Exposure Of Offspring Research Articles

Combining information from parental and personal experiences: Simple processes generate diverse outcomes.

Experiences of parents and/or offspring are often assumed to affect the development of trait values in offspring because they provide information about the external environment. However, it is currently unclear how information from parental and offspring experiences might jointly affect the information-states that provide the foundation for the offspring phenotypes observed in empirical studies of developmental plasticity in response to environmental cues. We analyze Bayesian models designed to mimic fully-factorial experimental studies of trans and within- generational plasticity (TWP), in which parents, offspring, both or neither are exposed to cues from predators, to determine how different durations of cue exposure for parents and offspring, the devaluation of information from parents or the degradation of information from parents would affect offspring estimates of environmental states related to risk of predation at the end of such experiments. We show that the effects of different cue durations, the devaluation of information from parents, and the degradation of information from parents on offspring estimates are all expected to vary as a function of interactions with two other key components of information-based models of TWP: parental priors and the relative cue reliability in the different treatments. Our results suggest empiricists should expect to observe considerable variation in the patterns observed in experimental studies of TWP based on simple principles of information-updating, without needing to invoke additional assumptions about costs, tradeoffs, development constraints, the fitness consequences of different trait values, or other factors.

The relationship between maternal perfluoroalkylated substances exposure and low birth weight of offspring: a systematic review and meta-analysis.

Some studies have shown that maternal perfluoroalkylated substances (PFAS) exposure may be associated with low birth weight (LBW) of offspring. We conducted a meta-analysis to assess the association between maternal PFASs exposure and LBW in offspring. The researchers searched PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase to find all the articles before October 2020. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Finally, six articles were included for meta-analysis. Our meta-analysis showed no significant correlation between maternal perfluorooctanoic acid (PFOA) exposure and LBW of offspring: odds ratio (OR) = 0.90, 95% confidence interval (95% CI) = 0.80-1.01, with low heterogeneity (I2 = 18.4%, P = 0.289); there was a significant positive correlation between maternal perfluorooctane sulfonate (PFOS) exposure and LBW of offspring (OR = 1.32, 95% CI = 1.09-1.55) with no heterogeneity (I2 = 0.00%, P = 0.570). The grouping analysis of PFOS showed was a significant positive correlation between maternal PFOS exposure and LBW of offspring in American (OR = 1.44, 95% CI = 1.15-1.72). This study provided a systematic review and meta-analysis evidence for the relationship between maternal PFASs exposure and LBW of offspring through a small number of studies. Researchers should conduct further studies between different regions.

Abstract LB229: Environmentally-induced epigeneticinheritance of cancer: Paternal exposure to pesticides induces intergenerational programming of breast cancer predisposition via sperm small RNAs

