EVs Containing Host Restriction Factor IFITM3 Inhibited ZIKV Infection of Fetuses in Pregnant Mice through Trans-placenta Delivery.
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ABSTRACT:
SUBMITTER: Zou X
PROVIDER: S-EPMC7791082 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats.MethodsFemale Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85-90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples.ResultsMaternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart.ConclusionsMaternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated.
| S-EPMC4643918 | biostudies-literature
Project description:Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n = 6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n = 3 for FP isolate H/PF/2013; n = 3 for PR isolate PRVABC59) at midgestation (86 to 95 days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n = 5) or 39 days (n = 1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.
| S-EPMC7269433 | biostudies-literature
Project description:BackgroundThis study aims to investigate galectin-1 (Gal-1) expression in the serum and placenta of pregnant women with fetal growth restriction (FGR) and its significance.MethodsThirty-one pregnant women with single-birth FGR but without comorbidities, eight pregnant women with FGR and preeclampsia (PE), and eight pregnant women with FGR and gestational diabetes mellitus (GDM) were enrolled as the study group, while 20 pregnant women with normal singleton pregnancy in the same period were enrolled as the control group. The serum Gal-1 level was detected using an enzyme-linked immunosorbent assay (ELISA), and Gal-1 expression in the placenta was detected by western blot.ResultsThe results revealed that, compared with the control group, the serum Gal-1 level decreased in the women with FGR without comorbidities, and the difference was statistically significant (P?<?0.001). Compared with the control group, the difference in serum Gal-1 expression in the FGR-PE group was not statistically significant (P?=?0.29). The peripheral serum Gal-1 level decreased in the FGR-GDM group compared with the control group, and the difference was statistically significant (P?<?0.001). The serum Gal-1 level was positively correlated with birth weight (r2?=?0.172, P?<?0.01). Compared with the control group, the Gal-1 expression level decreased in the placenta of the pregnant women with FGR without comorbidities (P?<?0.05).ConclusionsGal-1 exhibits low expression in the serum and placenta of pregnant women with FGR. In addition, Gal-1 may be involved in the pathogenesis of FGR and could represent a new diagnostic marker of the disease.
| S-EPMC7789211 | biostudies-literature
Project description:Here we use a proteomic approach to study the role of the placenta in ZIKV-induced microcephaly and the mechanisms of ZIKV to cross the placental barrier. Samples were separated into three groups: an uninfected control group (ZIKV-CZS-), a group of placentas infected by ZIKV with normal neonates (ZIKV+CZS-), and a group of placentas infected by ZIKV that developed microcephaly in newborns (ZIKV+CZS+). Zika virus causes DNA damage and impairs gene expression and mRNA translation during infection of the placenta. Processes related to viral transcytosis, like endocytosis, autophagy and disruption of actin filament were also observed in CZS-infected placentas, which could lead to a higher virus infiltration. Unncontrolled maternal immune response as well as greater expression of cellular adhesion proteins in the decidua could lead to a disruption of tolerance during pregnancy and induction of neurological malformation of the neonates
2024-07-02 | PXD023777 | Pride
Project description:Zika virus (ZIKV) caused global concern due to Brazil's unexpected epidemic, and it was associated with congenital microcephaly and other gestational intercurrences. The study aimed to analyze the placenta morphometric changes of ZIKV-infected pregnant women (ZIKV group; n = 23) compared to placentas of HIV-infected (HIV group; n = 24) and healthy pregnant women (N-control group; n = 22). It also analyzed the relationship between the morphometric results and pathological alterations on conventional microscopy, gestational trimester of infection, and presence of the congenital Zika syndrome (CZS). There was a significant increase in area (p = 0.0172), as well as a higher number of knots (p = 0.0027), sprouts (p < 0.0001), and CD163 +Hofbauer cells (HCs) (p < 0.0001) in the ZIKV group compared to the N-control group, suggesting that villous dysmaturity and HCs hyperplasia could be associated with ZIKV infections. The HIV group had a higher area (p < 0.0001), perimeter (p = 0.0001), sprouts (p < 0.0001), and CD163 + HCs (p < 0.0001) compared to the N-control group, demonstrating that the morphometric abnormalities found in the ZIKV and HIV group are probably similar. However, when ZIKV and HIV groups are compared, it was observed a higher number of sprouts (p = 0.0066) and CD163+ HCs (p < 0.0001) in the first one, suggesting that placental ZIKV congenital changes could be more pronounced.
| S-EPMC8219962 | biostudies-literature
Project description:The IFITMs inhibit influenza A virus (IAV) replication in vitro and in vivo. Here, we establish that the antimycotic heptaen, amphotericin B (AmphoB), prevents IFITM3-mediated restriction of IAV, thereby increasing viral replication. Consistent with its neutralization of IFITM3, a clinical preparation of AmphoB, AmBisome, reduces the majority of interferon's protective effect against IAV in vitro. Mechanistic studies reveal that IFITM1 decreases host-membrane fluidity, suggesting both a possible mechanism for IFITM-mediated restriction and its negation by AmphoB. Notably, we reveal that mice treated with AmBisome succumbed to a normally mild IAV infection, similar to animals deficient in Ifitm3. Therefore, patients receiving antifungal therapy with clinical preparations of AmphoB may be functionally immunocompromised and thus more vulnerable to influenza, as well as other IFITM3-restricted viral infections.
