 and HA treated plants exhibited increased levels of ascorbate peroxidase (APX), superoxide dismutase (SOD), and reduced glutathione (GSH). In addition, heat stress markedly reduced the amino acid contents; however, the amino acids were increased with co-application of SA1+HA. Similarly, inductively-coupled plasma mass-spectrometry results showed that plants treated with SA1+HA exhibited significantly higher iron (Fe+), phosphorus (P), and potassium (K+) uptake during heat stress. Heat stress increased the relative expression of SlWRKY33b and autophagy-related (SlATG5) genes, whereas co-application of SA1+HA augmented the heat stress response and reduced SlWRKY33b and SlATG5 expression. The heat stress-responsive transcription factor (SlHsfA1a) and high-affinity potassium transporter (SlHKT1) were upregulated in SA1+HA-treated plants. In conclusion, current findings suggest that co-application with SA1+HA can be used for the mitigation of heat stress damage in tomato plants and can be commercialized as a biofertilizer.

]]>
<![CDATA[Enhanced genome editing in human iPSCs with CRISPR-CAS9 by co-targeting ATP1a1]]> https://www.researchpad.co/product?articleinfo=N15f2ecb1-82df-41f3-9520-a4bd60a5f2fe

Genome editing in human induced pluripotent stem cells (iPSCs) provides the potential for disease modeling and cell therapy. By generating iPSCs with specific mutations, researchers can differentiate the modified cells to their lineage of interest for further investigation. However, the low efficiency of targeting in iPSCs has hampered the application of genome editing. In this study we used a CRISPR-Cas9 system that introduces a specific point substitution into the sequence of the Na+/K+-ATPase subunit ATP1A1. The introduced mutation confers resistance to cardiac glycosides, which can then be used to select successfully targeted cells. Using this system, we introduced different formats of donor DNA for homology-directed repair (HDR), including single-strand DNAs, double-strand DNAs, and plasmid donors. We achieved a 35-fold increase in HDR when using plasmid donor with a 400 bp repair template. We further co-targeted ATP1A1 and a second locus of interest to determine the enrichment of mutagenesis after cardiac glycoside selection. Through this approach, INDEL rate was increased after cardiac glycoside treatment, while HDR enrichment was only observed at certain loci. Collectively, these results suggest that a plasmid donor with a 400 bp repair template is an optimal donor DNA for targeted substitution and co-targeting ATP1A1 with the second locus enriches for mutagenesis events through cardiac glycoside selection in human iPSCs.

]]>
<![CDATA[Temporal integration of auxin information for the regulation of patterning]]> https://www.researchpad.co/product?articleinfo=N630dfd83-b60b-487d-a7ae-ae424186a4cf

Positional information is essential for coordinating the development of multicellular organisms. In plants, positional information provided by the hormone auxin regulates rhythmic organ production at the shoot apex, but the spatio-temporal dynamics of auxin gradients is unknown. We used quantitative imaging to demonstrate that auxin carries high-definition graded information not only in space but also in time. We show that, during organogenesis, temporal patterns of auxin arise from rhythmic centrifugal waves of high auxin travelling through the tissue faster than growth. We further demonstrate that temporal integration of auxin concentration is required to trigger the auxin-dependent transcription associated with organogenesis. This provides a mechanism to temporally differentiate sites of organ initiation and exemplifies how spatio-temporal positional information can be used to create rhythmicity.

]]>
<![CDATA[Molecular Insights Into Therapeutic Potential of Autophagy Modulation by Natural Products for Cancer Stem Cells]]> https://www.researchpad.co/product?articleinfo=N83c4b782-6563-4621-8951-29391cea7a17

Autophagy, a cellular self-digestion process that is activated in response to stress, has a functional role in tumor formation and progression. Cancer stem cells (CSCs) accounting for a minor proportion of total cancer cells-have distinct self-renewal and differentiation abilities and promote metastasis. Researchers have shown that a numeral number of natural products using traditional experimental methods have been revealed to target CSCs. However, the specific role of autophagy with respect to CSCs and tumorigenesis using natural products are still unknown. Currently, CSCs are considered to be one of the causative reasons underlying the failure of anticancer treatment as a result of tumor recurrence, metastasis, and chemo- or radio-resistance. Autophagy may play a dual role in CSC-related resistance to anticancer treatment; it is responsible for cell fate determination and the targeted degradation of transcription factors via growth arrest. It has been established that autophagy promotes drug resistance, dormancy, and stemness and maintenance of CSCs. Surprisingly, numerous studies have also suggested that autophagy can facilitate the loss of stemness in CSCs. Here, we review current progress in research related to the multifaceted connections between autophagy modulation and CSCs control using natural products. Overall, we emphasize the importance of understanding the role of autophagy in the maintenance of different CSCs and implications of this connection for the development of new strategies for cancer treatment targeting natural products.