Abstract Background: DNA sequence accounts for the majority of disease heritability, including cancer. However, it is becoming clear that environmentally-induced epigenetic inheritance of disease can also occur. Epidemiological studies have shown that parental exposure to the pesticide DDT and other environmental toxicants is associated with increased tumor development, particularly breast cancer, in offspring. Here, we tested whether paternal exposure to DDT could lead to intergenerational increase in breast cancer development using a mouse model. We also investigated the mechanisms of intergenerational transmission.Methods: Male mice (c57bl/6) were exposed to DDT or to a control-vehicle (CO) solution and used for sperm collection or mating with unexposed females to produce the DDT or CO daughters. In another experiment, normal mouse embryos (zygote stage) were injected with purified sperm RNAs or synthetic miRNA-10b and implanted into surrogate mothers to produce RNA-injected offspring. DDT daughters or RNA injected females were used to study breast cancer development (carcinogen-induced or orthotopic models) and metabolic parameters. Paternal sperm was used for RNA-seq analysis and miRNA expression levels. Results: Pre-conception paternal DDT exposure altered the sperm small non-coding RNA load, with an increase in miRNAs and a specific surge in miRNA-10b levels. DDT offspring weighed less at birth and at weaning, but became overweight and showed metabolic dysfunction in adulthood compared to CO. DDT daughters also showed increased mammary tumorigenesis, developing more aggressive tumors that grew faster than in CO. This tumor phenotype was linked to suppression of the AMPK energy sensing pathway and mTOR activation in mammary tissues. Remarkably, embryonic injection of purified DDT sperm RNA or synthetic miRNA-10b recapitulated the mammary gland and tumor phenotypes observed in DDT daughters. Conclusions: To our knowledge, this is the first report of an association between paternal DDT exposure and breast cancer in offspring. Paternal DDT-induced programming of breast cancer development in daughters is mechanistically linked to sperm RNAs and, more specifically, miRNA-10b. The impact of DDT and other endocrine disrupting chemicals on sperm and programming of breast and other cancers in offspring needs to be evaluated in humans. Citation Format: Raquel Santana Da Cruz, Hong Cao, Camile C. Fontelles, Apsra Nasir, Alexandra K. Gonsiewski, M. Idalia Cruz, Lu Jin, Sonia de Assis. Environmentally-induced epigeneticinheritance of cancer: Paternal exposure to pesticides induces intergenerational programming of breast cancer predisposition via sperm small RNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB229.

PFOA Exposure Prior to Hepatocyte Differentiation Leads to Gene Expression Changes Implicated in Non-Alcoholic Fatty Liver Disease

Background: Perfluorooctanoic acid (PFOA), is a persistent fluorinated compound with oil and water repelling properties found in cookware, food packaging and municipal water systems. Adult animals exposed to PFOA develop hepatomegaly, fatty liver, peroxisome proliferation, and immunotoxicity. Rodents exposed to PFCs in utero have altered hepatic lipid metabolism, increased hepatic de novo lipogenesis and susceptibility to non-alcoholic fatty liver disease (NAFLD), but underlying molecular mechanisms remain unknown. With increasing rates of obesity, diabetes, and NAFLD it is critical to examine the mechanisms by which in utero exposure to PFOA contributes to the development of metabolic syndrome in offspring. Objective: To determine mechanism by which PFOA alters gene expression in undifferentiated hepatic progenitor cells. Design/methods: HepaRG cells, a human derived hepatocyte progenitor cell line, was treated with 0.5uM PFOA or vehicle for 48 hours followed by differentiation into hepatocytes. Total RNA was extracted using the RNeasy (Qiagen) [total RNA A260/280>2 and RNA integrity number >7 (Agilent Bioanalyzer)] to generate libraries with the Illumina TruSeq stranded total RNA kit. RNA-Seq was performed using 85 bp single-end read sequencing to generate >20 million reads per sample. RNAseq data was aligned to hg38 using STAR v2.6.1a and then quantified with featureCounts v1.6.2. DESeq2 identified differentially expressed genes via FDR (false discovery rate) after Bonferroni correction. Differentially expressed gene lists were used for Ingenuity Pathway Analysis (IPA) to identify pathways of biological significance.Results: PFOA treatment resulted in increased expression of transcription factors EGR1 (early growth response protein 1), NR4A1 (nuclear receptor Nur77), EGR2 (early growth response protein 2), KLF10 (Krueppel-like factor 10) and FOSL1 (Fos-related antigen 1), key genes linked to impaired hepatic insulin signaling, hepatic lipid metabolism, steatosis and fibrosis (fold change > 1.5; q <0.05). IPA identified enrichment of canonical pathways with biological relevance including hepatic fibrosis signaling, stellate cell activation, VDR/RXR/TR activation, and Type 2 diabetes mellitus signaling (p<0.01). Conclusion: Hepatocyte progenitor cells exposed to low dose PFOA for 48 hours prior to differentiation results in changes in expression of key metabolic genes linked to the development of NAFLD and enrichment of biologically relevant pathways associated with hepatic fibrosis and hepatocellular carcinoma. These results suggest that PFOA exposure in utero may have lasting effects on hepatic glucose and lipid metabolism after differentiation. Further studies are needed to characterize the longstanding metabolic effects of in utero PFOA exposure in offspring and the mechanisms driving the persistence of these changes.

