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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.
Mostrar más [+] Menos [-]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.
Mostrar más [+] Menos [-]Bisphenol analogue concentrations in human breast milk and their associations with postnatal infant growth
2020
Jin, Hangbiao | Xie, Jiahui | Mao, Lingling | Zhao, Meirong | Bai, Xiaoxia | Wen, Jie | Shen, Tao | Wu, Pengfei
Many studies show that bisphenol A (BPA) is widespread in human breast milk. However, the occurrence of other bisphenol analogues (BPs), including bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF), in breast milk is still not well known. In this study, breast milk samples were collected from 190 women in Hangzhou, China, with the aims to characterize the occurrence of BPA, BPS, BPF, and BPAF in these samples and to investigate their effects on postnatal growth of infants through breast milk consumption. BPA (mean 2.5 ng/mL, range < LOD–15 ng/mL) was the most abundant BP in breast milk, followed by BPS (0.19 ng/mL, <LOD–1.3 ng/mL) and BPAF (0.092 ng/mL, <LOD–0.58 ng/mL). BPF was not detected in all breast milk samples. We firstly found that breast milk concentrations of BPA were negatively correlated with infant’s weight or length gain rate. Daily intakes (DIs) of BPs via the consumption of breast milk were calculated for infants, and the mean DI values were 531 ng/kg/day, 53 ng/kg/day, and 24 ng/kg/day for BPA, BPS, and BPAF, respectively. Overall, this study firstly demonstrats that the lactation exposure to BPA through breast milk consumption may affect the postnatal growth of infants.
Mostrar más [+] Menos [-]Regulation of lipid droplets via the PLCβ2-PKCα-ADRP pathway in granulosa cells exposed to cadmium
2020
In steroidogenic cells, steroids are synthesized de novo from cholesterol stored in lipid droplets (LDs). The size of LDs regulated by adipose differentiation-related protein (ADRP) is closely related to cholesterol ester hydrolysis. Many studies reported that cadmium (Cd) had dual effects on steroidogenesis in granulosa cells (GCs). However, the role of LD and its regulation in abnormal steroidogenesis caused by Cd exposure remain unknown. In current study, female rats were exposed to CdCl₂ during gestation and lactation, and influence of such exposure was investigated in ovarian GCs of female offspring. The size of LDs was found much smaller than normal in GCs; ADRP was down-regulated and hormone-sensitive lipase (HSL) phosphorylation was increased, followed by up-regulation of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (CYP11A1); the expression of 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 (PLCβ2) and protein kinase C alpha type (PKCα) were both decreased accompanying the ADRP down-regulation. This series of events resulted in a high level of progesterone in serum. Similar results were demonstrated in GCs treated with 20 μM CdCl₂ for 24 h in vitro. The protein level of ADRP was decreased after gene silencing of PLCβ2/PKCα, and the knockdown of PLCβ2/PKCα/ADRP led to micro-sized LD formation. We found that Cd exposure down-regulated ADRP by inhibiting the PLCβ2-PKCα signaling pathway, reduced the size of LDs, and promoted HSL phosphorylation. StAR and CYP11A1 were both up-regulated following the hydrolysis of cholesterol ester, which led to a high production of progesterone. LD thereby is a target subcellular organelle for Cd to affect steroid hormone synthesis in ovarian GCs. These findings might help to uncover the mechanism of ovarian dysfunction and precocious puberty caused by Cd pollution.
