Maternal Transfer Research Articles

Fitness correlates of blubber oxidative stress and cellular defences in grey seals (Halichoerus grypus): support for the life-history-oxidative stress theory from an animal model of simultaneous lactation and fasting.

Life-history-oxidative stress theory predicts that elevated energy costs during reproduction reduce allocation to defences and increase cellular stress, with fitness consequences, particularly when resources are limited. As capital breeders, grey seals are a natural system in which to test this theory. We investigated oxidative damage (malondialdehyde (MDA) concentration) and cellular defences (relative mRNA abundance of heat shock proteins (Hsps) and redox enzymes (REs)) in blubber of wild female grey seals during the lactation fast (n = 17) and summer foraging (n = 13). Transcript abundance of Hsc70 increased, and Nox4, a pro-oxidant enzyme, decreased throughout lactation. Foraging females had higher mRNA abundance of some Hsps and lower RE transcript abundance and MDA concentrations, suggesting they experienced lower oxidative stress than lactating mothers, which diverted resources into pup rearing at the expense of blubber tissue damage. Lactation duration and maternal mass loss rate were both positively related to pup weaning mass. Pups whose mothers had higher blubber glutathione-S-transferase (GST) expression at early lactation gained mass more slowly. Higher glutathione peroxidase (GPx) and lower catalase (CAT) were associated with longer lactation but reduced maternal transfer efficiency and lower pup weaning mass. Cellular stress, and the ability to mount effective cellular defences, could proscribe lactation strategy in grey seal mothers and thus affect pup survival probability. These data support the life-history-oxidative stress hypothesis in a capitalbreeding mammal and suggest lactation is a period of heightened vulnerability to environmental factors that exacerbate cellular stress. Fitness consequences of stress may thus be accentuated during periods of rapid environmental change.

Glucoregulatory disruption in male mice offspring induced by maternal transfer of endocrine disrupting brominated flame retardants in DE-71.

Polybrominated diphenyl ethers (PBDEs) are commercially used flame retardants that bioaccumulate in human tissues, including breast milk. PBDEs produce endocrine and metabolic disruption in experimental animals and have been associated with diabetes and metabolic syndrome (MetS) in humans, however, their sex-specific diabetogenic effects are not completely understood. Our past works show glucolipid dysregulation resulting from perinatal exposure to the commercial penta-mixture of PBDEs, DE-71, in C57BL/6 female mice. As a comparison, in the current study, the effects of DE-71 on glucose homeostasis in male offspring was examined. C57BL/6N dams were exposed to DE-71 at 0.1 mg/kg/d (L-DE-71), 0.4 mg/kg/d (H-DE-71), or received corn oil vehicle (VEH/CON) for a total of 10 wks, including gestation and lactation and their male offspring were examined in adulthood. Compared to VEH/CON, DE-71 exposure produced hypoglycemia after a 11h fast (H-DE-71). An increased fast duration from 9 to 11h resulted in lower blood glucose in both DE-71 exposure groups. In vivo glucose challenge showed marked glucose intolerance (H-DE-71) and incomplete clearance (L- and H-DE-71). Moreover, L-DE-71-exposed mice showed altered glucose responses to exogenous insulin, including incomplete glucose clearance and/or utilization. In addition, L-DE-71 produced elevated levels of plasma glucagon and the incretin, active glucagon-like peptide-1 (7-36) amide (GLP-1) but no changes were detected in insulin. These alterations, which represent criteria used clinically to diagnose diabetes in humans, were accompanied with reduced hepatic glutamate dehydrogenase enzymatic activity, elevated adrenal epinephrine and decreased thermogenic brown adipose tissue (BAT) mass, indicating involvement of several organ system targets of PBDEs. Liver levels of several endocannabinoid species were not altered. Our findings demonstrate that chronic, low-level exposure to PBDEs in dams can dysregulate glucose homeostasis and glucoregulatory hormones in their male offspring. Previous findings using female siblings show altered glucose homeostasis that aligned with a contrasting diabetogenic phenotype, while their mothers displayed more subtle glucoregulatory alterations, suggesting that developing organisms are more susceptible to DE-71. We summarize the results of the current work, generated in males, considering previous findings in females. Collectively, these findings offer a comprehensive account of differential effects of environmentally relevant PBDEs on glucose homeostasis and glucoregulatory endocrine dysregulation of developmentally exposed male and female mice.

