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Article ; Online: DNA methylation reprogramming in medaka fish, a promising animal model for environmental epigenetics research.

Wang, Xuegeng / Bhandari, Ramji K

2020 Volume 6, Issue 1, Page(s) dvaa008

Abstract: DNA methylation is a major epigenetic modification that undergoes dramatic changes in two epigenetic reprogramming windows during development: first in preimplantation embryos and second in primordial germ cell (PGC) specification. In both windows, DNA ... ...

Abstract	DNA methylation is a major epigenetic modification that undergoes dramatic changes in two epigenetic reprogramming windows during development: first in preimplantation embryos and second in primordial germ cell (PGC) specification. In both windows, DNA methylation patterns are reprogrammed genome-wide, and the majority of inherited methylation marks are erased, generating cells with broad developmental potential. Recent studies reported that the reprogramming of genome methylation in medaka is similar to human and mouse, suggesting that medaka may serve as a suitable biomedical model for comparative studies focused on the epigenetic and transgenerational inheritance of phenotypic traits. In this mini review, we will discuss how somatic and germ cells in post-fertilization stage embryos are epigenetically reprogrammed in mammals and fishes with a particular focus on DNA methylation dynamics.
Language	English
Publishing date	2020-07-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2831217-X
ISSN	2058-5888 ; 2058-5888
ISSN (online)	2058-5888
ISSN	2058-5888
DOI	10.1093/eep/dvaa008
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Medaka as a model for studying environmentally induced epigenetic transgenerational inheritance of phenotypes.

Bhandari, Ramji K

Environmental epigenetics

2016 Volume 2, Issue 1, Page(s) dvv010

Abstract: Ability of environmental stressors to induce transgenerational diseases has been experimentally demonstrated in plants, worms, fish, and mammals, indicating that exposures affect not only human health but also fish and ecosystem health. Small aquarium ... ...

Abstract	Ability of environmental stressors to induce transgenerational diseases has been experimentally demonstrated in plants, worms, fish, and mammals, indicating that exposures affect not only human health but also fish and ecosystem health. Small aquarium fish have been reliable model to study genetic and epigenetic basis of development and disease. Additionally, fish can also provide better, economic opportunity to study transgenerational inheritance of adverse health and epigenetic mechanisms. Molecular mechanisms underlying germ cell development in fish are comparable to those in mammals and humans. This review will provide a short overview of long-term effects of environmental chemical contaminant exposure in various models, associated epigenetic mechanisms, and a perspective on fish as model to study environmentally induced transgenerational inheritance of altered phenotypes.
Language	English
Publishing date	2016-01-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2831217-X
ISSN	2058-5888
ISSN	2058-5888
DOI	10.1093/eep/dvv010
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Article ; Online: Potassium perchlorate effects on primordial germ cells of developing medaka larvae.

Reh, Beh / Wang, Xuegeng / Feng, Yashi / Bhandari, Ramji K

Aquatic toxicology (Amsterdam, Netherlands)

2022 Volume 251, Page(s) 106283

Abstract: Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Exposure of humans to perchlorate can occur in the theater of war and areas adjacent to military ... ...

