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PCB52 exposure alters the neurotransmission ligand-receptors in male offspring and contributes to sex-specific neurodevelopmental toxicity
2020
Zhao, Dong | Wang, Qi | Zhou, Wen-Tao | Wang, Li-Bin | Yu, Hao | Zhang, Kai-Kai | Chen, Li-Jian | Xie, Xiao-Li
Polychlorinated biphenyls (PCBs) in the air are predominantly the less chlorinated congeners. Non-dioxin-like (NDL) low-chlorinated PCBs are more neurotoxic, and cause neurodevelopmental and neurobehavioral alterations in humans. However, the underlying mechanisms for this neurodevelopmental toxicity remain unknown. In the present study, Wistar rats were treated by gavage with PCB52 (1 mg/kg body weight) or corn oil from gestational day 7 to postnatal day 21. Both the body lengths and weights of the suckling rats at birth were significantly decreased by PCB52 treatment, suggesting developmental toxicity. Although no obvious histopathological changes were observed in the brain, using RNA-sequencing, 208 differentially expressed genes (DEGs) were identified in the striatum of PCB52-treated male offspring, while just 13 DEGs were identified in female offspring, suggesting sex-specific effects. Furthermore, using Gene Ontology enrichment analysis, neurodevelopmental processes, neurobehavioral alterations, and neurotransmission changes were enriched from the 208 DEGs in male offspring. Similarly, using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, neuroactive ligand receptor interactions and multiple synapse pathways were enriched in male offspring, implying dysfunction of the neurotransmission system. Reductions in the protein expressions of these ligand receptors were also identified in the striatum, cerebral cortex, and hippocampus using western blotting methods. Taken together, our findings indicate that PCB52 exposure during gestation and lactation results in the abnormal expression of neurotransmission ligand-receptors in male offspring with a sex bias, and that this may contribute to neurodevelopmental toxicity.
Show more [+] Less [-]Parabens in breast milk and possible sources of exposure among lactating women in Korea
2019
Park, Na-Youn | Cho, Yoon Hee | Choi, Kyungho | Lee, Eun-hee | Kim, Yang Jee | Kim, Jung Hoan | Kho, Younglim
Parabens, broad-spectrum antimicrobial preservatives widely used in various consumer products and food, are suspected to be linked with several adverse health effects in humans, especially newborn babies, infants, and young children. While human exposure to parabens has been frequently reported by measuring the concentration of parabens in urine, similar measurements in breast milk have rarely been made. To determine paraben concentrations in breast milk and possible sources of exposure, four major parabens, including methylparaben (MP), ethylparaben (EP), propylparaben (PP), and butylparaben (BP) were measured in breast milk samples collected from 260 lactating women in South Korea. Demographic, socioeconomic, and behavioral factors associated with the presence of parabens in breast milk were determined. EP concentrations were detected at the highest levels in breast milk samples, followed by MP, PP, and BP. Pre-pregnancy BMI, parity, use of basic skin care products, use of cosmetics, canned beverage, and type of milk consumption were associated with higher frequencies of paraben detection. In addition, type of milk, parity, and drinking status were significantly associated with the concentration of EP. Multiple regression analyses showed that colostrum and transitional milk samples had higher levels of EP than mature milk samples. The estimated daily intake of parabens in infants via breastfeeding appears to be negligible when compared to the acceptable daily intake values set forth by the European Food Safety Authority (EFSA); however, considering the vulnerability of breastfed infants and ubiquitous sources of exposure from daily use of household and personal toiletries, efforts to identify sources and mitigate exposure are warranted.