Mostrar más [+] Menos [-]Programming of hepatic lipid metabolism in a rat model of postnatal nicotine exposure – Sex-related differences
2020
Bertasso, Iala Milene | Pietrobon, Carla Bruna | Lopes, Bruna Pereira | Peixoto, Thamara Cherem | Soares, Patrícia Novaes | Oliveira, Elaine | Manhães, Alex Christian | Bonfleur, Maria Lucia | Balbo, Sandra Lucinei | Cabral, Suellen Silva | Gabriel Kluck, George Eduardo | Atella, Georgia Correa | Gaspar de Moura, Egberto | Lisboa, Patrícia Cristina
Maternal nicotine exposure during lactation induces liver damage in adult male rats. However, the mechanism in males is unknown and females have not been tested. Here, we determined the liver lipid composition and lipogenic enzymes in male and female offspring at two ages in a model of postnatal nicotine exposure. Osmotic minipumps were implanted in lactating Wistar rat dams at postnatal day (PND) 2 to release 6 mg/kg/day of nicotine (NIC group) or saline (CON group) for 14 days. Offspring received a standard diet from weaning until euthanasia at PND120 (1 pup/litter/sex) or PND180 (2 pups/litter/sex). At PND120, NIC males showed lower plasma triglycerides (TG), steatosis degree 1, higher hepatic cholesterol (CHOL) ester, free fatty acids, monoacylglycerol content as well as acetyl-coa carboxylase-1 (ACC-1) and fatty acid synthase (FAS) protein expression in the liver compared to CON males. At this age, NIC females had preserved hepatocytes architecture, higher plasma CHOL, higher CHOL ester and lower total CHOL content in the liver compared to CON females. At PND180, NIC males showed steatosis degrees 1 and 2, higher TG, lower free fatty acids and total CHOL content in the liver and an increase in ACC-1 hepatic protein expression. NIC females had higher plasma TG and CHOL levels, no change in hepatic morphology, lower CHOL ester and free fatty acids in the liver, which also showed higher total ACC-1 and FAS protein expression. Maternal nicotine exposure induces long-term liver dysfunction, with an alteration in hepatic cytoarchitecture that was aggravated with age in males. Concerning females, despite unchanged hepatic cytoarchitecture, lipid metabolism was compromised, which deserves further attention.
Mostrar más [+] Menos [-]Organochlorine pesticides (HCH and DDT) in blubber of spotted seals (Phoca largha) from the western Sea of Japan
2020
Trukhin, Alexey M. | Boyarova, Margarita D.
In 2014–2019, a total of 31 blubber samples were collected from spotted seals (Phoca largha) in the western Sea of Japan. The samples were analyzed by gas chromatography to determine level of organochlorine pesticides (OCPs). The concentration of hexachlorocyclohexane and its isomers (∑HCH) ranged from 389 to 50,070 ng/g lipid weght; the concentration of dichlorodiphenyltrichloroethane and its metabolites (∑DDT), ranged from 62,720 to 1,110,930 ng/g lipid wt. Transfer of HCH and DDT from mother to pup during pregnancy and lactation was documented. The OCP concentration in blubber of spotted seals from the western Sea of Japan is one to two orders of magnitude higher than in spotted seals inhabiting waters off the Japan coast. Organochlorines detected in the western Sea of Japan likely come from some countries of Southeast Asia still using OCPs in the agriculture sector.
Mostrar más [+] Menos [-]Abatement of enteric methane production from lactating Murrah buffaloes (Bubalus bubalis) with improving production performance and immune status through dietary supplementation of composite feed additive
2020
Attri, Kiran | Dey, Avijit | Dahiya, Satbir Singh | Paul, Shyam Sundar | Jerome, Andonissamy | Bharadwaj, Anurag | Kakker, Naresh Kumar
Ruminant livestock production processes are the major sources of methane production in agriculture sector triggering global environmental pollution. Above 90% of world buffalo population present in Asian countries, India ranks first and contributes significantly to the environmental pollution by enteric methane emissions. In this study, we examined the effect of dietary composite feed additive supplementation on ruminal methane production, nutrient utilization, milk production and immune status of buffaloes (Bubalus bubalis). Eighteen lactating Murrah (Bubalus bubalis) buffaloes at early stage of lactation were divided into two groups of nine animals and fed a composite feed additive [consisted of (%, w/w) dried and ground leaves of Cordia dichotoma and Holoptelea integrifolia, 31.4 each; garlic oil, 0.6; sodium nitrate, 3.1; magnesium sulphate, 8.4; mustard oil, 12.6 and cottonseed oil, 12.5] which contained an ideal combinations of methane inhibitors, alternate hydrogen sinks and rumen stimulating agents to treatment (CFA) group animals along with basal feed of chaffed green sorghum (Sorghum bicolor) fodder, chaffed wheat straw and concentrate mixture for maintenance and milk production. The results showed a decrease (44.6%) in methane concentration in exhaled air of CFA group buffaloes with increase (p < 0.05) in digestibility of feed in comparison to control (CON). Total digestible nutrient (TDN) content of the ration fed to buffaloes of CFA group was significantly (p < 0.05) increased. The daily milk yield, 6% fat corrected milk (FCM) yield and immune response were also increased (p < 0.05) in CFA group. The study suggests that the supplementation of composite feed additive was effective to reduce enteric methane emissions and improvement in production performance and immune status of buffaloes.