Abstract	Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Exposure of humans to perchlorate can occur in the theater of war and areas adjacent to military training grounds. A high concentration of perchlorate has been found to affect reproduction in vertebrates, including fish. However, whether environmental concentrations of perchlorate can affect primordial germ cells (PGCs), the founders of sperm and eggs, is not clearly understood. In the present study, we examined the effects of 0, 10, 100, and 1000 μg/L potassium perchlorate exposure on the embryonic development of medaka and their PGCs. Perchlorate exposure delayed hatching time, reduced heartbeat, inhibited migration of PGCs, and increased developmental deformities in the larvae. The 10 and 20 mg/L concentrations of perchlorate were lethal to embryos, whereas vitamin C co-treatment (1 mg/L) completely blocked perchlorate-induced mortality. RNA-seq analysis of isolated PGCs showed a non-linear pattern in expression profiles of differentially altered genes. Significantly upregulated genes were found in PGCs from the 10 and 1000 μg/L groups, whereas the 100 μg/L groups showed the highest number of significantly downregulated genes. Gene ontology analysis predicted differentially expressed genes to be involved in proteolysis, metabolic processes, peptides activity, hydrolase activity, and hormone activity. Among the cellular components, extracellular, intracellular, sarcoplasmic, and 6-phosphofructokinase and membrane-bounded processes were affected. Ingenuity Pathway Analysis of PGC transcriptomes revealed thyroid hormone signaling to be affected by all concentrations of perchlorate. The present results suggested that perchlorate affected the development of medaka larvae and vitamin C was able to ameliorate perchlorate-induced embryo mortality. Additionally, perchlorate altered the global transcriptional network in PGCs in a non-linear fashion suggesting its potential effects on developing germ cells and fertility.
MeSH term(s)	Animals ; Ascorbic Acid/metabolism ; Drinking Water/metabolism ; Female ; Germ Cells/metabolism ; Hormones/metabolism ; Humans ; Hydrolases/metabolism ; Larva ; Male ; Oryzias/genetics ; Perchlorates/metabolism ; Perchlorates/toxicity ; Potassium Compounds ; Semen ; Soil ; Water Pollutants, Chemical/toxicity
Chemical Substances	Drinking Water ; Hormones ; Perchlorates ; Potassium Compounds ; Soil ; Water Pollutants, Chemical ; potassium perchlorate (42255P5X4D) ; Hydrolases (EC 3.-) ; Ascorbic Acid (PQ6CK8PD0R) ; perchlorate (VLA4NZX2P4)
Language	English
Publishing date	2022-08-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	782699-0
ISSN	1879-1514 ; 0166-445X
ISSN (online)	1879-1514
ISSN	0166-445X
DOI	10.1016/j.aquatox.2022.106283
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Article ; Online: Author Correction: Nano-fibre Integrated Microcapsules: A Nano-in-Micro Platform for 3D Cell Culture.

Khanal, Shalil / Bhattarai, Shanta R / Sankar, Jagannathan / Bhandari, Ramji K / Macdonald, Jeffrey M / Bhattarai, Narayan

Scientific reports

2023 Volume 13, Issue 1, Page(s) 1269

Language	English
Publishing date	2023-01-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-28208-9
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Article: Potassium Perchlorate Effects on Primordial Germ Cells of Developing Medaka Larvae

Reh, Beh / Wang, Xuegeng / Feng, Yashi / Bhandari, Ramji K.

Aquatic toxicology. 2022 Aug. 25,

2022

Abstract: Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Human exposure can occur in the theatre of war and areas adjacent to military training grounds. A ... ...

Abstract	Perchlorate is a chemical compound commonly used in military artillery and equipment. It has been detected in drinking water, air, soil, and breast milk. Human exposure can occur in the theatre of war and areas adjacent to military training grounds. A high concentration of perchlorate has been found to affect reproduction in vertebrates, including fish. However, whether environmental concentrations of perchlorate can affect primordial germ cells (PGCs), the founders of sperm and eggs, is not clearly understood. In the present study, we examined the effects of 0, 10, 100, and 1000 μg/L potassium perchlorate exposure on the embryonic development of medaka and larvae and their PGCs. Perchlorate exposure delayed hatching time, reduced heartbeat, inhibited migration of PGCs, and increased developmental deformities in the larvae. The 10 and 20 mg/L concentrations of perchlorate were lethal to embryos, whereas vitamin C co-treatment (1 mg/L) completely blocked perchlorate-induced mortality. RNA-seq analysis of isolated PGCs showed a non-linear pattern in expression profiles of differentially altered genes. Significantly upregulated genes were found in PGCs from the 10 and 1000 μg/L groups, whereas the 100 μg/L groups showed the highest number of significantly downregulated genes. Gene ontology analysis predicted differentially expressed genes to be involved in proteolysis, metabolic processes, peptides activity, hydrolase activity, and hormone activity. Among the cellular components, extracellular, intracellular, sarcoplasmic, and 6-phosphofructokinase and membrane-bounded processes were affected. Ingenuity Pathway Analysis of PGC transcriptomes revealed thyroid hormone signaling to be affected by all concentrations of perchlorate. The present results suggested that perchlorate affected the development of medaka larvae and vitamin C was able to ameliorate perchlorate-induced embryo mortality. Additionally, perchlorate altered the global transcriptional network in PGCs in a non-linear fashion suggesting its potential effects on developing germ cells and fertility.
Keywords	6-phosphofructokinase ; air ; ascorbic acid ; breast milk ; embryogenesis ; embryonic mortality ; equipment ; fish ; gene expression regulation ; gene ontology ; heart rate ; humans ; hydrolases ; mortality ; peptides ; perchlorates ; potassium ; proteolysis ; sequence analysis ; soil ; spermatozoa ; thyroid hormones ; toxicology ; transcription (genetics) ; transcriptome
Language	English
Dates of publication	2022-0825
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	782699-0
ISSN	1879-1514 ; 0166-445X
ISSN (online)	1879-1514
ISSN	0166-445X
DOI	10.1016/j.aquatox.2022.106283
Database	NAL-Catalogue (AGRICOLA)

