oru.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 30) Show all publications
Bereketoglu, C., Pradhan, A. & Olsson, P.-E. (2020). Nonsteroidal anti-inflammatory drugs (NSAIDs) cause male-biased sex differentiation in zebrafish. Aquatic Toxicology, 223, Article ID 105476.
Open this publication in new window or tab >>Nonsteroidal anti-inflammatory drugs (NSAIDs) cause male-biased sex differentiation in zebrafish
2020 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 223, article id 105476Article in journal (Refereed) Published
Abstract [en]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used pharmaceuticals to treat pain, fever and inflammation. NSAIDs are also known to have many side effects including adverse effects on reproduction in both humans and animals. As NSAIDs usage is not regulated they are frequently detected at high concentrations in the environment. In order to understand the effect of NSAIDs on zebrafish sex differentiation, we used seven different NSAIDs which were either Cox-1 selective, Cox-1 biased, non-selective or COX-2 selective. We show that at higher concentration, NSAIDs are toxic to zebrafish embryo as they lead to mortality and hatching delay. Gene expression analysis following short term exposure of NSAIDs led to downregulation of female specific genes including zp2, vtg2 foxl2 and wnt4. Long term exposure of larvae to environmentally relevant concentrations of Cox-2 selective and non-selective NSAIDs resulted in male-biased sex ratio which confirmed the qRT-PCR analysis. However, the Cox-1 selective acetylsalicylic acid and the Cox-1 biased ketoprofen did not alter sex ratio. The observed male-biased sex ratio could also be due to induction of apoptosis process as the genes including p21 and casp8 were significantly upregulated following exposure to the Cox-2 selective and the non-selective NSAIDs. The present study indicates that NSAIDs alter sex differentiation in zebrafish, primarily through inhibition of Cox-2. This study clearly demonstrates that the use of NSAIDs and their release into the aquatic environment should be carefully monitored to avoid adverse effects to the aquatic organisms. 

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Pain killers, Reproduction, Sex ratio, Toxicity, Water pollution
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:oru:diva-81652 (URN)10.1016/j.aquatox.2020.105476 (DOI)000531077200005 ()32315829 (PubMedID)2-s2.0-85083306210 (Scopus ID)
Funder
Swedish Research Council, 201504600Knowledge Foundation, 20150084
Note

Funding Agency:

Örebro University

Available from: 2020-05-08 Created: 2020-05-08 Last updated: 2020-05-25Bibliographically approved
Pradhan, A., Bereketoglu, C., Martin, L., Duhagon, J. & Olsson, P.-E. (2020). The food preservative ethoxyquin impairs zebrafish development, behavior and alters gene expression profile. Food and Chemical Toxicology, 135, Article ID 110926.
Open this publication in new window or tab >>The food preservative ethoxyquin impairs zebrafish development, behavior and alters gene expression profile
Show others...
2020 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 135, article id 110926Article in journal (Refereed) Published
Abstract [en]

In the present study, we investigated the detrimental effects of ethoxyquin (EQ) on zebrafish embryonic development using different endpoints including lethality, malformations, locomotion and gene expression. EQ is primarily used as a preservative in animal feed and it has been shown to have negative impacts on different laboratory animals. However, studies on the adverse effects of EQ in aquatic animals are still limited. In this study, zebrafish eggs were exposed to different concentrations of EQ ranging from 1 to 100 μM for six days. In the 100 μM treated groups 95 and 100% mortality was observed at 24 and 48 h, respectively. Delayed development, decreased pigmentation and pericardial edema were observed in larvae. Behavioral analysis of larvae demonstrated a distinct locomotive pattern in response to EQ both in light and dark indicating a possible developmental neurotoxicity and deficits in locomotion. The expression levels of genes involved in several physiological pathways including stress response, cell cycle and DNA damage were altered by EQ. Our results demonstrate that EQ could cause developmental and physiological toxicity to aquatic organisms. Hence, its toxic effect should be further analyzed and its use and levels in the environment must be monitored carefully.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Development defects, Edema, Gene expression, Mortality, Toxicity
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-78987 (URN)10.1016/j.fct.2019.110926 (DOI)000509791400034 ()31676350 (PubMedID)2-s2.0-85074726203 (Scopus ID)
Funder
Knowledge Foundation
Note

Funding Agency:

Örebro University

Available from: 2020-01-14 Created: 2020-01-14 Last updated: 2020-02-28Bibliographically approved
Shu, T., Zhai, G., Pradhan, A., Olsson, P.-E. & Yin, Z. (2020). Zebrafish cyp17a1 Knockout Reveals that Androgen-Mediated Signaling is Important for Male Brain Sex Differentiation. General and Comparative Endocrinology, 295, Article ID 113490.
Open this publication in new window or tab >>Zebrafish cyp17a1 Knockout Reveals that Androgen-Mediated Signaling is Important for Male Brain Sex Differentiation
Show others...
2020 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 295, article id 113490Article in journal (Refereed) Epub ahead of print
Abstract [en]

Brain sex differentiation is a complex process, wherein genes and steroid hormones act to induce specific gender brain differentiation. Testosterone (T) derived from the gonads has been linked to neural circuit modeling in a sex-specific manner. Previously, we have shown that cyp17a1 knockout (KO) zebrafish have low plasma androgen levels, and display compromised male-typical mating behaviors. In this study, we demonstrated that treatment of cyp17a1 KO males with T or 11-ketotestosterone (11-KT) is sufficient to rescue mating impairment by restoring the male-typical secondary sex characters (SSCs) and mating behaviors, confirming an essential role of androgen in maintaining SSCs and mating behaviors. Brain steroid hormone analysis revealed that cyp17a1 KO fish have reduced levels of T and 11-KT. We performed RNA sequencing on brain samples of control and cyp17a1 KO male zebrafish to get insights regarding the impact of cyp17a1 KO on gene expression pattern, and to correlate it with the observed disruption of male-typical mating behaviors. Transcriptome analysis of cyp17a1 KO males showed a differential gene expression when compared to control males. In total, 358 genes were differentially regulated between control males and KO males. Important genes including brain aromatase (cyp19a1b), progesterone receptor (pgr), deiodinase (dio2), and insulin-like growth factor 1 (igf1) that are involved in brain functions, as well as androgen response genes including igf1, frem1a, elovl1a, pax3a, mmp13b, hsc70, ogg1 were regulated. RT-qPCR analysis following rescue of cyp17a1 KO with T and 11-KT further suggested that androgen-mediated signaling is disrupted in the cyp17a1 KO fish. Our results indicated that cyp17a1 KO fish have an incomplete masculinization and altered brain gene expression, which could be due to decreased androgen levels.

Place, publisher, year, edition, pages
Academic Press, 2020
Keywords
RNA sequencing, brain dimorphism, neurons, sexual dimorphism, steroids
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-81189 (URN)10.1016/j.ygcen.2020.113490 (DOI)32283058 (PubMedID)2-s2.0-85083333782 (Scopus ID)
Available from: 2020-05-08 Created: 2020-05-08 Last updated: 2020-05-08Bibliographically approved
Bereketoglu, C. & Pradhan, A. (2019). Comparative transcriptional analysis of methylparaben and propylparaben in zebrafish. Science of the Total Environment, 671, 129-139
Open this publication in new window or tab >>Comparative transcriptional analysis of methylparaben and propylparaben in zebrafish
2019 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 671, p. 129-139Article in journal (Refereed) Published
Abstract [en]

Parabens are widely used as preservatives in different commercial items including food, cosmetics and pharmaceuticals, and their wide use has resulted in accumulation in the environment. Parabens have been shown to have negative effects on animals as well as human health. In this study, we carried out a comprehensive study to determine the adverse effects associated with propylparaben (PP) and methylparaben (MP) on early developmental stages of zebrafish. Mortality, hatching, developmental abnormalities and gene expression profiles were investigated in embryos exposed to both compounds. The semi-static exposure conditions showed that both MP (>= 100 mu M) and PP (>= 10 mu M) are toxic to the embryos in a concentration-dependent manner and lead to developmental abnormality. Malformations such as spinal defects, pericardial edema, and pigmentation defects were observed following both MP and PP treatments. Hatching delay, mortality and developmental abnormality data indicate that PP is more toxic than MP. For gene expression analysis, 1 and 10 mu M doses of MP and PP were analyzed. Genes from physiological pathways including stress response, cell cycle and DNA damage, inflammation, fatty acid metabolism and endocrine functions were affected by MP and PP. The gene expression profiles show that parabens cause toxicity by inducing oxidative stress, DNA double-strand breaks, apoptosis as well as by altering fatty acid metabolism. Altered expression of androgen receptor (ar) and estrogen receptor 2 alpha (esr2a) indicates an antiandrogenic and estrogenic activity of parabens in zebrafish. Overall, the present study provides considerable information on the negative effects of MP and PP using physiological endpoints and motivates further studies to explore the molecular mechanism of the toxicity associated with parabens.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Toxicity, Gene expression, Stress response, Development abnormality
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-74628 (URN)10.1016/j.scitotenv.2019.03.358 (DOI)000466090500015 ()30928742 (PubMedID)2-s2.0-85063319552 (Scopus ID)
Funder
Knowledge Foundation
Note

