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Article ; Online: In vitro antiandrogenic effects of the herbicide linuron and its metabolites.

Ma, Yanying / Pedersen, Mikael / Vinggaard, Anne Marie

2023 Volume 349, Page(s) 140773

Abstract: Although the herbicide linuron is banned for use in the EU due to its reproductive and developmental toxicity, it can still be found in randomly sampled foods grown in and outside the EU. It is not clear if metabolites of linuron can contribute to the ... ...

Abstract	Although the herbicide linuron is banned for use in the EU due to its reproductive and developmental toxicity, it can still be found in randomly sampled foods grown in and outside the EU. It is not clear if metabolites of linuron can contribute to the endocrine disrupting effects following exposure to the parent compound. To address this gap, we analysed linuron and the metabolites 1-(3,4-dichlorophenyl) urea (DCU), 3,4-dichloroaniline (DCA) and 1-(3,4-dichlorophenyl)-3-methoxyurea (DCXU) for androgen receptor (AR) activities and effects on steroidogenesis. Generally, linuron and the metabolites showed qualitatively similar antiandrogenic profiles, but potencies varied. All compounds were AR antagonists, with linuron showing highest potency (IC
MeSH term(s)	Linuron/toxicity ; Herbicides/toxicity ; Androgens ; Androgen Antagonists/toxicity ; Testosterone
Chemical Substances	Linuron (01XP1SU59O) ; Herbicides ; Androgens ; Androgen Antagonists ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2023-11-22
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.2023.140773
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Article ; Online: Key bacterial taxa determine longitudinal dynamics of aromatic amino acid catabolism in infants' gut.

Laursen, Martin F / Sinha, Anurag K / Pedersen, Mikael / Roager, Henrik M

Gut microbes

2023 Volume 15, Issue 1, Page(s) 2221426

Abstract: The development of the gut microbiota in early life is linked to metabolic, neuronal, and immunological development. Recent studies have shown that bacterial production of short-chain fatty acids (SCFAs) and aromatic amino acid (AAA) catabolites in the ... ...

Abstract	The development of the gut microbiota in early life is linked to metabolic, neuronal, and immunological development. Recent studies have shown that bacterial production of short-chain fatty acids (SCFAs) and aromatic amino acid (AAA) catabolites in the gut can mediate host-microbe interactions. However, the dynamics of these microbiota-derived metabolites and the key bacterial taxa producing AAA catabolites during infancy are largely unknown. Here, we investigated the longitudinal dynamics of the microbiota and microbiota-derived SCFAs and AAA catabolites in more than 200 fecal samples from 25 healthy breast- or mixed-fed Danish infants during the first 6 months of life. We found that the gut microbiota composition and metabolism were highly individual but showed significant development over time. SCFAs and specific groups of AAA catabolites showed distinct temporal abundance patterns. Furthermore, we identified bacterial taxa responsible for the generation of AAA catabolites by associating the dynamics of gut microbial taxa and AAA catabolites and subsequently validating these associations in vitro by cultivation of strains representing the associated taxa. In addition to specific
MeSH term(s)	Humans ; Infant ; Gastrointestinal Microbiome/physiology ; Bacteria/genetics ; Bacteria/metabolism ; Fatty Acids, Volatile/metabolism ; Propionates/metabolism ; Feces/microbiology ; Amino Acids, Aromatic/analysis ; Amino Acids, Aromatic/metabolism
Chemical Substances	Fatty Acids, Volatile ; Propionates ; Amino Acids, Aromatic
Language	English
Publishing date	2023-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2023.2221426
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Article ; Online: Simultaneous determination of heterocyclic aromatic amines and N-nitrosamines in fried bacon cubes and slices using LC-(ESI/APCI)-MS/MS.

Niklas, Agnieszka Anna / Pedersen, Mikael / Christensen, Tue / Duedahl-Olesen, Lene

Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment

2023 Volume 40, Issue 4, Page(s) 493–507

Abstract: Bacon manufacturing involves several processing steps including nitrite curing, followed by cooking processes, typically frying. During these processes, harmful processing contaminants such as N-nitrosamines (NAs) and heterocyclic aromatic amines (HAAs) ... ...

