Sex differences in embryonic gonad transcriptomes and benzo[a]pyrene metabolite levels after transplacental exposure

Endocrinology ◽  
2021 ◽  
Author(s):  
Jinhwan Lim ◽  
Aramandla Ramesh ◽  
Toshi Shioda ◽  
Kathleen Leon ◽  
Ulrike Luderer

Abstract Polycyclic aromatic hydrocarbons like benzo[a]pyrene (BaP) are generated during incomplete combustion of organic materials. Prior research has demonstrated that BaP is a prenatal ovarian toxicant and carcinogen. However, the metabolic pathways active in the embryo and its developing gonads and the mechanisms by which prenatal exposure to BaP predisposes to ovarian tumors later in life remain to be fully elucidated. To address these data gaps, we orally dosed pregnant female mice with BaP from E6.5-11.5 (0, 0.2 or 2 mg/kg-day) for metabolite measurement or E9.5-11.5 (0 or 3.33 mg/kg-day) for embryonic gonad RNA-sequencing. Embryos were harvested at E13.5 for both experiments. The sum of BaP metabolite concentrations increased significantly with dose in the embryos and placentas, and concentrations were significantly higher in female than male embryos and in embryos than placentas. RNA sequencing revealed that enzymes involved in metabolic activation of BaP are expressed at moderate to high levels in embryonic gonads and that greater transcriptomic changes occurred in the ovaries in response to BaP than in the testes. We identified 490 differentially expressed genes (DEGs) with FDR p-values <0.05 when comparing BaP-exposed to control ovaries, but no statistically significant DEGs between BaP-exposed and control testes. Genes related to monocyte/macrophage recruitment and activity, prolactin family genes, and several keratin genes were among the most upregulated genes in the BaP-exposed ovaries. Results show that developing ovaries are more sensitive than testes to prenatal BaP exposure, which may be related to higher concentrations of BaP metabolites in female embryos.

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 644
Author(s):  
Do-Yeong Kim ◽  
Boram Kim ◽  
Han-Seung Shin

The effect of cellulosic aerogel treatments used for adsorption of four polycyclic aromatic hydrocarbons (PAHs)—benzo[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene [BaP])—generated during the manufacture of sesame oil was evaluated. In this study, eulalia (Miscanthus sinensis var. purpurascens)-based cellulosic aerogel (adsorbent) was prepared and used high performance liquid chromatography with fluorescence detection for determination of PAHs in sesame oil. In addition, changes in the sesame oil quality parameters (acid value, peroxide value, color, and fatty acid composition) following cellulosic aerogel treatment were also evaluated. The four PAHs and their total levels decreased in sesame oil samples roasted under different conditions (p < 0.05) following treatment with cellulosic aerogel. In particular, highly carcinogenic BaP was not detected after treatment with cellulosic aerogel. Moreover, there were no noticeable quality changes in the quality parameters between treated and control samples. It was concluded that eulalia-based cellulosic aerogel proved suitable for the reduction of PAHs from sesame oil and can be used as an eco-friendly adsorbent.


2019 ◽  
Vol 26 (11) ◽  
pp. 1485-1492
Author(s):  
Xiaochun Yi ◽  
Jie Zhang ◽  
Huixiang Liu ◽  
Tianxia Yi ◽  
Yuhua Ou ◽  
...  

The adverse clinical result and poor treatment outcome in recurrent spontaneous abortion (RSA) make it necessary to understand the pathogenic mechanism. The mating combination CBA/J × DBA/2 has been widely used as an abortion-prone model compared to DBA/2-mated CBA/J mice. Here, we used RNA-seq to get a comprehensive catalogue of genes differentially expressed between survival placenta in abortion-prone model and control. Five hundred twenty-four differentially expressed genes were obtained followed by clustering analysis, Gene Ontology analysis, and pathway analysis. We paid more attention to immune-related genes namely “immune response” and “immune system process” including 33 downregulated genes and 28 upregulated genes. Twenty-one genes contribute to suppressing immune system and 7 are against it. Six genes were validated by reverse transcription-polymerase chain reaction, namely Ccr1l1, Tlr4, Tgf-β1, Tyro3, Gzmb, and Il-1β. Furthermore, Tlr4, Tgf-β1, and Il-1β were analyzed by Western blot. Such immune profile gives us a better understanding of the complicated immune processing in RSA and immunosuppression can rescue pregnancy loss.