Association between prenatal air pollution exposure and risk of hypospadias in offspring: a systematic review and meta-analysis of observational studies.

Background: The findings of associations between prenatal air pollution exposure and hypospadias risk in offspring are inconsistent. No systematic review or meta-analysis has yet summarized the present knowledge on the aforementioned topic.Methods: Relevant manuscripts were identified by searching PubMed and Web of Science databases through January 31, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) in meta-analyses were estimated based on a random effects model. Publication bias was evaluated by funnel plots, Begg’s test, and Egger’s test.Results: The search identified 3,032 relevant studies. Sixteen studies cumulatively involving 21,701 hypospadias cases and 1,465,364 participants were included. All of these studies were classified as having a low risk of bias. We classified pollutants as nitrogen oxides, particulate matter (PM), ozone, and other exposures. The exposure window to pollutants varied from three months before conception to seven days after delivery. In the meta-analyses, only PM2.5 exposure in the first trimester was related to increased risk of hypospadias (per 10 μg/m3 OR = 1.34; 95% CI: 1.06–1.68).Conclusion: We found evidence for an effect of PM2.5 exposure on hypospadias risk. Improvements in the areas of study design, exposure assessment, and specific exposure window are needed to advance this field.

Prenatal exposure to acetaminophen increases the risk of atopic dermatitis in children: A nationwide nested case-control study in Taiwan.

Acetaminophen (APAP) has been associated with the development of atopic diseases. However, little is known about the relationship between prenatal APAP exposure and atopic dermatitis (AD) in offspring. To investigate the association between prenatal APAP exposure and AD risk in offspring. In this study, 2029 study pairs (AD-affected children and their mothers) and 5,058 control pairs were identified between 1998 and 2008 from the Taiwan Longitudinal Health Insurance Database. Maternal APAP exposure during pregnancy was assessed. After adjustment for potential confounders, there was a significant association between risk of offspring AD and exposure to acetaminophen in the first trimester (OR 1.16; 95% CI 1.05-1.28), the second trimester (OR 1.14; 95% CI 1.03-1.27), both first and second trimesters (OR 1.30; 95% CI 1.13-1.51), both first and third trimester (OR 1.20; 95% CI 1.04-1.39), any trimester (OR 1.12; 95% CI 1.00-1.26), and all three trimesters (OR 1.32; 95% CI 1.08-1.62) in a dose-response manner. Prenatal exposure to acetaminophen was associated with an increased incidence of offspring AD.

Pre- and postnatal maternal smoking and offspring smoking trajectories: Evidence from a 20-year birth cohort

Maternal smoking is associated with increased risk of smoking in the offspring. However, it remains unclear whether this association depends on the timing of exposure to maternal smoking. We investigated the association between prenatal and/or postnatal maternal smoking and offspring smoking during adolescence. Participants (N = 1661) were from the Québec Longitudinal Study of Child Development cohort. We identified longitudinal trajectories of maternal smoking from before pregnancy to child age 12 years using group-based trajectory modeling (GBTM). Adolescent (12–19 years) smoking trajectories were also identified using GBTM. Associations between maternal smoking and offspring smoking trajectories were estimated using multinomial logistic regressions. We used propensity score inverse probability weighting (IPW) to account for the differential distribution of maternal and familial characteristics across exposure groups. We identified four distinct groups for maternal smoking: no (66.1%), decreasing (5.6%), increasing (9.5%) and persistent (18.8%) smoking, and three adolescent smoking trajectories: abstinent, early-onset (before age 15) and late-onset (after age 15). In IPW-adjusted models, youth with mothers with decreasing, increasing and persistent smoking had higher risk of being early-onset smokers compared with youth with mothers in the non-smoking group. We also found that only youth whose mothers were persistent smokers had an increased risk of late-onset smoking. Regardless of timing, offspring exposure to maternal smoking is associated with increased risk of smoking during adolescence. More research is needed on how to create effective smoking cessation campaigns that span preconception, prenatal, and postnatal periods to help prevent intergenerational transmission of smoking behaviors.