Abstract	Bacon manufacturing involves several processing steps including nitrite curing, followed by cooking processes, typically frying. During these processes, harmful processing contaminants such as N-nitrosamines (NAs) and heterocyclic aromatic amines (HAAs) can be formed. Consequently, we developed and validated a multi-class method for quantification of the most frequently reported HAAs and NAs in fried bacon. Satisfactory repeatability and reproducibility with limits of quantification between 0.1 and 0.5 ng g
MeSH term(s)	Tandem Mass Spectrometry/methods ; Pork Meat/analysis ; Reproducibility of Results ; Nitrosamines/analysis ; Amines
Chemical Substances	Nitrosamines ; Amines
Language	English
Publishing date	2023-03-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2462951-0
ISSN	1944-0057 ; 1944-0049
ISSN (online)	1944-0057
ISSN	1944-0049
DOI	10.1080/19440049.2023.2185082
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Article ; Online: Analysis of veterinary drug- and pesticide residues in pig muscle by LC-QTOF-MS

Pedersen, Mikael / Hakme, Elena / Ninga, Ederina / Frandsen, Henrik L.

Food Control. 2023 June, v. 148 p.109656-

2023

Abstract: A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for screening, quantification and identification of veterinary drugs (antibiotics, nonsteroidal anti-inflammatory drugs, anthelmintics, coccidiostatics and tranquilizers) and ... ...

Abstract	A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for screening, quantification and identification of veterinary drugs (antibiotics, nonsteroidal anti-inflammatory drugs, anthelmintics, coccidiostatics and tranquilizers) and pesticide residues was validated in pig (porcine) muscle. Tissues were extracted with acidic methanol/water with EDTA, followed by dispersive solid phase extraction to remove unpolar interferences. Before analysis the extracts were centrifuged at high speed (12.000 g). A MaXis Q-TOF mass spectrometer equipped with an electrospray ion source was operated in positive mode. In the same analysis full scan acquisition with a mass range of 80-1100 amu and broadband collision induced dissociation (bbCID) acquisition were applied for screening and identification. Identification criteria for screening were established for detector response (intensity and area), mass accuracy, isotopic pattern, retentiontime and qualifier ions. The screening method was validated for 65 veterinary drug residues and 97 pesticide residues and the stability of selected veterinary drugs in pig muscle was evaluated over a six month period.
Keywords	anthelmintics ; dissociation ; food safety ; liquid chromatography ; mass spectrometry ; methanol ; muscles ; pesticides ; solid phase extraction ; spectrometers ; swine ; veterinary drugs ; Liquid chromatography-high resolution mass spectrometry (LC-HRMS) ; Stability testing
Language	English
Dates of publication	2023-06
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	1027805-9
ISSN	0956-7135
ISSN	0956-7135
DOI	10.1016/j.foodcont.2023.109656
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Article ; Online: Simultaneous determination of heterocyclic aromatic amines and N-nitrosamines in fried bacon cubes and slices using LC-(ESI/APCI)-MS/MS

Niklas, Agnieszka Anna / Pedersen, Mikael / Christensen, Tue / Duedahl-Olesen, Lene

Food Additives & Contaminants: Part A. 2023 Apr. 3, v. 40, no. 4 p.493-507

2023

Abstract	Bacon manufacturing involves several processing steps including nitrite curing, followed by cooking processes, typically frying. During these processes, harmful processing contaminants such as N-nitrosamines (NAs) and heterocyclic aromatic amines (HAAs) can be formed. Consequently, we developed and validated a multi-class method for quantification of the most frequently reported HAAs and NAs in fried bacon. Satisfactory repeatability and reproducibility with limits of quantification between 0.1 and 0.5 ng g⁻¹ for most of the compounds were achieved. Quantification in pan-fried bacon cubes and slices revealed generally low levels of individual HAAs (≤1.5 ng g⁻¹), except in ready-to-eat bacon (0.9–2.9 ng g⁻¹). Differences in amounts of individual HAAs were observed in cubes and slices, most likely due to meat thickness. Among volatile NAs (VNAs), only N-nitrosopiperidine (NPIP), N-nitrosopyrolidine (NPYR), and N-nitrosodibutylamine (NDBA) were found at generally low concentrations (≤5 ng g⁻¹). In contrast, non-volatile NAs (NVNAs) were present in all tested samples at considerably higher amounts, for example, N-nitroso-thiazolidine-4-carboxylic acid (NTCA) at 12–77 ng g⁻¹. N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodipropylamine (NDPA) were not detected in any samples. Statistical evaluation and principal component analysis revealed some differences among tested samples. Dietary exposure estimation of the Danish population to HAAs and NAs showed the highest exposure in the teenage group (10–17 years).
Keywords	N-nitrosodimethylamine ; bacon ; dietary exposure ; diethylnitrosamine ; heterocyclic compounds ; nitrites ; pan frying ; principal component analysis ; ready-to-eat foods ; Processing contaminants ; multi-class method ; fried bacon ; liquid chromatography-tandem mass spectrometry
Language	English
Dates of publication	2023-0403
Size	p. 493-507.
Publishing place	Taylor & Francis
Document type	Article ; Online
ZDB-ID	2462951-0
ISSN	1944-0057 ; 1944-0049
ISSN (online)	1944-0057
ISSN	1944-0049
DOI	10.1080/19440049.2023.2185082
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Article ; Online: An engineered Escherichia coli Nissle 1917 increase the production of indole lactic acid in the gut.