Show more [+] Less [-]Maternal transfer of phenol derivatives in the Baltic grey seal Halichoerus grypus grypus
2018
Nehring, Iga | Falkowska, Lucyna | Staniszewska, Marta | Pawliczka, Iwona | Bodziach, Karina
Studies of circulating levels in difference sex and age classes, and maternal transfer of bisphenol A, 4-tert-octylphenol and 4- nonylphenol in the Baltic grey seal were performed from 2014-2017. Blood was collected from long-term captive adult males, pregnant females and pups. Milk was collected from nursing females. The aim of this study was not only to determine the concentrations of phenol derivatives, i.e. bisphenol A (BPA), 4-tert-octylphenol (OP) and 4-nonylphenol (NP), but also to try to evaluate the transfer of these compounds to the next generation in the final stage of foetal life and in the first few weeks of life in juvenile marine mammals. The measurements were carried out using high performance liquid chromatography. The obtained data show that all phenol derivatives are present in the blood of males, females and pups (range <0.07–101 ng·cm⁻³) and in female milk (range <0.1–406.3 ng·cm⁻³). The main source of phenol derivatives in organisms is food exposure. Gender, age, or number of births were not observed to have a significant effect on changes in phenol derivative levels in seal blood within the breeding group. In the prenatal stage of life, a small amount of BPA and alkylphenols was passed on to the offspring through the placenta. In the blood of the offspring the concentration of these compounds exceeded the concentration in the mother's blood 1.5-fold. During nursing, females detoxified their systems. Level of phenol derivatives in the pups blood increased linearly with its increasing concentrations in the mother's milk. On the other hand, the seafood diet which started after the physiological fasting stage of the pup, stabilised the levels of phenol derivatives below 10 ng ∙ cm⁻³.
Show more [+] Less [-]Blood dynamics of mercury and selenium in northern elephant seals during the lactation period
2011
The effects of reproduction and maternal investment (i.e., milk transfer) on trace element levels remain poorly understood in marine mammals. We examined the blood dynamics of mercury (Hg) and selenium (Se) during lactation in the northern elephant seal (Mirounga angustirostris), a top predator from the North Pacific Ocean. Total Hg and Se levels were measured in whole blood and milk of 10 mother–pup pairs on days 5 and 22 of lactation. Both Hg and Se were transferred to offspring through the milk. Results suggested that the maternal transfer of Se was prominent during lactation, whereas the Hg transfer was larger during gestation. The lactation period affected Hg and Se levels in the blood of elephant seal mothers and pups. Physiological processes and their relationship to body condition should be considered carefully when interpreting trace element levels in the framework of biomonitoring.
Show more [+] Less [-]National survey of the levels of persistent organochlorine pesticides in the breast milk of mothers in China
2011
Zhou, Pingping | Wu, Yongning | Yin, Shian | Li, Jingguang | Zhao, Yunfeng | Zhang, Lei | Chen, Huijing | Liu, Yinping | Yang, Xin | Li, Xiaowei
The occurrence of persistent organochlorine pesticides (OCPs) in breast milk samples collected from mothers from twelve provinces in mainland China was investigated. Dichlorodiphenyltrichloroethanes (DDTs) were the most prevalent agent, followed by HCHs and HCB, whereas levels of chlordane compounds, drins and mirex were lower. The relatively lower DDE/DDT ratio in the Fujian rural area suggested more recent exposure to DDT than in other areas. The mean level of DDTs in breast milk from the southern China was higher than those from northern China (p < 0.05). A positive correlation was observed between concentration of DDTs in human milk and consumption of animal-origin food, suggesting that this parameter could play an important part in influencing OCPs burdens in lactating women. The mean estimated daily intakes of different OCPs for breastfed infants were lower than the tolerable daily intake.