Maternal obesity interrupts the coordination of the unfolded protein response and heat shock response in the postnatal developing hypothalamus of male offspring in mice

Maternal obesity malprograms offspring obesity and associated metabolic disorder. As a common phenomenon in obesity, endoplasmic reticulum (ER) stress also presents early prior to the development. Here, we investigate metabolic effect of early activated hypothalamic ER stress in offspring exposed to maternal obesogenic environment and the underlying mechanism in ICR mice model. We found higher body weight, hyperphagia and defective hypothalamic feeding-circuit in the offspring born to obese dams, with hypothalamic ER stress, and even more comprehensive cell proteotoxic stress were induced during the early postnatal period. However, neonatal inhibition of hypothalamic ER stress worsened the metabolic end. We believe that the uncoordinated interaction between the unfolded protein response and the heat shock response, regulated by heat shock protein 70, might be responsible for the malformed hypothalamic feeding circuit of the offspring exposure to maternal obesogenic conditions and were linked with deleterious metabolism in adulthood, especially when exposure to high-energy conditions.

Parental PM2 .5 exposure changes Th17/Treg cells in offspring, is associated with the elevation of blood pressure.

Epidemiological evidences have indicated that fine particulate matter (PM2.5 ) exposure is associated with the occurrence and development of hypertension. The present study aims to explore the effects of parental PM2.5 exposure on blood pressure in offspring and elucidate the potential mechanism. The parental male and female C57BL/6 mice were exposed to concentrated PM2.5 or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) for 16 weeks. At week 12, the mice were assigned to breed offspring. The male offspring mice were further exposed to PM2.5 or FA as above method. During the parental exposure, the average PM2.5 concentration was 133.7 ± 53.32 μg/m3 in PM chamber, whereas the average concentration in FA chamber was 9.4 ± 0.23 μg/m3 . Similarly, during the offspring exposure, the average concentration in PM and FA chamber were 100.76 ± 26.97 μg/m3 and 9.15 ± 0.15 μg/m3 , respectively. The PM2.5 -exposed offspring mice displayed the elevation of blood pressure, the increase of angiotensin II (Ang II), the decrease of angiotensin converting enzyme 2 (ACE2) and Ang (1-7) in serum when compared with the FA-exposed offspring mice. The similar results displayed in the proteins expression of ACE2, AT1R, and Ang (1-7) in vessel and kidney. More importantly, parental PM exposure further induced the increase in serous Ang II and the protein expression of AT1R in vessel, but decrease in ACE2 and Ang (1-7). The serous Ang II was positively associated with splenic T helper type 17 (Th17) cell population and serous IL (interleukin)-17A, but negatively associated with T regular (Treg) cell population and serous IL-10. The results suggested that parental air pollution exposure might induce the elevation of offspring blood pressure via mediate Th17- and Treg-related immune microenvironment.

Metabolomics analysis of maternal serum exposed to high air pollution during pregnancy and risk of autism spectrum disorder in offspring

BackgroundPreviously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring. ObjectivesTo identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD. MethodsWe obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mothers with offspring who later developed ASD and 98 control mothers. Partial least squares discriminant analysis (PLS-DA) was employed to select metabolic features associated with air pollution exposure or autism risk in offspring. We also conducted extensive pathway enrichment analysis to elucidate potential ASD-related changes in the metabolome of pregnant women. ResultsWe extracted 4022 and 4945 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for potential confounders, we identified 167 and 222 discriminative features (HILIC and C18, respectively). Pathway enrichment analysis to discriminate metabolic features associated with ASD risk indicated various metabolic pathway perturbations linked to the tricarboxylic acid (TCA) cycle and mitochondrial function, including carnitine shuttle, amino acid metabolism, bile acid metabolism, and vitamin A metabolism. ConclusionUsing high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.