Pathogenesis and Prevention of Intraventricular Hemorrhage in Preterm Infants.

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

Development of an IgY-Based Treatment to Control Bovine Coronavirus Diarrhea in Dairy Calves

Bovine Coronavirus (BCoV) is a major pathogen associated with neonatal calf diarrhea. Standard practice dictates that to prevent BCoV diarrhea, dams should be immunized in the last stage of pregnancy to increase BCoV-specific antibody (Ab) titers in serum and colostrum. For the prevention to be effective, calves need to suck maternal colostrum within the first six to twelve hours of life before gut closure to ensure a good level of passive immunity. The high rate of maternal Ab transfer failure resulting from this process posed the need to develop alternative local passive immunity strategies to strengthen the prevention and treatment of BCoV diarrhea. Immunoglobulin Y technology represents a promising tool to address this gap. In this study, 200 laying hens were immunized with BCoV to obtain spray-dried egg powder enriched in specific IgY Abs to BCoV on a large production scale. To ensure batch-to-batch product consistency, a potency assay was statistically validated. With a sample size of 241, the BCoV-specific IgY ELISA showed a sensitivity and specificity of 97.7% and 98.2%, respectively. ELISA IgY Abs to BCoV correlated with virus-neutralizing Ab titers (Pearson correlation, R2 = 0.92, p < 0.001). Most importantly, a pilot efficacy study in newborn calves showed a significant delay and shorter duration of BCoV-associated diarrhea and shedding in IgY-treated colostrum-deprived calves. Calves were treated with milk supplemented with egg powder (final IgY Ab titer to BCoV ELISA = 512; VN = 32) for 14 days as a passive treatment before a challenge with BCoV and were compared to calves fed milk with no supplementation. This is the first study with proof of efficacy of a product based on egg powder manufactured at a scale that successfully prevents BCoV-associated neonatal calf diarrhea.

Sex-Specific Bioaccumulation, Maternal Transfer, and Tissue Distribution of Legacy and Emerging Per- and Polyfluoroalkyl Substances in Snakes (Enhydris chinensis) and the Impact of Pregnancy.

The effects of sex and pregnancy on the bioaccumulation and tissue distribution of legacy and emerging per- and polyfluoroalkyl substances (PFASs) in Chinese water snakes were investigated. The bioaccumulation factor of PFASs showed a positive correlation with their protein-water partition coefficients (log KPW), and steric hindrance effects were observed when the molecular volume was > 357 Å3. PFAS levels in females were significantly lower than those in males. The chemical composition of pregnant females was significantly different from that of non-pregnant females and males. The maternal transfer efficiencies of perfluorooctane sulfonic acid were higher than those of other PFASs, and a positive correlation between the maternal transfer potential and log KPW was observed for other PFASs. Tissues with high phospholipid content exhibited higher concentrations of ∑PFASs. Numerous physiological changes occurred in maternal organ systems during pregnancy, leading to the re-distribution of chemicals among different tissues. The change in tissue distribution of PFASs that are easily and not-so-easily maternally transferred was in the opposite direction. The extent of compound transfer from the liver to the egg determined tissue re-distribution during pregnancy.