Show more [+] Less [-]Varying modalities of perinatal exposure to a pesticide cocktail elicit neurological adaptations in mice and zebrafish
2021
Forner-Piquer, Isabel | Klement, Wendy | Gangarossa, Giuseppe | Zub, Emma | de Bock, Frederic | Blaquiere, Marine | Maurice, Tangui | Audinat, Etienne | Faucherre, Adèle | Lasserre, Frederic | Ellero-Simatos, Sandrine | Gamet-Payrastre, Laurence | Jopling, Chris | Marchi, Nicola
Epidemiological indications connect maternal and developmental presence or exposure to pesticides with an increased risk for a spectrum of neurological trajectories. To provide pre-clinical data in support of this hypothesis, we used two distinct experimental models. First, female and male mice were fed immediately prior to mating, and the resulting pregnant dams were continously fed during gestation and lactation periods using chow pellets containing a cocktail of six pesticides at tolerable daily intake levels. Male and female offspring were then tracked for behavioral and in vivo electrophysiological adaptations. Second, a zebrafish model allowed us to screen toxicity and motor-behavior outcomes specifically associated with the developmental exposure to a low-to-high concentration range of the cocktail and of each individual pesticide. Here, we report anxiety-like behavior in aging male mice maternally exposed to the cocktail, as compared to age and gender matched sham animals. In parallel, in vivo electrocorticography revealed a decrease in gamma (40–80 Hz) and an increase of theta (6–9 Hz) waves, delineating a long-term, age-dependent, neuronal slowing. Neurological changes were not accompanied by brain structural malformations. Next, by using zebrafish larvae, we showed an increase of all motor-behavioral parameters resulting from the developmental exposure to 10 μg/L of pesticide cocktail, an outcome that was not associated with midbrain structural or neurovascular modifications as assessed by in vivo 2-photon microscopy. When screening each pesticide, chlorpyrifos elicited modifications of swimming parameters at 0.1 μg/L, while other components provoked changes from 0.5 μg/L. Ziram was the single most toxic component inducing developmental malformations and mortality at 10 μg/L. Although we have employed non-equivalent modalities and timing of exposure in two dissimilar experimental models, these outcomes indicate that presence of a pesticide cocktail during perinatal periods represents an element promoting behavioral and neurophysiological modifications. The study limitations and the possible pertinence of our findings to ecotoxicology and public health are critically discussed.
Show more [+] Less [-]n-Butylparaben exposure through gestation and lactation impairs spermatogenesis and steroidogenesis causing reduced fertility in the F1 generation male rats
2020
Maske, Priyanka | Dighe, Vikas | Mote, Chandrashekhar | Vanage, Geeta
Parabens are class of preservatives used in vast majority of commercial products, and a potential Endocrine Disrupting Chemical (EDC). The present study was undertaken to delineate the effects of n-butylparaben on F1 male progeny exposed maternally through gestation and lactation via subcutaneous route. The F0 dams were given subcutaneous injections of n-butylparaben from gestation day (GD) 6 to postnatal day (PND) 21 with doses of 10, 100, 1000 mg/kg Bw/day in corn oil. The F1 male rats were monitored for pubertal development and sexual maturation; these were sacrificed on PND 30, 45 and 75. On PND 75, these F1 male rats were subjected for fertility assessment with unexposed female rats.A delayed testicular descent at 100 and 1000 mg/kg Bw dose and delayed preputial separation at 10 mg/kg Bw dose was observed in exposed F1 male rats. Decreased sperm count, motility and Daily Sperm Production was observed at 100 mg/kg Bw dose at PND 75. Interestingly, the sperm transit time in the epididymis was accelerated at this dose. Significant perturbed testicular expression of steroid receptors (ERα and β, AR), INSL3 and StAR genes with increased T and LH levels indicates direct effect on spermatogenesis and steroidogenesis. These F1 generation adult rats were sub-fertile with increased (%) pre- and post-implantation loss at 100 and 1000 mg/kg Bw/day dose. This is the first report on n-butylparaben highlighting the involvement of testicular leydig cells with accelerated sperm transit time leading to reduced fertility in the maternally exposed F1 male rats through estrogenic/anti-androgenic action.
Show more [+] Less [-]Short and long-term effects of bisphenol S (BPS) exposure during pregnancy and lactation on plasma lipids, hormones, and behavior in rats
2019
da Silva, Beatriz Souza | Pietrobon, Carla Bruna | Bertasso, Iala Milene | Lopes, Bruna Pereira | Carvalho, Janaine Cavalcanti | Peixoto-Silva, Nayara | Santos, Tatianne Rosa | Claudio-Neto, Sylvio | Manhães, Alex Christian | Oliveira, Elaine | de Moura, Egberto Gaspar | Lisboa, Patrícia Cristina
Bisphenol S (BPS) has replaced bisphenol A (BPA), a known non-persistent endocrine disrupting chemical, in several products. Considering that little is known regarding BPS effects, especially during critical windows of ontogenetic development, and that BPA, which is quite similar to BPS, is know to be transferred to the offspring via the placenta and milk, in the present study we investigated the behavioral, biochemical and endocrine profiles of Wistar rats born from dams that were BPS-exposed [groups: BPS10 (10 μg/kg/day), BPS50 (50 μg/kg/day)] during pregnancy and lactation. Due to the non-monotonic dose-response effect of bisphenol, the data of both BPS groups were directly compared with those of the controls, not to each other. Males and females were analyzed separately. At weaning, male BPS50 offspring had hypotriglyceridemia and hyperthyroxinemia, whereas BPS50 females showed higher 25(OH)D levels. At adulthood, BPS offspring of both sexes had lower food intake. BPS males showed lower visceral adiposity. BPS50 females had smaller fat droplets in brown adipocytes. BPS males showed higher anxiety and higher locomotor activity, while BPS10 females showed lower exploration. During a food challenge test at adulthood, BPS males consumed more high-fat diet at 30 min. BPS10 females initially (at 30 min) consumed more high-fat diet but, after 12 h, less of this diet was consumed. BPS50 males had hypertriglyceridemia and lower plasma T3, while BPS females showed lower plasma T4. BPS10 females had lower progesterone, whereas BPS50 females had higher plasma 25(OH)D. Maternal BPS exposure has adverse effects on the triacylglycerol, hormones levels and behavior of the progeny. Furthermore, the increased preference for the fat-enriched diet suggests an increased risk for obesity and its health consequences in the long term.