Prenatal dexamethasone exposure induces nonalcoholic fatty liver disease in male rat offspring via the miR-122/YY1/ACE2-MAS1 pathway

Epidemiological studies have shown that nonalcoholic fatty liver disease (NAFLD) has an intrauterine developmental origin. We aimed to demonstrate that NAFLD is caused by prenatal dexamethasone exposure (PDE) in adult male rat offspring and to investigate the intrauterine programming mechanism. Liver samples were obtained on gestational day (GD) 21 and postnatal week (PW) 28. The effects and epigenetic mechanism of dexamethasone were studied with bone marrow mesenchymal stem cells (BMSCs) hepatoid differentiated cells and other cell models. In the PDE group, lipid accumulation increased, triglyceride synthesis-related gene expression increased, and oxidation-related gene expression decreased in livers of adult male rat offspring. In utero, hepatic triglyceride synthesis increased and oxidative function decreased in PDE fetal male rats. Moreover, low hepatic miR-122 expression, high Yin Yang-1 (YY1) expression and angiotensin-converting enzyme 2 (ACE2)-Mas receptor (MAS1) signaling pathway inhibition were observed before and after birth. At the cellular level, dexamethasone (100–2500 nM) elevated the intracellular triglyceride content, increased triglyceride synthesis-related gene expression and decreased oxidation-related gene expression. Dexamethasone treatment also decreased miR-122 expression, increased YY1 expression and inhibited the ACE2-MAS1 signaling pathway. Interference or overexpression of glucocorticoid receptor (GR), miR-122, YY1 and ACE2 could reverse the changes in downstream gene expression. In summary, PDE could induce NAFLD in adult male rat offspring. The programming mechanism included inhibition of miR-122 expression after GR activation, and dexamethasone increased hepatocyte YY1 expression; these effects resulted in ACE2-MAS1 signaling pathway inhibition, which led to increased hepatic triglyceride synthesis and decreased oxidative function. The increased triglyceride synthesis and decreased oxidative function of hepatocytes caused by low miR-122 expression due to dexamethasone could continue postnatally, eventually leading to NAFLD in adult rat offspring.

Prenatal exposure to methamphetamine in rats induces endothelial dysfunction in male but not female adult offspring.

In utero exposure to methamphetamine results in significant developmental, neurological, and behavioral deficits in offspring. However, very little is known about the cardiovascular effects of prenatal methamphetamine exposure in adult offspring. We hypothesized that prenatal methamphetamine exposure causes adverse cardiovascular effects in adult offspring. The aims of this study were to test the effects of prenatal methamphetamine exposure on blood pressure and endothelial function in male and female adult rat offspring. Pregnant rats were injected with methamphetamine (5mgkg-1day-1) or saline throughout pregnancy. Conscious blood pressure and vascular function in mesenteric-resistance arteries were measured in male and female adult offspring using tail cuff and myography, respectively (beginning at 8weeks old). In adult male offspring, but not in adult female offspring, endothelium-dependent relaxation to acetylcholine was impaired in methamphetamine-exposed compared to saline-exposed rats. Vascular relaxation to diethylamine NONOate diethylammonium salt was not impacted by gender or prenatal exposure. Prenatal methamphetamine exposure had no effect on systolic blood pressure in offspring of either gender. These data suggest that prenatal methamphetamine exposure adversely affects endothelial function in a sex-dependent manner. Clinically, these data suggest that adult males with a history of prenatal methamphetamine exposure may be at greater risk of developing cardiovascular disease due to endothelial dysfunction.