Maternal effects drive intestinal development beginning in the embryonic period on the basis of maternal immune and microbial transfer in chickens

BackgroundNutrition drives immunity and health in animals, and maternal immunity benefits offspring. In our previous study, a nutritional intervention strategy was found to promote the immunity of hens, which subsequently improved immunity and growth in offspring chicks. Maternal effects clearly exist, but how are mothers’ immune advantages transferred to their offspring, and how do they benefit them?ResultsHere, we traced the beneficial effects back to the process of egg formation in the reproductive system, and we focused on the embryonic intestinal transcriptome and development, as well as on maternal microbial transfer in offspring. We found that maternal nutritional intervention benefits maternal immunity, egg hatching, and offspring growth. The results of protein and gene quantitative assays showed that the transfer of immune factors into egg whites and yolks depends on maternal levels. Histological observations indicated that the promotion of offspring intestinal development begins in the embryonic period. Microbiota analyses suggested that maternal microbes transfer to the embryonic gut from the magnum to the egg white. Transcriptome analyses revealed that offspring embryonic intestinal transcriptome shifts are related to development and immunity. Moreover, correlation analyses showed that the embryonic gut microbiota is correlated with the intestinal transcriptome and development.ConclusionsThis study suggests that maternal immunity positively influences offspring intestinal immunity establishment and intestinal development beginning in the embryonic period. Adaptive maternal effects might be accomplished via the transfer of relatively large amounts of maternal immune factors and by shaping of the reproductive system microbiota by strong maternal immunity. Moreover, reproductive system microbes may be useful resources for the promotion of animal health.53Hwa7T4Jvj9omDXNYBHSHVideo Graphical

Vaccination from the early second trimester onwards gives a robust SARS-CoV-2 antibody response throughout pregnancy and provides antibodies for the neonate

ObjectivesPreventive measures against COVID-19 are essential for pregnant women. Pregnant women are particularly vulnerable to emerging infectious pathogens due to alterations in their physiology. We aimed to determine the optimum timing of vaccination to protect pregnant women and their neonates from COVID-19. MethodsA prospective observational longitudinal cohort study in pregnant women who received COVID-19 vaccination. We collected blood samples to evaluate levels of antispike, receptor binding domain and nucleocapsid antibodies against SARS-CoV-2 before vaccination and 15 days after the first and second vaccination. We determined the neutralizing antibodies from mother-infant dyads in maternal and umbilical cord blood at birth. If available, immunoglobulin A was measured in human milk. ResultsWe included 178 pregnant women. Median antispike immunoglobulin G levels increased significantly from 1.8 to 5431 binding antibody units/ml and receptor binding domain from 6 to 4466 binding antibody units/ml. Virus neutralization showed similar results between different weeks of gestation at vaccination (P >0.3). ConclusionWe advise vaccination in the early second trimester of pregnancy for the optimum balance between the maternal antibody response and placental antibody transfer to the neonate.

Offspring of metal contaminated saltmarsh (Juncus acutus) exhibit tolerance to the essential metal Zn but not the nonessential metal Pb

Halophytes residing in metal-contaminated saltmarsh habitats may employ strategies to enhance fitness of the next generation. We aimed to test the hypothesis that Juncus acutus individuals inhabiting metal-contaminated locations would experience elevated tolerance of offspring to metals compared to plants residing in locations with no metal contamination history. J. acutus seeds (F1 generation) were collected from F0 parent plants residing at eight locations of a contemporary sediment metal gradient (contaminated to uncontaminated) across the coast of NSW, Australia (Hunter river, Lake Macquarie and Georges River). Seeds were exposed in the laboratory to incremental Zn (0.0–1.6 mM) and Pb (0.0–0.50 mM) for nine (9) days, and % germination, germination rate, root elongation and vigour index were assessed for the determination of tolerance. Greater root accumulation (BCF = 1.01) of Zn and subsequent translocation to aerial parts (culm BCF = 0.58 and capsule BCF = 0.85) were exhibited in parents plants, whereas Pb was excluded from roots (BCF = 0.60) and very little translocation to aerial portions of the plant was observed (culm BCF = 0.02 and capsule BCF = 0.05). F1 offspring exhibited tolerance to Zn with EC50 (% germination) significantly correlated with their parents' culm (R2 = 0.93, p = 0.00) and capsule (R2 = 0.57; p = 0.03) Zn. No correlations were observed between offspring Pb tolerance and Pb in parents’ plant tissues. Enhanced tolerance to the essential metal Zn may be because Zn is very mobile in the parent plant and seeds experience greater Zn load as a significant portion of sediment Zn reaches capsules (85%). Thus, Zn tolerance in J. acutus seeds is likely attributable to acclimation via maternal transfer of Zn; however, further manipulative experiments are required to disentangle potential acclimation, adaptation or epigenetic effects in explaining the tolerance observed.