2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.


2019 ◽  
Author(s):  
Hoang T. M. D. Le ◽  
Kai K. Lie ◽  
Angela Etayo ◽  
Ivar Rønnestad ◽  
Øystein Sæle

AbstractThe transcriptome of nutrient sensing and the regulation of gut motility by nutrients in a stomachless fish with a short digestive tract; the ballan wrasse (Labrus berggylta) were investigated. Using an in vitro model, we differentiate how signals initiated by physical stretch and nutrients modulate the gut evacuation rate and motility patterns, and transcriptomic changes. Stretch on the intestine by inert cellulose initiated fast evacuation out of the anterior intestine compared to the digestible protein and lipid. Stretch on the intestine upregulated genes associated with increased muscle activity, whereas nutrients stimulated pathways related to ribosomal activity and the increase in the expression of several neuropeptides which are directly involved in gut motility regulation. Our findings show that physical pressure in the intestine initiate contractions propelling the matter towards the exit, whereas the sensing of nutrients modulates the motility to prolong the residence of digesta in the digestive tract for optimal digestion.Summary statementPressure by food speed up peristalsis in the intestine, but the intestines ability to sense nutrients slow down peristalsis for better digestion. This is partly controlled by genetic regulation.


2020 ◽  
Author(s):  
Yan Lin ◽  
Yifang Zhu ◽  
Xinghua Qiu ◽  
Fen Yin ◽  
Chi-Hong Tseng ◽  
...  

Abstract Background: There are drastic differences in smoking prevalence and control policies among different countries. However, the impact of international travels on passive smoking exposures and subsequent health effects remained unknown. Methods: We recruited 27 non-smokers who travelled from Los Angeles to Beijing for 10 weeks in 2014 and 2015. Urine samples (n=197) were collected before (LA-before), during (Beijing), and after (LA-after) the trip, for the assessment of biomarkers of passive smoking (cotinine), PAHs exposure (hydroxylated-PAHs), and lipid peroxidation (malondialdehyde and 8-isoprostane). Results: The geometric mean concentrations of urinary cotinine were 0.13, 1.50, and 0.22 µg/g creatinine in LA-before, Beijing, and LA-after, respectively. Likewise, hydroxylated-PAH levels were significantly higher in Beijing as compared to LA-before or LA-after (p<0.001), in association with the urinary cotinine concentrations (p<0.05). Traveling from Los Angeles to Beijing increased urinary concentrations of malondialdehyde by 51.8% (95%CI, 29.1% to 78.5%), which did not return to baseline levels, up to 4 - 10 weeks after traveling back to Los Angeles. Remarkably, while urinary 8-isoprostane concentrations were similar between Beijing and LA-before, those levels increased by 75.5% (95%CI, 48.5% to 108%) after returning to Los Angeles (LA-after), and were significantly higher than baseline (LA-before, 63.6%; 95%CI, 31.1% to 104%). Urinary concentrations of malondialdehyde and 8-isoprostane were positively associated with urinary cotinine concentrations, independently of hydroxylated-PAHs. Conclusion: Traveling from Los Angeles to Beijing increased exposures to passive smoking, which contributed to increased PAHs exposures and increased lipid peroxidation in the urine.Trial Registration: Not applicable.


2022 ◽  
Vol 12 ◽  
Author(s):  
Beatrice E. Gee ◽  
Andrea Pearson ◽  
Iris Buchanan-Perry ◽  
Roger P. Simon ◽  
David R. Archer ◽  
...  

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)—based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p &lt; 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p &lt; 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p &lt; 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA.