Gestational Exposure to Bisphenol A Affects Testicular Morphology, Germ Cell Associations, and Functions of Spermatogonial Stem Cells in Male Offspring.

Exposure to bisphenol A (BPA) in the gestational period damages the reproductive health of offspring; detailed evidence regarding BPA-induced damage in testicular germ cells of offspring is still limited. In this study, pregnant mice (F0) were gavaged with three BPA doses (50 μg, 5 mg, and 50 mg/kg body weight (bw)/day; tolerable daily intake (TDI), no-observed-adverse-effect-level (NOAEL), and lowest-observed-adverse-effect level (LOAEL), respectively) on embryonic days 7 to 14, followed by investigation of the transgenerational effects of such exposure in male offspring. We observed that the NOAEL- and LOAEL-exposed F1 offspring had abnormalities in anogenital distance, nipple retention, and pubertal onset (days), together with differences in seminiferous epithelial stages and testis morphology. These effects were eradicated in the next F2 and F3 generations. Moreover, there was an alteration in the ratio of germ cell population and the apoptosis rate in germ cells increased in F1 offspring at the LOAEL dose. However, the total number of spermatogonia remained unchanged. Finally, a reduction in the stemness properties of spermatogonial stem cells in F1 offspring was observed upon LOAEL exposure. Therefore, we provide evidence of BPA-induced disruption of physiology and functions in male germ cells during the gestational period. This may lead to several reproductive health issues and infertility in offspring.

Selenium-associated decrease of mir-216a and mir-217 expression in placenta and their associations with neurobehavioral development at birth: a genome-wide study of two U.S. birth cohorts

Background: As an essential micronutrient, selenium plays a vital role in fetal development. MicroRNA expression modification is a potential mechanism linking dietary exposures and fetal neurobehavioral development; however, very few studies have sought to elucidate whether microRNA expression is responsive to selenium in humans. We aimed to investigate the associations between selenium concentration in the placenta, a critical developmental organ, and microRNA expression, and to assess the association between selenium-associated microRNAs and newborns’ neurobehavior. Methods: Our study included 394 newborns (280 from New Hampshire Birth Cohort Study, 114 from Rhode Island Child Health Study). Placental selenium concentrations were quantified using inductively coupled plasma mass spectrometry, and genome-wide microRNA and mRNA transcripts were measured using RNA-seq. Newborn neurobehavioral development was assessed by the NICU Network Neurobehavioral Scales. We fitted generalized additive models with smoothing splines for selenium and microRNAs in the pooled data of the two cohorts, adjusting for covariates. We fitted multiple linear regression and ordinal logistic regression for microRNAs and newborn NNNS summary scores, adjusting for covariates. Results: We identified a reverse J-shaped association between selenium concentration and the expression of mir216a/mir217 cluster (edf = 2, FDR-adjusted p-value = 4.14 × 10-5) in placenta, and we observed that a doubling in mir216a/mir217 expression was associated with a 0.13 and 0.19 decrease in self-regulation score of newborns (p-value = 0.03 and 0.08). Moreover, self-regulation was positively associated with the expression of mir216a/mir217-targeted TXNRD2, a selenoprotein coding gene (β = 0.83, p-value = 0.04). Conclusions: The selenium-associated modification of mir216a/mir217 expression in the placenta might provide a partial mechanism for neurobehavioral developmental effects of prenatal selenium exposure in offspring.

The Impact of Circulating Antibody on Group B Streptococcus Intestinal Colonization and Invasive Disease.