Maternal antibiotic treatment during pregnancy attenuates the transport and absorption of maternal antibody IgG through TLR4 and TLR2 receptor.

Maternal antibody IgG, the main antibody in colostrum, plays an important role in neonates protection. Commensal microbiota is closely related to host antibody repertoire. However, there are few reports on how maternal gut microbiota affects maternal antibody IgG transfer. In the present study, we investigated the effects of altering the gut microbiota (treated with antibiotics during pregnancy) on maternal IgG transportation and offspring absorption and explored its underlying mechanisms. Results showed that antibiotic treatment during pregnancy significantly decreased maternal cecal microbial richness (Chao1 and Obesrved species) and diversity (Shannon and Simpson). Plasma metabolome enriched significant changes in the process of bile acid secretion pathway, and the concentration of deoxycholic acid, a secondary metabolite of microorganisms was lowered. Flow cytometry analysis indicated that antibiotic treatment promoted the number of B cells and abated the number of T, DC and M1 cells in intestinal lamina propria of dams. Surprisingly, the serum IgG level in antibiotic treated dams was significantly increased, while IgG contents in colostrum was decreased. Moreover, pregnancy antibiotic treatment in dams was reduced the expression of FcRn, TLR4 and TLR2 in breast of dams and in duodenum and jejunum of neonates. Furthermore, TLR4-/- and TLR2-/- knock-out mice showed a lower FcRn expression in breast of dams and in duodenum and jejunum of neonates. These findings suggest that maternal intestine bacteria may affect the maternal IgG transfer through regulating the breast TLR4 and TLR2 of dams.

First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility

To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated invitro fertilization (IVF) failures for the treatment of idiopathic infertility. A prospective pilot study. IVF center. Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, invitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

Maternal transfer of florfenicol impacts development and disrupts metabolic pathways in F1 offspring zebrafish by destroying mitochondria

Maternal exposure to antibiotics existing in the environment is a predisposing factor for developmental malformation with metabolic disorders in offspring. In this study, female zebrafish (3 months) were exposed to 0.05 mg/L and 0.5 mg/L florfenicol (FF) for 28 days. After pairing and spawning with healthy male fish, F1 embryos were collected and developed to 5 d post-fertilization (dpf) in clear water. And the adverse effects on the F1 generation were examined thoroughly. The fecundity of F0 female fish and the hatchability, mortality, and body length of F1 larvae significantly decreased in the treatment group. Meanwhile, multi-malformation types were found in the exposure group, including delayed yolk sac absorption, lack of swim bladder, and spinal curvature. Metabolomic and transcriptomic results revealed alterations in metabolism with dysregulation in tricarboxylase acid cycle, amino acid metabolism, and disordered lipid metabolism with elevated levels of glycerophospholipid and sphingolipid. Accompanying these metabolic derangements, decreased levels of ATP and disordered oxidative-redox state were observed. These results were consistent with the damaged mitochondrial membrane potential and respiratory chain function, suggesting that the developmental toxicity and perturbed metabolic signaling in the F1 generation were related to the mitochondrial injury after exposing F0 female zebrafish to FF. Our findings highlighted the potential toxicity of FF to offspring generations even though they were not directly exposed to environmental contaminants.

Antibody-based protection against respiratory syncytial virus in mice and their offspring through vectored immunoprophylaxis.

Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, with potential lower respiratory tract infections, which can be particularly problematic in infants and the elderly. There are no approved vaccines for RSV. The current standard of care for high-risk individuals is monthly administration of palivizumab, a humanized murine monoclonal antibody (mAb) targeting the RSV fusion protein. Adeno-associated virus (AAV)-mediated expression of mAbs has previously led to sustained expression of therapeutic concentrations of mAbs in several animal models, representing an alternative to repetitive passive administration. Intramuscular (IM) administration of AAV6.2FF expressing RSV antibodies, palivizumab or hRSV90, resulted in high concentrations of human (h)IgG1 mAbs in the serum and at various mucosal surfaces, while intranasal administration limited hIgG expression to the respiratory tract. IM administration of AAV6.2FF-hRSV90 or AAV6.2FF-palivizumab in a murine model provided sterilizing immunity against challenge with RSV A2. Evidence of maternal passive transfer of vectorized hRSV90 was detected in both murine and ovine models, with circulating mAbs providing sterilizing immunity in mouse progeny. Finally, addition of a "kill switch" comprised of LoxP sites flanking the mAb genes resulted in diminished serum hIgG after AAV-DJ-mediated delivery of Cre recombinase to the same muscle group that was originally transduced with the AAV-mAb vector. The ability of this AAV-mAb system to mediate robust, sustained mAb expression for maternal transfer to progeny in murine and ovine models emphasizes the potential of this platform for use as an alternative prophylactic vaccine for protection against neonatal infections, particularly in high-risk infants.

Maternal Nutritional Factors, Fetal Macrosomia and Increased Risk of Childhood Obesity: Effects of Excess Placental Transfer of Maternal Glucose and Fatty Acids

Background: Maternal nutritional factors play a significant role in maternal glucose and fatty acid transfer across the placenta and contribute to further enhancing fetal growth and also increasing the risk of fetal macrosomia. Objective: This review aims to provide the effects of placental transfer of maternal fatty acids and glucose on fetal macrosomia, and also highlights the maternal nutritional interventions to prevent fetal adiposity. Method: All abstracts and full-text articles have been examined and the most relevant articles have been included in this review. Results: Maternal obesity, maternal over-nutrition, and gestational diabetes can permanently influence the risk of macrosomia via the effects of the placental transfer of maternal fatty acids and glucose on the fetus. These conditions are associated with unfavorable maternal environments that lead to fetal growth acceleration by adverse fetal programming outcomes and increased risk of childhood obesity. As a result, pregnancy should be viewed as a window of opportunity for the development of maternal nutritional therapies that improve maternal glucose and lipid metabolism, potentially reducing macrosomia and juvenile obesity. Conclusion: Evidence-based techniques for managing maternal glucose and fatty acid transfer to the fetus include maintaining maternal pre-pregnancy body mass index (BMI), acceptable weight gain throughout pregnancy, and maternal nutritional interventions during pregnancy. Healthy dietary patterns (such as the Mediterranean diet) and/or dietary consumption of certain nutrients (such as omega-3 fatty acids) are among the suggestions for fetal macrosomia prevention.

Use of Nitroglycerine Patch in the Management of Preterm Labor

Background: Preterm birth is the delivery of the baby before 37 completed weeks of pregnancy. The goal of tocolytic therapy is to reduce neonatal mortality and morbidity by delaying birth, allowing for corticosteroid administration and maternal transfer to the tertiary care center. This study was conducted to observe the tocolytic efficacy of GTN transdermal patches in preterm labor between 28 – 36 weeks of pregnancy. Methods: This cross-sectional study was done in Obstetrics &amp; Gynecology Department at Mufti Mehmood Memorial Hospital, Dera Ismail Khan, from July 2017 to December 2017. Non-probability consecutive samplings of 186 pregnant women with preterm labor were included in the study. Detailed history and examination, routine investigations and ultrasound were performed to confirm viability, gestational age and exclusion of multiple pregnancies, lethal fetal malformation and intrauterine death. Effectiveness of the GTN patch was considered successful if the cessation of uterine contraction occurred within 24 hours of the application of the GTN patch and persisted for 48 hours to achieve the effect of steroids. Results: Tocolytic efficacy of GTN transdermal patch in preterm labor between 28 to 36 weeks of pregnancy was 88.71%. Regarding the parity of the women, 75.8% of women had multipara (parity 2 to 5) and 24.2% had primipara. The average gestational age was 33.15±2.28 weeks. . Two to three uterine contractions per 10 minutes were observed in 75.8% of women while four uterine contractions per 10 minutes were observed in 24.19% of cases. 2cm cervical dilatation was observed in 82 women (44.09%) and 3cm was 75 women (40.32%). Practical implication: The incidence of preterm delivery can be minimized using GTN patch to reduce the uterine contractions and increase the fetal viability inside the womb. Conclusion: There is no better incubator than a mother's womb. The GTN patch appears to be a safe, non-invasive method of suppressing uterine contractions in pre-term labor and also a simple, quicker and cost-effective tocolytic agent. Keywords: Pre-term labor; Tocolytic; Transdermal patch; Uterine contractions.