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Article: Ancestral BPA exposure caused defects in the liver of medaka for four generations

Chakraborty, Sourav / Dissanayake, Manthi / Godwin, Julia / Wang, Xuegeng / Bhandari, Ramji K.

Science of the total environment. 2022 Sept. 23,

2022

Abstract: In addition to lifestyle-induced liver defects, environmental chemicals can induce liver defects in experimental animals due to their direct and acute exposure. It is not clear whether environmental chemical exposures result in the transgenerational ... ...

Abstract	In addition to lifestyle-induced liver defects, environmental chemicals can induce liver defects in experimental animals due to their direct and acute exposure. It is not clear whether environmental chemical exposures result in the transgenerational passage of liver defects in subsequent generations living in an uncontaminated environment. Bisphenol A (BPA), a plasticizer chemical, has been ubiquitous in the environment in the recent decade. Every organism is exposed to this chemical at some point during its lifetime. Literature suggests that direct BPA exposure can result in several metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). Despite the phasing out of BPA from several consumer goods, it is unclear whether ancestral BPA exposure causes liver health problems in the unexposed future generations. Here, we demonstrate an advanced stage of NAFLD in the grandchildren (F2 generation) of medaka fish (Oryzias latipes) due to embryonic BPA exposure in the grandparental generation (F0), which persists for five generations (F4) even in the absence of BPA. The severity of transgenerational NAFLD phenotype included steatosis together with perisinusoidal fibrosis and apoptosis of hepatocytes. Adult females developed more severe histopathological conditions in the liver than males. Genes encoding enzymes involved in lipolytic pathways were significantly decreased. The present results suggest that ancestral BPA exposure can result in transgenerational metabolic diseases that can persist for five generations and that the NAFLD trait is sexually dimorphic. Given that ancestral BPA exposure can lead to altered metabolic health outcomes in the subsequent unexposed generations, the development of the methods and strategies to mitigate the transgenerational onset of metabolic diseases seem imperative to protect future generations.
Keywords	Oryzias latipes ; acute exposure ; adults ; apoptosis ; bisphenol A ; environment ; fatty liver ; fibrosis ; hepatocytes ; histopathology ; liver ; phenotype ; plasticizers ; sexual dimorphism
Language	English
Dates of publication	2022-0923
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2022.159067
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Article ; Online: Developmental abnormalities and epigenetic alterations in medaka (Oryzias latipes) embryos induced by triclosan exposure.

Song, Xiaohong / Wang, Xuegeng / Bhandari, Ramji K

Chemosphere

2020 Volume 261, Page(s) 127613

Abstract: Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various ...