| S-EPMC3898084 | biostudies-literature
Project description:The aim of this study was to study placental immune responses to ZIKV infection at the cell level. WT or MAVS-deficient placentas from mock- or ZIKV- infected pregnant WT or mutant mice were collected, and placentas from male fetuses selected to facilitate the identification of maternal and fetal clusters, and doublets. Two placentas from the same genotype and condition were pooled and processed for isolation of nuclei. Approximately 10,000 nuclei per sample were subjected to gel bead-in-emulsion (GEM) generation, reverse transcription, and construction of libraries for sequencing according to the protocol provided in the 3' gene expression v3.1 kit manual (10X Genomics). We obtained 98,661 nuclei with a median of 3,077 genes detected per nucleus after data processing and quality control. Seurat integrated analysis and graph-based clustering identified cell types in maternal and fetal compartments based on analysis of canonical cellular markers. We performed differential expression test using Wilcoxon test from Seurat to identify the changes in expression across conditions. The DSGs were then used to align to the Hallmark mouse pathway database Msigdbr (Version 7.5.1) with package fgsea (Version 1.26.0) and pathways that with P-adjusted value < 0.05 were chosen as the significantly enriched pathways. We found cell-type specific antiviral pathways driven by MAVS, and MAVS-independent induction of interferon-stimulated and antiviral genes in other cell types.
2024-06-11 | GSE269612 | GEO
Project description:Intrauterine growth restriction (IUGR) is a serious pathological complication associated with compromised fetal development during pregnancy. The aim of the study was to broaden knowledge about the transcriptomic complexity of the human placenta by identifying genes potentially involved in IUGR pathophysiology. RNA-Seq data were used to profile protein-coding genes, detect alternative splicing events (AS), single nucleotide variant (SNV) calling, and RNA editing sites prediction in IUGR-affected placental transcriptome. The applied methodology enabled detection of 37,501 transcriptionally active regions and the selection of 28 differentially-expressed genes (DEGs), among them 10 were upregulated and 18 downregulated in IUGR-affected placentas. Functional enrichment annotation indicated that most of the DEGs were implicated in the processes of inflammation and immune disorders related to IUGR and preeclampsia. Additionally, we revealed that some genes (S100A13, GPR126, CTRP1, and TFPI) involved in the alternation of splicing events were mainly implicated in angiogenic-related processes. Significant SNVs were overlapped with 6533 transcripts and assigned to 2386 coding sequence (CDS), 1528 introns, 345 5' untranslated region (UTR), 1260 3'UTR, 918 non-coding RNA (ncRNA), and 10 intergenic regions. Within CDS regions, 543 missense substitutions with functional effects were recognized. Two known mutations (rs4575, synonymous; rs3817, on the downstream region) were detected within the range of AS and DEG candidates: PA28? and PINLYP, respectively. Novel genes that are dysregulated in IUGR were detected in the current research. Investigating genes underlying the IUGR is crucial for identification of mechanisms regulating placental development during a complicated pregnancy.
| S-EPMC6471577 | biostudies-literature
Project description:Semiconducting polymer dots (Pdots) are small nanoparticles consisting primarily of fluorescent pi-conjugated polymers which show superior optical properties for biological imaging and biosensors. It is necessary to explore systematically the toxicity of Pdots on animals before extensive biomedical applications. The reproductive system is very sensitive to the external invasion and essential for species reproduction as well. In this work, we used the pregnant mice to investigate the reproductive toxicity of Pdots. The changes in body weight of each maternal mouse were recorded every two days. The main organs were collected and analyzed as soon as all the pregnant mice were sacrificed on the 15th embryonic day. Distributions of Pdots on maternal major organs and tissues were examined in frozen tissue sections. Hematoxylin and eosin (H&E) staining was performed to investigate the histopathological changes of maternal organs. The blood chemistry test was applied to study the effects of Pdots on organ functions. Female hormones were evaluated by immunoassays. The amniotic fluid was inspected for assessing their penetration ability of Pdots. Levels of placenta growth related factors were detected by RT-PCR to evaluate the function of placenta. These results showed that Pdots were mainly accumulated in liver and spleen, and no apparent impact was observed on maternal body weight and organs coefficients. Histopathological images also showed normal tissue morphology compared with the untreated group. The female hormones levels did not show significant difference among the three groups as well. Trace amount of Pdots could get into the amniotic fluid but did not change the placental functions and the early development of fetus. Our results demonstrated that Pdots have excellent biocompatibility and no reproductive toxicity under the dosages used in this work, which means that Pdots have great potential in preclinical applications in the future.
| S-EPMC5646735 | biostudies-literature
Project description:Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has adverse effects on gestation pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in angiogenesis, metabolic processes, anti-inflammatory, and reproductive development. However, the function of PPARγ in PFOS evoked disadvantageous effects on the placenta remain uncertain. Here, we explored the role of PPARγ in PFOS-induced placental toxicity. Cell viability, cell migration, angiogenesis, and mRNA expression were monitored by CCK-8 assay, wound healing assay, tube formation assay, and real-time PCR, respectively. Activation and overexpression of PPARγ were conducted by rosiglitazone or pcDNA-PPARγ, and inhibition and knockdown of PPARγ were performed by GW9662 or si-PPARγ. Results revealed that PFOS decreased cell growth, migration, angiogenesis, and increased inflammation in human HTR-8/SVneo and JEG-3 cells. Placenta diameter and fetal weight decreased in mice treated with PFOS (12.5 mg/kg). In addition, rosiglitazone or pcDNA-PPARγ rescued cell proliferation, migration, angiogenesis, and decreased inflammation induced by PFOS in HTR8/SVneo and JEG-3 cells. Furthermore, GW9662 or si-PPARγ exacerbated the inhibition of cell viability, migration, angiogenesis, and aggravated inflammation induced by PFOS in HTR-8/SVneo and JEG-3 cells. Meanwhile, the results of mRNA expression level were consistent with the cell representation. In conclusion, our findings revealed that PFOS induced placenta cell toxicity and functional damage through PPARγ pathway.
| S-EPMC8232579 | biostudies-literature