Author(s):  
Jumbo Adata Akie ◽  
M.O Wegwu ◽  
D. C. Belonwu ◽  
B. M. Onyegeme-Okerenta ◽  
C. T. Iriakuma

Polycyclic aromatic hydrocarbon (PAH) content in selected fin and shell fishes from Bodo and Kaa in Ogoniland were studied. PAH was determined by Gas chromatography, using Texas Natural Resource Conversion Commission, Texas (TNRCC TX) method. There was a total of 16 PAHs detected in the samples from the two sites, test site (Bodo) and control site (Kaa). Similar PAH accumulations were observed in the four species, but the concentrations of the PAH accumulations were different. For samples from Kaa, Mullet showed the highest total mean concentration of PAHs followed by Sompat grunt, Tilapia and the least was Shrimps. However, for samples collected from Bodo, Tilapia showed the highest total mean concentration of PAHs, followed by Sompat grunt, Shrimps, and the least Mullet. These findings were not definitive as to the source of the PAH, seemingly suggesting various or multiple sources of PAHs contamination in the studied sites. These variations may be attributed to their feeding habits. The mean and standard deviations for PAHs from the test site ranged from 0.08±.000b to 23.7±.473b, 0.05±.001b to 7.74±.346b, 0.02±.001b to 9.48±.002b, 0.07±.000b to 11.0±.029b for Tilapia, Mullet, Shrimps and Sompat grunt respectively and 0.18±.006a to 6.56±.064a, 0.08±.000a to 11.8±.555a, 0.05±.002a to 3.11±.036a, 0.05±.002a to 5.12±.059a for samples of Tilapia, Mullet, Shrimp and Sompat grunt respectively from the control site. In conclusion, the calculated potency equivalence concentration (PEC) for all the tested aquatic species collected from Kaa and Bodo were all above the screening value (SV) suggesting that the consumption of these aquatic species from the test and control site at a rate of 68g/day in an adult of about 60kg will expose the individual to a potential risk of cancer.


2020 ◽  
Vol 10 (14) ◽  
pp. 4951
Author(s):  
Helena Lopes ◽  
Susana Proença

Since ashes are a possible source of Persistent Organic Pollutants (POPs) contamination, their application in soils must be subject to more study and control. In this scope, feed residual forest biomasses and biomass ashes, collected along one year in four biomass power stations, were characterized mainly for their polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) and Polycyclic Aromatic Hydrocarbons (PAHs) contents. The biomasses present concerning levels of Cl (0.04–0.28%) that may lead to PCDD/Fs formation. The biomasses also contain OCDD (29–260 ng/kg) and 1,2,3,4,6,7,8-HpCDD (35 ng/kg) that may contribute to increased Toxic Equivalents (TEQs) of ashes, possibly involving dechlorination and ash enrichment mechanisms. While the WHO2005-TEQs in bottom ashes (14–20 ng TEQ/kg) reaches the proposed limit (20 ng TEQ/kg) for ash use as fertilizers, in fly ashes (35–1139 ng TEQ/kg) the limit is exceeded. PAHs are below 0.02 mg/kg in bottom ashes and 1.5–2.5 mg/kg in fly ashes, complying with the proposed limit of 6 mg/kg. As bottom and fly ash streams may contain different ash flows, a clear definition of ash mixes is required. Correlations between unburned carbon (C), PAHs and PCDD/Fs were not found, which highlights the need for compulsory PCDD/Fs analysis in ashes, independently of their origin, burnout degree or levels of other contaminants. A sensitivity analysis was performed to evaluate the impact of handling non-detected values, which showed more impact for TEQs values close to the proposed regulatory limit of PCDD/Fs. These findings highlight the need to define reporting protocols of analytical results for risk assessments and conformity evaluation.


2016 ◽  
Vol 04 (01) ◽  
pp. 041-043 ◽  
Author(s):  
Arun Kumar ◽  
Manohar Bhatia ◽  
Pawan Goel ◽  
Ram Jain

AbstractDiabetes mellitus (DM), commonly regarded as a lifestyle disease, used to be a disease of affluent societies in the days of yore. However, now it has encroached into the rural and tribal communities as well. This narrative review provides us with an understanding of the epidemiology of diabetes burden in tribes of India. Around 15% of the country′s area is covered by tribals and it constitutes ~8.6% (i. e., ~104 million) of India′s total population. Prevalence of diabetes in tribal areas ranges from around 1% to 10%. Hence, intensive efforts directed towards filling the gaps in awareness levels and the operational research or other data gaps would help prevent and control the problem of diabetes and fill these gaps in tribal areas.


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