]]>
<![CDATA[Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice]]> https://www.researchpad.co/product?articleinfo=N7e089ef3-cdb3-4902-9d09-74f164ea37a0

Significance

As the human body is composed of 60 trillion cells that originate from a fertilized egg, sperm–oocyte fusion is the initial event of our life. Few sperm–oocyte fusion factors have been unveiled to date, and only IZUMO1 has been identified as a sperm-specific fusion-mediating protein. Here, we identified the testis-specific 4930451I11Rik gene important for male fertility, playing a role in sperm–oocyte fusion during fertilization. Based on its functional role, we renamed this gene fertilization influencing membrane protein (Fimp). We discovered a factor responsible for sperm–oocyte fusion in mammals, and this knowledge could be used to develop in vitro and in vivo infertility treatments as well as male contraceptives.

]]>
<![CDATA[JNK-dependent intestinal barrier failure disrupts host–microbe homeostasis during tumorigenesis]]> https://www.researchpad.co/product?articleinfo=N219ffc0c-4077-4705-967b-51b558fe4c80

Significance

The intestinal epithelium forms a tight barrier to the environment and is constantly regenerated. Precise control of barrier function and tissue renewal is important to maintain homeostasis. Using an inducible tumor model in the Drosophila intestine, this study shows that tumor progression disrupts the intestinal barrier and leads to commensal dysbiosis, thereby further fueling tumor growth. This reenforcing feedback loop can be interrupted by treatments with JNK inhibitor or antibiotics.

]]>
<![CDATA[Protein phosphatase 1 activity controls a balance between collective and single cell modes of migration]]> https://www.researchpad.co/product?articleinfo=Neec4725b-f287-45ea-98b2-be458703a041

Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep cell collectives together and coordinate movement of multiple cells are poorly understood. Using the Drosophila border cell migration model, we find that Protein phosphatase 1 (Pp1) activity controls collective cell cohesion and migration. Inhibition of Pp1 causes border cells to round up, dissociate, and move as single cells with altered motility. We present evidence that Pp1 promotes proper levels of cadherin-catenin complex proteins at cell-cell junctions within the cluster to keep border cells together. Pp1 further restricts actomyosin contractility to the cluster periphery rather than at individual internal border cell contacts. We show that the myosin phosphatase Pp1 complex, which inhibits non-muscle myosin-II (Myo-II) activity, coordinates border cell shape and cluster cohesion. Given the high conservation of Pp1 complexes, this study identifies Pp1 as a major regulator of collective versus single cell migration.

]]>
<![CDATA[Defects in mTORC1 Network and mTORC1-STAT3 Pathway Crosstalk Contributes to Non-inflammatory Hepatocellular Carcinoma]]> https://www.researchpad.co/product?articleinfo=N437821a0-254b-4bdf-86cb-35bfdf3c2d8a

Background and Aims

Mammalian target of rapamycin complex 1 (mTORC1) is frequently hyperactivated in hepatocellular carcinoma (HCC). Cases of HCC without inflammation and cirrhosis are not rarely seen in clinics. However, the molecular basis of non-inflammatory HCC remains unclear.

Methods

Spontaneous non-inflammatory HCC in mice was triggered by constitutive elevation of mTORC1 by liver-specific TSC1 knockout (LTsc1KO). A multi-omics approach was utilized on tumor tissues to better understand the molecular basis for the development of HCC in the LTsc1KO model.

Results

We showed that LTsc1KO in mice triggered spontaneous non-inflammatory HCC, with molecular characteristics similar to those of diethylnitrosamine-mediated non-cirrhotic HCC. Mitochondrial and autophagy defects, as well as hepatic metabolic disorder were manifested in HCC development by LTsc1KO. mTORC1 activation on its own regulated an oncogenic network (DNA-damage-inducible transcript 4, nuclear protein 1, and fibroblast growth factor 21), and mTORC1–signal transducer and activator of transcription pathway crosstalk that altered specific metabolic pathways contributed to the development of non-inflammatory HCC.