Growth inhibition of offspring larvae caused by the maternal transfer effects of tetrabromobisphenol A in zebrafish

Tetrabromobisphenol A (TBBPA) is an industrial chemical and the most widely used brominated flame retardant, and has raised environmental health concerns. However, the maternal transfer toxicity of TBBPA is less studied in fish despite its frequency in the water environment, and limited evidence exists to confirm the major contributing factors. In this study, we performed a 28-d experiment on female and male zebrafish exposed to TBBPA (0, 5, 50, and 500 μg/L), and shortened body length of offspring larvae was observed at the maximum exposure concentration. By cross-mating control and exposed zebrafish (male or female), our results showed that the observed growth inhibition in the progeny was attributed to the maternal transfer effect. Although 28-d exposure resulted in the existence of TBBPA in ovaries and ova, the maternal transfer of TBBPA was not responsible for the shortened body length of offspring larvae, as evidenced through TBBPA embryo microinjection. Moreover, proteomic analyses in ova indicated that the abundance of apolipoproteins (apoa1, apoa1b, apoa2, apoa4b, and apoc1) was significantly downregulated in the ova, which may be partially responsible for the shortened body length of offspring larvae. Interestingly, these proteins did not differentially express in the ovaries. Therefore, our results demonstrate that TBBPA exposure disturbed maternal protein transfer from the ovaries to the ova, providing novel insights into the underlying maternal transfer effects.

Occurrence and tissue-specific partitioning of alternative brominated flame retardants in northwest Atlantic harbor seal pups (Phoca vitulina vitulina)

Brominated flame retardants such as polybrominated diphenyl ethers (PBDEs) have been used for decades until evidence of negative health effects led to bans in many countries. PBDEs have since been replaced by alternative legacy compounds or newly developed chemicals. In this study, eight alternative brominated flame retardants were analyzed in blubber and liver of harbor seal pups (≤6 months) from the Northwest Atlantic collected during 2001–2010 to elucidate concentrations, patterns, contamination trends, potential maternal transfer, and tissue partitioning. All compounds were detected in liver and blubber tissues with hexabromocyclododecane (HBCD) isomers and 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) predominating. Overall, α-HBCD was the dominant HBCD isomer in both tissues although the concentrations of γ-HBCD exceeded those of α-HBCD in seven pups, indicating their mothers may have had alternative dietary patterns or recent exposure to the commercial mixture. Although it was detected in less than half of the samples, to our knowledge, this is the first study to report tetrabromobisphenol A (TBBPA) concentrations in multiple tissues of a top marine predator. For the brominated components of Firemaster® flame retardants, TBB concentrations exceeded bis-(2-ethylhexyl)-tetrabromophthalate (TBPH). This pattern may result from recent exposure to commercial mixtures in which TBB exceeds TBPH 4:1 or from differences in perinatal or lactational transfer efficiency of the two compounds. Between the two tissues, lipid-normalized β-HBCD, γ-HBCD, TBB and decabromodiphenyl ethane (DBDPE) concentrations were significantly higher in liver than blubber. This indicates that the bioaccumulation of these chemicals is not simply related to lipid dynamics but may be linked to blood proteins. This study demonstrates that harbor seal pups from this region are contaminated with alternative flame retardants passed to them via placental or lactational transfer. Given the evidence for negative health effects of these chemicals, this contamination adds additional pressure on the first year survival of these young, developing animals.