Funding Agency:

Örebro University

Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved
Seyoum, A. & Pradhan, A. (2019). Effect of phthalates on development, reproduction, fat metabolism and lifespan in Daphnia magna. Science of the Total Environment, 654, 969-977
Open this publication in new window or tab >>Effect of phthalates on development, reproduction, fat metabolism and lifespan in Daphnia magna
2019 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 654, p. 969-977Article, review/survey (Refereed) Published
Abstract [en]

Phthalates are used as plasticizers to increase durability, resistivity and flexibility of plastic materials. The commonly used phthalate, diethylhexyl phthalate (DEHP) is used in different plastic materials like food packaging, toys and medical devices. DEHP has been linked to different toxicities in humans as well as in animals, and as a consequence other phthalates, including dibutyl phthalate (DBP) and diethyl phthalate (DEP) are being introduced. The increased use of phthalates has resulted in contamination of aquatic ecosystem and it directly threatens the aquatic life. In this study, we analyzed the effects of three phthalates DEHP, DEP and DBP using freshwater organism Daphnia magna. Although, exposure of the three phthalates at 1 and 10 μM did not result any lethality and hatching delay, the chronic exposure for 14 days resulted in reduction of body length. There was enhanced fat accumulation on exposure to all the phthalates, as indicated by oil red O staining. qRT-PCR analysis of genes involved in fat metabolism suggests that the increase in fat content could be due to inhibition of absorption and catabolism of fatty acids. Reproduction analysis showed that DBP and DEP did not alter fecundity but surprisingly, DEHP at 1 μM increased reproduction by 1.5 fold compared to control group. Phthalates also showed negative effect on lifespan as DEP at 10 μM and DBP at both 1 and 10 μM significantly reduced the lifespan. Our data indicates that along with the banned phthalate DEHP, the other substitute phthalates DEP and DBP could also have detrimental effect on aquatic organisms.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Plasticizer, Metabolism, Toxicity, Lipid, Gene expression
National Category
Biological Sciences Environmental Sciences
Research subject
Biology
Identifiers
urn:nbn:se:oru:diva-71876 (URN)10.1016/j.scitotenv.2018.11.158 (DOI)000458630100088 ()30453266 (PubMedID)2-s2.0-85056696758 (Scopus ID)
Funder
Knowledge Foundation, 20150084
Note

Funding Agency:

Örebro University

Available from: 2019-01-28 Created: 2019-01-28 Last updated: 2019-06-18Bibliographically approved
Kharlyngdoh, J. B., Pradhan, A. & Olsson, P.-E. (2018). Androgen receptor modulation following combination exposure to brominated flame-retardants. Scientific Reports, 8(1), Article ID 4843.
Open this publication in new window or tab >>Androgen receptor modulation following combination exposure to brominated flame-retardants
2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 4843Article in journal (Refereed) Published
Abstract [en]

Endocrine disrupting compounds can interfere with androgen receptor (AR) signaling and disrupt steroidogenesis leading to reproductive failure. The brominated flame-retardant (BFR) 1, 2-dibromo-4-(1, 2-dibromoethyl) cyclohexane (TBECH), is an agonist to human, chicken and zebrafish AR. Recently another group of alternative BFRs, allyl 2, 4, 6-tribromophenyl ether (ATE), and 2, 3-dibromopropyl 2, 4, 6-tribromophenyl ether (DPTE) along with its metabolite 2-bromoallyl 2, 4, 6-tribromophenyl ether (BATE) were identified as potent human AR antagonists. These alternative BFRs are present in the environment. The aim of the present study was to determine the effect of mixed exposures to the AR agonist and the AR antagonists at environmentally relevant concentrations. In vitro reporter luciferase assay showed that the AR antagonists, when present at concentration higher than TBECH, were able to inhibit TBECH-mediated AR activity. These AR antagonists also promoted AR nuclear translocation. In vitro gene expression analysis in the non-tumorigenic human prostate epithelial cell RWPE1 showed that TBECH induced AR target genes whereas DPTE repressed these genes. Further analysis of steroidogenic genes showed that TBECH up-regulated most of the genes while DPTE down-regulated the same genes. The results indicate that when TBECH and DPTE are present together they will antagonize each other, thereby reducing their individual effects.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-66052 (URN)10.1038/s41598-018-23181-0 (DOI)000427688100036 ()29556062 (PubMedID)2-s2.0-85044191096 (Scopus ID)
Funder
Knowledge Foundation
Note