Conclusion

Our findings reveal the mechanisms of mTORC1-driven non-inflammatory HCC and provide insight into further development of a protective strategy against non-inflammatory HCC.

]]>
<![CDATA[ESCRT Machinery Mediates Cytokinetic Abscission in the Unicellular Red Alga Cyanidioschyzon merolae]]> https://www.researchpad.co/product?articleinfo=Ne8860ae4-5e79-467c-af9a-3f75cbe4bdb2

In many eukaryotes, cytokinesis proceeds in two successive steps: first, ingression of the cleavage furrow and second, abscission of the intercellular bridge. In animal cells, the actomyosin contractile ring is involved in the first step, while the endosomal sorting complex required for transport (ESCRT), which participates in various membrane fusion/fission events, mediates the second step. Intriguingly, in archaea, ESCRT is involved in cytokinesis, raising the hypothesis that the function of ESCRT in eukaryotic cytokinesis descended from the archaeal ancestor. In eukaryotes other than in animals, the roles of ESCRT in cytokinesis are poorly understood. To explore the primordial core mechanisms for eukaryotic cytokinesis, we investigated ESCRT functions in the unicellular red alga Cyanidioschyzon merolae that diverged early in eukaryotic evolution. C. merolae provides an excellent experimental system. The cell has a simple organelle composition. The genome (16.5 Mb, 5335 genes) has been completely sequenced, transformation methods are established, and the cell cycle is synchronized by a light and dark cycle. Similar to animal and fungal cells, C. merolae cells divide by furrowing at the division site followed by abscission of the intercellular bridge. However, they lack an actomyosin contractile ring. The proteins that comprise ESCRT-I–IV, the four subcomplexes of ESCRT, are partially conserved in C. merolae. Immunofluorescence of native or tagged proteins localized the homologs of the five ESCRT-III components [charged multivesicular body protein (CHMP) 1, 2, and 4–6], apoptosis-linked gene-2-interacting protein X (ALIX), the ESCRT-III adapter, and the main ESCRT-IV player vacuolar protein sorting (VPS) 4, to the intercellular bridge. In addition, ALIX was enriched around the cleavage furrow early in cytokinesis. When the ESCRT function was perturbed by expressing dominant-negative VPS4, cells with an elongated intercellular bridge accumulated—a phenotype resulting from abscission failure. Our results show that ESCRT mediates cytokinetic abscission in C. merolae. The fact that ESCRT plays a role in cytokinesis in archaea, animals, and early diverged alga C. merolae supports the hypothesis that the function of ESCRT in cytokinesis descended from archaea to a common ancestor of eukaryotes.

]]>
<![CDATA[Developmental variability channels mouse molar evolution]]> https://www.researchpad.co/product?articleinfo=N3700f8e9-fd4f-4198-80d3-1ea80bb224ac

Do developmental systems preferentially produce certain types of variation that orient phenotypic evolution along preferred directions? At different scales, from the intra-population to the interspecific, the murine first upper molar shows repeated anterior elongation. Using a novel quantitative approach to compare the development of two mouse strains with short or long molars, we identified temporal, spatial and functional differences in tooth signaling center activity, that arise from differential tuning of the activation-inhibition mechanisms underlying tooth patterning. By tracing their fate, we could explain why only the upper first molar reacts via elongation of its anterior part. Despite a lack of genetic variation, individuals of the elongated strain varied in tooth length and the temporal dynamics of their signaling centers, highlighting the intrinsic instability of the upper molar developmental system. Collectively, these results reveal the variational properties of murine molar development that drive morphological evolution along a line of least resistance.

]]>
<![CDATA[Chloride channels regulate differentiation and barrier functions of the mammalian airway]]> https://www.researchpad.co/product?articleinfo=Nbdbded91-ef81-4231-bfdf-e805fa490a87

The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. The molecular events required for the formation and function of the airway mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway diseases, remain unclear. In this study, we systematically characterized the developmental landscape of the mouse airway using single-cell RNA sequencing and identified remarkably conserved cellular programs operating during human fetal development. We demonstrated that in mouse, genetic inactivation of chloride channel Ano1/Tmem16a compromises airway barrier function, results in early signs of inflammation, and alters the airway cellular landscape by depleting epithelial progenitors. Mouse Ano1-/-mutants exhibited mucus obstruction and abnormal mucociliary clearance that resemble the airway defects associated with cystic fibrosis. The data reveal critical and non-redundant roles for Ano1 in organogenesis, and show that chloride channels are essential for mammalian airway formation and function.