Major, minor and trace element concentrations in the muscle and liver of a pregnant female Pacific sharpnose shark (Rhizoprionodon longurio) and its embryos

The Pacific sharpnose shark Rhizoprionodon longurio is an abundant shark consumed by human population in Mexico. This study aimed to determine and compare the concentrations of thirteen essential elements (K, S, P, Na, Ca, Mg, Fe, Zn, Se, Cu, Mn, Cr and Co) and eleven non-essential elements (As, Sr, Cd, V, Li, U, Tl, Ag, Sn, Sb and Pb) in the muscle and liver of a pregnant female, fished near the copper mine of Santa Rosalía, and their respective embryos. Major, minor and trace (essential and non-essential) elements were transferred during gestation to embryos. All major elements analyzed had significantly higher concentrations in embryos liver than the pregnant female, except for magnesium. Higher concentrations in embryo tissues than the pregnant female tissues were found for the non-essential trace elements of strontium, lithium, thallium and silver, which indicate an easy maternal transfer of these non-essential elements.

Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies: A retrospective study

IntroductionPreeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies. MethodsIn this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies. ResultsFocusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy. DiscussionOur data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.

The Immunogenicity of a VLP-based Malaria Vaccine Targeting CSP in Pregnant and Neonatal Mice.

Maternal antibodies are passively transferred to the fetus via the placenta during gestation and can play an important role in protecting the newborn from infection. For example, in malaria-endemic regions, maternal antibodies likely provide substantial protection against Plasmodium falciparum malaria in the first 6 months of life. However, circulating maternal antibodies can also interfere with vaccine efficacy. Here, we used a mouse maternal transfer model to evaluate whether maternal antibodies interfere with the responsiveness to a virus-like particle (VLP)-based vaccine targeting the CIS43 epitope of the malaria circumsporozoite protein (CSP). We found immunized dams passively transfer to pups high levels of anti-CSP IgG antibodies that steadily decline as the animals age. We also found that the neonatal offspring of immunized mice do not respond to de novo immunization with the CIS43-targeted VLP vaccine until maternal antibody titers decline below an inhibitory threshold. These findings may have important implications for delineating the delicate balance between protection conferred by maternal antibodies and the offspring's ability to respond to immunization.

Intermediate Levels of Pre-Existing Protective Antibody Allow Priming of Protective T Cell Immunity against Influenza.

Overcoming interfering impacts of pre-existing immunity to generate universally protective influenza A virus (IAV)-specific T cell immunity through vaccination is a high priority. In this study, we passively transfer varied amounts of H1N1-IAV-specific immune serum before H1N1-IAV infection to determine how different levels of pre-existing Ab influence the generation and protective potential of heterosubtypic T cell responses in a murine model. Surprisingly, IAV nucleoprotein-specific CD4 and CD8 T cell responses are readily detected in infected recipients of IAV-specific immune serum regardless of the amount transferred. When compared with responses in control groups and recipients of low and intermediate levels of convalescent serum, nucleoprotein-specific T cell responses in recipients of high levels of IAV-specific serum, which prevent overt weight loss and reduce peak viral titers in the lungs, are, however, markedly reduced. Although detectable at priming, this response recalls poorly and is unable to mediate protection against a lethal heterotypic (H3N2) virus challenge at later memory time points. A similar failure to generate protective heterosubtypic T cell immunity during IAV priming is seen in offspring of IAV-primed mothers that naturally receive high titers of IAV-specific Ab through maternal transfer. Our findings support that priming of protective heterosubtypic T cell responses can occur in the presence of intermediate levels of pre-existing Ab. These results have high relevance to vaccine approaches aiming to incorporate and evaluate cellular and humoral immunity towards IAV and other viral pathogens against which T cells can protect against variants escaping Ab-mediated protection.