Funding Agency:

Örebro University

Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-08-20Bibliographically approved
Pradhan, A., Olsson, P.-E. & Jass, J. (2018). Di(2-ethylhexyl) phthalate and diethyl phthalate disrupt lipid metabolism, reduce fecundity and shortens lifespan of Caenorhabditis elegans. Chemosphere, 190, 375-382
Open this publication in new window or tab >>Di(2-ethylhexyl) phthalate and diethyl phthalate disrupt lipid metabolism, reduce fecundity and shortens lifespan of Caenorhabditis elegans
2018 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 190, p. 375-382Article in journal (Refereed) Published
Abstract [en]

The widespread use of phthalates is of major concern as they have adverse effects on many different physiological functions, including reproduction, metabolism and cell differentiation. The aim of this study was to compare the toxicity of the widely-used di (2-ethydlhexyl) phthalate (DEHP) with its substitute, diethyl phthalate (DEP). We analyzed the toxicity of these two phthalates using Caenorhabditis elegans as a model system. Gene expression analysis following exposure during the L1 to young adult stage showed that DEHP and DEP alter the expression of genes involved in lipid metabolism and stress response. Genes associated with lipid metabolism, including fasn-1, pod-2, fat-5, acs-6 and sbp-1, and vitellogenin were upregulated. Among the stress response genes, ced-1 wah-1, daf-21 and gst-4 were upregulated, while cd-1, cdf-2 and the heat shock proteins (hsp-16.1, hsp-16.48 and sip-1) were down regulated. Lipid staining revealed that DEHP significantly increased lipid content following 1 mu M exposure, however, DEP required 10 mu M exposure to elicit an effect. Both DEHP and DEP reduced the fecundity at 1 mu M concentration. Lifespan analysis indicated that DEHP and DEP reduced the average lifespan from 14 days in unexposed worms to 13 and 12 days, respectively. Expression of lifespan associated genes showed a correlation to shortened lifespan in the exposed groups. As reported previously, our data also indicates that the banned DEHP is toxic to C. elegans, however its substitute DEP has not been previously tested in this model organism and our data revealed that DEP is equally potent as DEHP in regulating C. elegans physiological functions.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Plasticizer, Metabolism, Reproduction, Toxicity, Longevity
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-62890 (URN)10.1016/j.chemosphere.2017.09.123 (DOI)000414881600041 ()29020644 (PubMedID)2-s2.0-85030660035 (Scopus ID)
Funder
Swedish Research Council, 201504600Knowledge Foundation, 20140180 20150084
Available from: 2017-12-01 Created: 2017-12-01 Last updated: 2018-01-12Bibliographically approved
Pradhan, A. & Olsson, P.-E. (2018). Germ cell depletion in zebrafish leads to incomplete masculinization of the brain. General and Comparative Endocrinology, 265(SI), 15-21
Open this publication in new window or tab >>Germ cell depletion in zebrafish leads to incomplete masculinization of the brain
2018 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 265, no SI, p. 15-21Article in journal (Refereed) Published
Abstract [en]

Zebrafish sex differentiation is under the control of multiple genes, but also relies on germ cell number for gonadal development. Morpholino and chemical mediated germ cell depletion leads to sterile male development in zebrafish. In this study we produced sterile males, using a dead end gene morpholino, to determine gonadal-brain interactions. Germ cell depletion following dnd inhibition downregulated the germ cell markers, vasa and ziwi, and later the larvae developed as sterile males. Despite lacking proper testis, the gonadal 11-ketotestosterone (11-KT) and estradiol (E2) levels of sterile males were similar to wild type males. Qualitative analysis of sexual behavior of sterile males demonstrated that they behaved like wild type males. Furthermore, we observed that brain 11-KT and E2 levels in sterile males remained the same as in the wild type males. In female brain, 11-KT was lower in comparison to wild type males and sterile males, while E2 was higher when compared to wild type males. qRT-PCR analysis revealed that the liver transcript profile of sterile adult males was similar to wild type males while the brain transcript profile was similar to wild type females. The results demonstrate that proper testis development may not be a prerequisite for male brain development in zebrafish but that it may be needed to fully masculinize the brain.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Dimorphism, Gonads, Reproduction, Sex differentiation, Steroid hormone
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-68509 (URN)10.1016/j.ygcen.2018.02.001 (DOI)000442712600003 ()29408375 (PubMedID)2-s2.0-85044373533 (Scopus ID)
Funder
Swedish Research Council
Note