Gastrointestinal (GI) colonization with group B Streptococcus (GBS) is an important precursor to late-onset (LO) disease in infants. The host-pathogen interactions that mediate progression to invasive disease remain unknown due, in part, to a paucity of robust model systems. Passively acquired maternal GBS-specific antibodies protect newborns from early-onset disease, yet their impact on GI colonization and LO disease is unexplored. Using murine models of both perinatal and postnatal GBS acquisition, we assessed the kinetics of GBS GI colonization, progression to invasive disease, and the role of GBS-specific IgG production in exposed offspring and juvenile mice at age 12 and 14 days, respectively. We defined LO disease as >7 days of life in the perinatal model. We studied the impact of maternal immunization using a whole-cell GBS vaccine on the duration of intestinal colonization and progression to invasive disease after postnatal GBS exposure in offspring. Animals exhibit sustained GI colonization following both perinatal and postnatal exposure to GBS, with 21% and 27%, respectively, developing invasive disease. Intestinal colonization with GBS induces an endogenous IgG response within 20 days of exposure. Maternal vaccination with whole-cell GBS induces production of GBS-specific IgG in dams that is vertically transmitted to their offspring but does not decrease the duration of GBS intestinal colonization or reduce LO mortality following postnatal GBS exposure. Both perinatal and postnatal murine models of GBS acquisition closely recapitulate the human disease state, in which GBS colonizes the intestine and causes LO disease. We demonstrate both endogenous production of anti-GBS IgG in juvenile mice and vertical transfer of antibodies to offspring following maternal vaccination. These models serve as a platform to study critical host-pathogen interactions that mediate LO GBS disease.

Impaired sperm quantity and motility in adult rats following gestational and lactational exposure to environmentally relevant levels of PBDE-47: A potential role of thyroid hormones disruption.

Polybrominated diphenyl ethers (PBDEs) are flame retardants and the congener 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) is capable of inducing thyroid endocrine disruption and developmental toxicity. However, little is known about whether developmental PBDE-47 exposure-elicited alterations in semen quality is associated with thyroid hormones (THs) perturbation. In this research, we sought to explore the impacts of gestational and lactational PBDE-47 exposure on adult sperm quantity and motility, and its link with THs levels. For this purpose, female Sprague-Dawley rats were administered environmentally relevant PBDE-47 levels (0.1, 1.0, 10mg/kg/day) by oral gavage from prepregnancy through lactation cessation to achieve early-life exposure of offspring and to mimic the actual exposure. Sperm quantity and motility together with serum THs levels from male offspring were determined on postnatal day 88. In utero and lactational exposure to PBDE-47 boosted the weight gain while reduced the relative testis weight in adult male offspring. These were accompanied with the reductions in sperm counts (total and living sperm counts), the percentage of progressive sperm motility, sperm velocities (curvilinear velocity, straight-line velocity and average path velocity), motion path (beat cross frequency, linearity and wobble) and linear motile sperm parameters (count, motility and concentration). Further studies identified that the levels of serum triiodothyronine (T3) were increased by PBDE-47 exposure and negatively associated with those differential semen parameters on quantity and motility. Collectively, our results indicate that exposure to low-level PBDE-47 during early-life development impairs semen quality in adult rats, which could be mediated partially by abnormal T3 levels.

The Endocrine Disruption of Prenatal Phthalate Exposure in Mother and Offspring.

Phthalates are a group of ubiquitous synthetic endocrine-disrupting chemicals. Fetal and neonatal periods are particularly susceptible to endocrine disorders, which prenatal exposure to phthalates causes. There is increasing evidence concerning the potential endocrine disrupting for phthalate exposure during pregnancy. This article aims to review the endocrine impairment and potential outcomes of prenatal phthalate exposure. Prenatal exposure phthalates would disrupt the levels of thyroid, sex hormone, and 25-hydroxyvitamin D in pregnant women or offspring, which results in preterm birth, preeclampsia, maternal glucose disorders, infant cryptorchidism, infant hypospadias, and shorter anogenital distance in newborns, as well as growth restriction not only in infants but also in early adolescence and childhood. The relationship of prenatal phthalate exposure with maternal and neonatal outcomes in human beings was often sex-specific associations. Because of the potentially harmful influence of prenatal phthalate exposure, steps should be taken to prevent or reduce phthalate exposure during pregnancy.