Show more [+] Less [-]A pilot study on health risk assessment based on body loadings of PCBs of lactating mothers at Taizhou, China, the world's major site for recycling transformers
2017
Man, Yu Bon | Chow, Ka Lai | Xing, Guan Hua | Chan, Janet Kit Yan | Wu, Sheng Chun | Wong, Ming Hung
Our early study reported an extraordinarily high Estimated Daily Intake (EDI) of PCBs of lactating mothers from Taizhou, Zhejiang Province, China (based on a food consumption survey and food basket analysis). The EDI well exceeded the intake limit stipulated by FAO/WHO 70 pg TEQ/kg body weight (bw)/month. The present pilot study provided further information on PCBs body burden in lactating mothers of Taizhou. The total PCBs detected in human milk, placenta and hair samples of these lactating mothers were 363 ng/g lipid, 224 ng/g lipid, and 386 ng/g dry wt. Respectively, three times higher than those samples collected from the reference site (Lin'an). Compared with the previous reported values in the 3rd WHO coordinated study, Taizhou topped the list of 32 countries/regions with regards to WHO-PCB-TEQ values of milk samples, which could be attributed to the relatively higher level of PCB-126 derived from electronic waste. In addition, the corresponding EDI of PCBs of Taizhou mothers (12.9 pg WHO-PCB-TEQ/kg bw/day) and infants (438 pg WHO-PCB-TEQ/kg) were derived from individual congener levels in human milk. The results were also higher than the tolerable daily intakes recommended by WHO (1–4 pg WHO-TEQ/kg bw/day) by 3 and 110 times, for mothers and infants, respectively. A more intensive epidemiological study on the potential health effects of e-waste recycling activities affecting both workers and residents seems to be of top priority, based on findings of this pilot study.
Show more [+] Less [-]Perinatal multiple exposure to neurotoxic (lead, methylmercury, ethylmercury, and aluminum) substances and neurodevelopment at six and 24 months of age
2014
Marques, Rejane C. | Bernardi, José V.E. | Dórea, José G. | de Fatima R Moreira, Maria | Malm, Olaf
We studied neurodevelopment in infants from two communities. Children living in the vicinity of tin-ore kilns and smelters – TOKS; n = 51) were compared to children from a fishing village (Itapuã; n = 45). Mean hair-Hg (HHg) concentrations were significantly higher in Itapuã children which received significantly (p = 0.0000001) less mean ethylmercury (88.6 μg) from Thimerosal-containing vaccines (TCV) than the TOKS children (120 μg). Breast-milk Pb concentrations were significantly higher in the TOKS mothers (p = 0.000017; 10.04 vs. 3.9 μg L−1). Bayley mental development index (MDI) and psychomotor development index (PDI) were statistically significant (respectively p < 0.0000001, p = 0.000007) lower for the TOKS children only at 24 months of age. Multivariate regression analysis showed that MDI was negatively affected by breast-milk Pb and by HHg. PDI was positively affected by breastfeeding and negatively affected by ethylmercury. Milestone achievements were negatively affected by breast-milk Pb (age of walking) and by HHg (age of talking).
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