Funding Agency:

Örebro University 

Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-09-06Bibliographically approved
Saju, J. M., Hossain, M. S., Liew, W. C., Pradhan, A., Thevasagayam, N. M., Tan, L. S., . . . Orban, L. (2018). Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish. Cell reports, 25(12), 3252-3261
Open this publication in new window or tab >>Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish
Show others...
2018 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 25, no 12, p. 3252-3261Article in journal (Refereed) Published
Abstract [en]

Heat shock factors (Hsfs) are transcription factors that regulate responses to heat shock and other environmental stimuli. Four heat shock factors (Hsf1-4) have been characterized from vertebrates to date. In addition to stress response, they also play important roles in development and gametogenesis. Here, we study the fifth member of heat shock factor family, Hsf5, using zebrafish as a model organism. Mutant hsf5(-/-) males, generated by CRISPR/Cas9 technique, were infertile with drastically reduced sperm count, increased sperm head size, and abnormal tail architecture, whereas females remained fertile. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis as suggested by the accumulation of cells in the leptotene and zygotene-pachytene stages and increased apoptosis in post-meiotic cells. hsf5(-/-) mutants show gonadal misregulation of a substantial number of genes with roles in cell cycle, apoptosis, protein modifications, and signal transduction, indicating an important role of Hsf5 in early stages of spermatogenesis.

Place, publisher, year, edition, pages
Cell Press, 2018
National Category
Cell Biology
Identifiers
urn:nbn:se:oru:diva-71238 (URN)10.1016/j.celrep.2018.11.090 (DOI)000453826600003 ()30566854 (PubMedID)2-s2.0-85058181011 (Scopus ID)
Funder
Knowledge Foundation
Note

Funding Agencies:

National Research Foundation, Prime Minister's Office, Singapore under its Competitive Research Programme  NRF-CRP7-2010-001 

National Research, Development and Innovation Office of Hungary through its Frontline Research Grant  KKP 126764 

Temasek Life Sciences Laboratory  

Örebro University 

Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-01-09Bibliographically approved
Saju, J. M., Hossain, M. S., Liew, W. C., Pradhan, A., Thevasagayam, N. M., Tan, L. S., . . . Orbán, L. (2018). Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish. Cell reports, 25(12), 3252-3261
Open this publication in new window or tab >>Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish
Show others...
2018 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 25, no 12, p. 3252-3261Article in journal (Refereed) Published
Abstract [en]

Heat shock factors (Hsfs) are transcription factors that regulate responses to heat shock and other environmental stimuli. Four heat shock factors (Hsf1-4) have been characterized from vertebrates to date. In addition to stress response, they also play important roles in development and gametogenesis. Here, we study the fifth member of heat shock factor family, Hsf5, using zebrafish as a model organism. Mutant hsf5(-/-) males, generated by CRISPR/Cas9 technique, were infertile with drastically reduced sperm count, increased sperm head size, and abnormal tail architecture, whereas females remained fertile. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis as suggested by the accumulation of cells in the leptotene and zygotene-pachytene stages and increased apoptosis in post-meiotic cells. hsf5(-/-) mutants show gonadal misregulation of a substantial number of genes with roles in cell cycle, apoptosis, protein modifications, and signal transduction, indicating an important role of Hsf5 in early stages of spermatogenesis.

Place, publisher, year, edition, pages
Cell Press, 2018
National Category
Developmental Biology
Identifiers
urn:nbn:se:oru:diva-80143 (URN)10.1016/j.celrep.2018.11.090 (DOI)000453826600003 ()30566854 (PubMedID)2-s2.0-85058181011 (Scopus ID)
Funder
Knowledge Foundation
Note

Funding Agencies:

National Research Foundation, Prime Minister's Office, Singapore under its Competitive Research Programme  NRF-CRP7-2010-001

National Research, Development and Innovation Office of Hungary through its Frontline Research Grant  KKP 126764

Temasek Life Sciences Laboratory  

Örebro University 

Available from: 2020-02-21 Created: 2020-02-21 Last updated: 2020-03-17Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-3302-7106

Search in DiVA

Show all publications