]]>
<![CDATA[Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila]]> https://www.researchpad.co/product?articleinfo=Na2584fde-7193-4214-9307-babfd149176b

Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD.

]]>
<![CDATA[Condensin I subunit Cap-G is essential for proper gene expression during the maturation of post-mitotic neurons]]> https://www.researchpad.co/product?articleinfo=N143909ec-2052-404c-8567-7e380d515a3a

Condensin complexes are essential for mitotic chromosome assembly and segregation during cell divisions, however, little is known about their functions in post-mitotic cells. Here we report a role for the condensin I subunit Cap-G in Drosophila neurons. We show that, despite not requiring condensin for mitotic chromosome compaction, post-mitotic neurons express Cap-G. Knockdown of Cap-G specifically in neurons (from their birth onwards) results in developmental arrest, behavioural defects, and dramatic gene expression changes, including reduced expression of a subset of neuronal genes and aberrant expression of genes that are not normally expressed in the developing brain. Knockdown of Cap-G in mature neurons results in similar phenotypes but to a lesser degree. Furthermore, we see dynamic binding of Cap-G at distinct loci in progenitor cells and differentiated neurons. Therefore, Cap-G is essential for proper gene expression in neurons and plays an important role during the early stages of neuronal development.

]]>
<![CDATA[Uptake and speciation of zinc in edible plants grown in smelter contaminated soils]]> https://www.researchpad.co/product?articleinfo=N21b4cc8f-fdc5-4198-8cfa-2868c1971919

Heavy metal accumulation in edible plants grown in contaminated soils poses a major environmental risk to humans and grazing animals. This study focused on the concentration and speciation of Zn in different edible plants grown in soils contaminated with smelter wastes (Spelter, WV, USA) containing high levels of the metals Zn, Cu, Pb, Cd. Their accumulation was examined in different parts (roots, stem, and leaves) of plants and as a function of growth stage (dry seed, sprouting seed, cotyledon, and leaves) in the root vegetables radish, the leafy vegetable spinach and the legume clover. Although the accumulation of metals varied significantly with plant species, the average metal concentrations were [Zn] > [Pb] > [Cu] > [Cd]. Metal uptake studies were complemented with bulk and micro X-ray absorption spectroscopy (XAS) at Zn K-edge and micro X-ray fluorescence (μXRF) measurements to evaluate the speciation and distribution of Zn in these plant species. Dynamic interplay between the histidine and malate complexation of Zn was observed in all plant species. XRF mapping of spinach leaves at micron spatial resolution demonstrated the accumulation of Zn in vacuoles and leaf tips. Radish root showed accumulation of Zn in root hairs, likely as ZnS nanoparticles. At locations of high Zn concentration in spinach leaves, μXANES suggests Zn complexation with histidine, as opposed to malate in the bulk leaf. These findings shed new light on the dynamic nature of Zn speciation in plants.

]]>
<![CDATA[Toward precision prescribing for methadone: Determinants of methadone deposition]]> https://www.researchpad.co/product?articleinfo=N51499fe4-a854-40f2-ac0e-5bd2b114360f

Background

Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism.

Methods

We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants.

Results

Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI.

Conclusions

Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

]]>
<![CDATA[Exposure to dim light at night prior to conception attenuates offspring innate immune responses]]> https://www.researchpad.co/product?articleinfo=N231fece1-eb24-47b2-a00f-cbdce7a093c6

Functional circadian timekeeping is necessary for homeostatic control of the immune system and appropriate immune responsiveness. Disruption of natural light-dark cycles, through light at night (LAN), impairs innate and adaptive immune responses in nocturnal rodents. These altered immune responses are associated with disrupted endogenous gene transcriptional and endocrine cycles. However, few studies have addressed the multigenerational consequences of systemic circadian rhythm disruption. We hypothesized that parental exposure to dim LAN (dLAN) would alter innate immune and sickness responses to an endotoxin challenge in adult offspring gestated and reared in dark nights. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 8 weeks, then paired, mated, and thereafter housed under dark nights. Maternal exposure to dLAN prior to conception impaired febrile responses and increased splenic il-1 production in response to LPS in male offspring. Paternal pre-conception dLAN dampened offspring tnf-α expression in the hypothalamus, reduced serum bactericidal capacity, and dark phase locomotor activity. These changes occurred despite offspring being conceived, gestated, and reared under standard dark night conditions. Overall, these data suggest that dLAN has intergenerational effects on innate immunity and sickness responses.

]]>