Mostrar más [+] Menos [-]Impairment of testicular development in rats exposed to acephate during maternal gestation and lactation
2020
Sampaio, Carolina Ferreira | Prates, Kelly Valério | Siervo, Gláucia Eloisa Munhoz Lion | Mathias, Paulo Cézar de Freitas | Fernandes, Glaura Scantamburlo Alves
Acephate is an organophosphate insecticide that disrupts the endocrine system and impairs the male reproductive system. Thus, the aim of the present study was to evaluate whether exposure to acephate during maternal gestation and lactation histologically damages the testes of male Wistar rats in adulthood. For this study, adult Wistar rats were divided into the following groups: ACE-mother, (2.5 mg/kg/bw, gestational day (GD) 7 to postnatal day (PND) 21) and oil-mother (corn oil (control), GD 7 to PND 21). The male offspring (PND 90) were euthanized, and the prostates and testes were collected and weighed. The testes were utilized for histopathological analyses and to determine the sperm count. A spermatogenesis kinetic analysis revealed an increased number of seminiferous tubules in stages I–VI in the ACE-mother group. Additionally, we observed a decrease in the epithelium and the diameters of the evaluated seminiferous tubules and in the number of Sertoli cells in the group exposed to acephate. The sperm count analysis showed no difference between the groups. We conclude that maternal exposure to the pesticide acephate did not affect testicular function, but led to the impairment of testicular development and morphology of the tissue in adulthood.
Mostrar más [+] Menos [-]Oxidative Stress and DNA methylation in male rat pups provoked by the transplacental and translactational exposure to bisphenol A
2020
El Henafy, Hanan M. A. | Ibrahim, Marwa A. | Abd El Aziz, Samy A. | Gouda, Eman M.
The epigenetic changes induced by environmental contaminants play important roles in the inheritance of male reproductive dysfunction. The present study investigated DNA methylation changes and some oxidative stress biomarkers induced by bisphenol A (BPA) in male offspring. A total number of 48 female albino rats were administered orally with 50 μg/kg of BPA/day during gestation and/or lactation periods. At postnatal day 60, the samples were collected from the male pups to assess the serum testosterone, malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase (GSH-Px) activities in testicular tissue. DNA methylation in both DNA (cytosine-5)-methyltransferase 3A and estrogen receptor alpha genes was detected by methylation-specific PCR. BPA exposure resulted in significant decrease in the anogenital distance, testis and epididymis weights, serum testosterone level, SOD, GST, and GSH-Px levels with significant increase in weaning body weight and the MDA level. Additionally, BPA caused marked hypermethylation within Dnmt3A and ER- ∝ genes promoter regions in the testis of rat male pups. Graphical abstract
Mostrar más [+] Menos [-]Correction to: Impairment of testicular development in rats exposed to acephate during maternal gestation and lactation
2020
Sampaio, Carolina Ferreira | Prates, Kelly Valério | Siervo, Gláucia Eloisa Munhoz Lion | de Freitas Mathias, Paulo Cezar | Fernandes, Glaura Scantamburlo Alves
The original publication of this paper contains a mistake.
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