Association between metal cobalt exposure and the risk of congenital heart defect occurrence in offspring: a multi-hospital case-control study

BackgroundMany studies have investigated heavy metal exposure could increase the occurrence of congenital heart defects (CHDs). However, there are limited data regarding the relationship between cobalt exposure and CHD occurrence in offspring. The aim of this study was to analyze the association between cobalt exposure in mothers and the risk of CHDs in offspring.Materials and methodsIn order to explore the association between cobalt exposure and occurrence of congenital heart defect (CHD), a case-control study with 490 controls and 399 cases with CHDs in China were developed. The concentrations of cobalt in hair of pregnant woman and fetal placental tissue were measured and processed by a logistic regression analysis to explore the relationship between cobalt exposure and risk of CHDs.ResultsThe median concentration of hair cobalt in the control and case group was 0.023 ng/mg and 0.033 ng/mg (aOR, 1.837; 95% CI, 1.468–2.299; P < 0.001), respectively. And the median (5–95% range) fetal placental cobalt concentrations were 19.350 ng/g and 42.500 ng/g (aOR, 2.924; 95% CI, 2.211–3.868; P < 0.001) in the control and case groups, respectively. Significant differences in the middle level of cobalt in hair were found in the different CHD subtypes, including septal defects, conotruncal defects, right ventricular outflow tract obstruction, and left ventricular outflow tract obstruction (P < 0.001). Dramatically, different cobalt concentrations in fetal placental tissue were found in all subtypes of cases with CHDs (P < 0.01).ConclusionsThe finding suggested that the occurrence of CHDs may be associated with cobalt exposure.

Associations of Preconception Exposure to Air Pollution and Greenness with Offspring Asthma and Hay Fever.

We investigated if greenness and air pollution exposure in parents’ childhood affect offspring asthma and hay fever, and if effects were mediated through parental asthma, pregnancy greenness/pollution exposure, and offspring exposure. We analysed 1106 parents with 1949 offspring (mean age 35 and 6) from the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Mean particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), black carbon (BC), ozone (O3) (µg/m3) and greenness (normalized difference vegetation index (NDVI)) were calculated for parents 0–18 years old and offspring 0–10 years old, and were categorised in tertiles. We performed logistic regression and mediation analyses for two-pollutant models (clustered by family and centre, stratified by parental lines, and adjusted for grandparental asthma and education). Maternal medium PM2.5 and PM10 exposure was associated with higher offspring asthma risk (odds ratio (OR) 2.23, 95%CI 1.32–3.78, OR 2.27, 95%CI 1.36–3.80), and paternal high BC exposure with lower asthma risk (OR 0.31, 95%CI 0.11–0.87). Hay fever risk increased for offspring of fathers with medium O3 exposure (OR 4.15, 95%CI 1.28–13.50) and mothers with high PM10 exposure (OR 2.66, 95%CI 1.19–5.91). The effect of maternal PM10 exposure on offspring asthma was direct, while for hay fever, it was mediated through exposures in pregnancy and offspring’s own exposures. Paternal O3 exposure had a direct effect on offspring hay fever. To conclude, parental exposure to air pollution appears to influence the risk of asthma and allergies in future offspring.

Maternal occupational exposure and congenital heart defects in offspring.

Objectives:Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD.Methods:For this case–control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix.Results:An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (ORadj) 1.90, 95% confidence interval (CI) 1.01–3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (ORadj 2.68, 95% CI 1.07–6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (ORadj 2.94, 95% CI 1.21–7.13) and pulmonary valve stenosis (ORadj 1.99, 95% CI 1.10–3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (ORadj 2.40, 95% CI 1.09–5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (ORadj 3.23, 95% CI 1.14–9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (ORadj 0.32, 95% CI 0.11–0.94).Conclusions:Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development.