Abstract	Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various species of fish. It is not clearly understood whether TCS exposure causes epigenetic alterations in developing embryos and their germ cells. In the present study, we examined the effects of TCS exposure (0, 50, 100 and, 200 μg/L) on embryonic development and primordial germ cells (PGCs), which are precursors of sperm and eggs, in medaka (Oyzias latipes). Developmental TCS exposure from 8 h post-fertilization through 15 days post-fertilization (dpf) resulted in several developmental abnormalities, including enlarged yolk sac, decreased head trunk angle (HTA), and severe edema in the pericardial region. The male ratio increased in the 100 μg/L TCS exposure group, which was negatively correlated with the expression of cyp19ala (a gene encoding aromatase) and arα (androgen receptor alpha). Developmental 50 μg/L TCS exposure resulted in global hypomethylation in the whole body but not in the isolated PGCs. Expression of the gene encoding DNA methyltransferases (dnmt1 and dnmt3aa) was decreased by 50 μg/L TCS exposure both in the whole body and PGCs. TCS altered the expression of genes encoding enzymes involved in DNA methylation and demethylation in PGCs, suggesting epigenetic effects on germ cells. The present results demonstrate that the embryos exposed to the tested concentrations of TCS develop deformities during the early life stages and that the TCS within this range possesses endocrine disrupting properties potential enough to alter sex ratios of developing embryos.
MeSH term(s)	Animals ; DNA Methylation/drug effects ; Embryo, Nonmammalian/drug effects ; Endocrine Disruptors/pharmacology ; Epigenesis, Genetic/drug effects ; Epigenomics ; Germ Cells/drug effects ; Male ; Oryzias/embryology ; Triclosan/pharmacology ; Triclosan/toxicity ; Water Pollutants, Chemical/toxicity
Chemical Substances	Endocrine Disruptors ; Water Pollutants, Chemical ; Triclosan (4NM5039Y5X)
Language	English
Publishing date	2020-07-13
Publishing country	England
Document type	Journal Article
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2020.127613
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2540: Show issues

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Article ; Online: Distinct expression patterns of seven crucial microRNAs during early embryonic development in medaka (Oryzias latipes).

Wang, Xuegeng / Song, Xiaohong / Bhandari, Ramji K

Gene expression patterns : GEP

2020 Volume 37, Page(s) 119133

Abstract: MicroRNAs (i.e. miRNAs) are small non-coding RNAs that play essential modulation roles in embryonic development in vertebrates. Paternal and maternal miRNAs contribute to the development of post-fertilization embryo and zygotic genome activation. The ... ...

Abstract	MicroRNAs (i.e. miRNAs) are small non-coding RNAs that play essential modulation roles in embryonic development in vertebrates. Paternal and maternal miRNAs contribute to the development of post-fertilization embryo and zygotic genome activation. The pattern of expression and their roles in embryonic development of medaka are not clearly understood. The present study, therefore, examined a temporal expression of seven miRNAs, ola-let-7a, ola-miR-202-3p, ola-miR-126-3p, ola-miR-122, ola-miR-92a, ola-miR-125a-3p and ola-miR-430a in sperm, oocytes, and embryos during early developmental stages. Three unique expression patterns of miRNAs were observed. ola-let7a, ola-miR-202-3p and ola-miR-126-3p showed both paternal and maternal expression, and ola-miR-122, ola-miR-92a, ola-miR-125a-3p showed maternal expression only. The expression of six out of seven miRNAs significantly decreased after maternal-zygotic transition (MZT), whereas ola-miR-430a expression initiated only after MZT. The temporal dynamic expression of these miRNAs suggests their potential roles in early embryogenesis and genome-zygotic activation in medaka.
MeSH term(s)	Animals ; Embryonic Development/genetics ; Female ; Gene Expression Regulation, Developmental ; Male ; MicroRNAs/genetics ; Oocytes/metabolism ; Oryzias/embryology ; Oryzias/genetics ; Spermatozoa/metabolism
Chemical Substances	MicroRNAs
Language	English
Publishing date	2020-08-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2058346-1
ISSN	1872-7298 ; 1567-133X
ISSN (online)	1872-7298
ISSN	1567-133X
DOI	10.1016/j.gep.2020.119133
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Article: Developmental abnormalities and epigenetic alterations in medaka (Oryzias latipes) embryos induced by triclosan exposure

Song, Xiaohong / Wang, Xuegeng / Bhandari, Ramji K

Chemosphere. 2020 Dec., v. 261

2020

Abstract	Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various species of fish. It is not clearly understood whether TCS exposure causes epigenetic alterations in developing embryos and their germ cells. In the present study, we examined the effects of TCS exposure (0, 50, 100 and, 200 μg/L) on embryonic development and primordial germ cells (PGCs), which are precursors of sperm and eggs, in medaka (Oyzias latipes). Developmental TCS exposure from 8 h post-fertilization through 15 days post-fertilization (dpf) resulted in several developmental abnormalities, including enlarged yolk sac, decreased head trunk angle (HTA), and severe edema in the pericardial region. The male ratio increased in the 100 μg/L TCS exposure group, which was negatively correlated with the expression of cyp19ala (a gene encoding aromatase) and arα (androgen receptor alpha). Developmental 50 μg/L TCS exposure resulted in global hypomethylation in the whole body but not in the isolated PGCs. Expression of the gene encoding DNA methyltransferases (dnmt1 and dnmt3aa) was decreased by 50 μg/L TCS exposure both in the whole body and PGCs. TCS altered the expression of genes encoding enzymes involved in DNA methylation and demethylation in PGCs, suggesting epigenetic effects on germ cells. The present results demonstrate that the embryos exposed to the tested concentrations of TCS develop deformities during the early life stages and that the TCS within this range possesses endocrine disrupting properties potential enough to alter sex ratios of developing embryos.
Keywords	DNA ; DNA methylation ; Leptothrium ; Oryzias latipes ; abnormal development ; androgen receptors ; aromatase ; correlation ; demethylation ; developmental stages ; edema ; eggs ; embryogenesis ; environment ; epigenetics ; fish ; gene expression ; genes ; head ; males ; methyltransferases ; pericardium ; products and commodities ; sex ratio ; spermatozoa ; triclosan ; yolk sac
Language	English
Dates of publication	2020-12
Publishing place	Elsevier Ltd
Document type	Article
Note	NAL-light
ZDB-ID	120089-6
ISSN	1879-1298 ; 0045-6535 ; 0366-7111
ISSN (online)	1879-1298
ISSN	0045-6535 ; 0366-7111
DOI	10.1016/j.chemosphere.2020.127613
Database	NAL-Catalogue (AGRICOLA)

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Article: Distinct expression patterns of seven crucial microRNAs during early embryonic development in medaka (Oryzias latipes)

Wang, Xuegeng / Song, Xiaohong / Bhandari, Ramji K

Gene expression patterns. 2020 Sept., v. 37

2020

Abstract	MicroRNAs (i.e. miRNAs) are small non-coding RNAs that play essential modulation roles in embryonic development in vertebrates. Paternal and maternal miRNAs contribute to the development of post-fertilization embryo and zygotic genome activation. The pattern of expression and their roles in embryonic development of medaka are not clearly understood. The present study, therefore, examined a temporal expression of seven miRNAs, ola-let-7a, ola-miR-202-3p, ola-miR-126-3p, ola-miR-122, ola-miR-92a, ola-miR-125a-3p and ola-miR-430a in sperm, oocytes, and embryos during early developmental stages. Three unique expression patterns of miRNAs were observed. ola-let7a, ola-miR-202-3p and ola-miR-126-3p showed both paternal and maternal expression, and ola-miR-122, ola-miR-92a, ola-miR-125a-3p showed maternal expression only. The expression of six out of seven miRNAs significantly decreased after maternal-zygotic transition (MZT), whereas ola-miR-430a expression initiated only after MZT. The temporal dynamic expression of these miRNAs suggests their potential roles in early embryogenesis and genome-zygotic activation in medaka.
Keywords	Oryzias latipes ; developmental stages ; embryogenesis ; genome ; microRNA ; non-coding RNA ; oocytes ; spermatozoa ; vertebrates
Language	English
Dates of publication	2020-09
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2058346-1
ISSN	1872-7298 ; 1567-133X
ISSN (online)	1872-7298
ISSN	1567-133X
DOI	10.1016/j.gep.2020.119133
Database	NAL-Catalogue (AGRICOLA)

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