Dimopoulou, Chrysoula / Bongers, Mareike / Pedersen, Mikael / Bahl, Martin I / Sommer, Morten O A / Laursen, Martin F / Licht, Tine R

FEMS microbiology letters

2023 Volume 370

Abstract: The expanding knowledge of the health impacts of the metabolic activities of the gut microbiota reinforces the current interest in engineered probiotics. Tryptophan metabolites, in particular indole lactic acid (ILA), are attractive candidates as ... ...

Abstract	The expanding knowledge of the health impacts of the metabolic activities of the gut microbiota reinforces the current interest in engineered probiotics. Tryptophan metabolites, in particular indole lactic acid (ILA), are attractive candidates as potential therapeutic agents. ILA is a promising compound with multiple beneficial effects, including amelioration colitis in rodent models of necrotizing enterocolitis, as well as improved infant immune system maturation. In this work, we engineered and characterized in vitro and in vivo an Escherichia coli Nissle 1917 strain that produces ILA. The 2-step metabolic pathway comprises aminotransferases native of E. coli and a dehydrogenase introduced from Bifidobacterium longum subspecies infantis. Our results show a robust engineered probiotic that produces 73.4 ± 47.2 nmol and 149 ± 123.6 nmol of ILA per gram of fecal and cecal matter, respectively, three days after colonization in a mouse model. In addition, hereby is reported an engineered-probiotic-related increase of ILA in the systemic circulation of the treated mice. This strain serves as proof of concept for the transfer of capacity to produce ILA in vivo and as ILA emerges as a potent microbial metabolite against gastrointestinal inflammation, further development of this strain offers efficient options for ILA-focused therapeutic interventions in situ.
MeSH term(s)	Mice ; Animals ; Escherichia coli/genetics ; Colitis/therapy ; Colitis/microbiology ; Feces/microbiology ; Cecum ; Indoles ; Probiotics
Chemical Substances	Indoles
Language	English
Publishing date	2023-04-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1093/femsle/fnad027
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Article ; Online: PPARγ antagonists induce aromatase transcription in adipose tissue cultures.

Ardenkjær-Skinnerup, Jacob / Saar, Daniel / Petersen, Patricia S S / Pedersen, Mikael / Svingen, Terje / Kragelund, Birthe B / Hadrup, Niels / Ravn-Haren, Gitte / Emanuelli, Brice / Brown, Kristy A / Vogel, Ulla

Biochemical pharmacology

2024 Volume 222, Page(s) 116095

Abstract: Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens and a key risk factor for hormone receptor-positive breast cancer. In postmenopausal women, estrogens synthesized in adipose tissue promotes the growth of estrogen receptor positive ... ...

Abstract	Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens and a key risk factor for hormone receptor-positive breast cancer. In postmenopausal women, estrogens synthesized in adipose tissue promotes the growth of estrogen receptor positive breast cancers. Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in adipose stromal cells (ASCs) leads to decreased expression of aromatase and differentiation of ASCs into adipocytes. Environmental chemicals can act as antagonists of PPARγ and disrupt its function. This study aimed to test the hypothesis that PPARγ antagonists can promote breast cancer by stimulating aromatase expression in human adipose tissue. Primary cells and explants from human adipose tissue as well as A41hWAT, C3H10T1/2, and H295R cell lines were used to investigate PPARγ antagonist-stimulated effects on adipogenesis, aromatase expression, and estrogen biosynthesis. Selected antagonists inhibited adipocyte differentiation, preventing the adipogenesis-associated downregulation of aromatase. NMR spectroscopy confirmed direct interaction between the potent antagonist DEHPA and PPARγ, inhibiting agonist binding. Short-term exposure of ASCs to PPARγ antagonists upregulated aromatase only in differentiated cells, and a similar effect could be observed in human breast adipose tissue explants. Overexpression of PPARG with or without agonist treatment reduced aromatase expression in ASCs. The data suggest that environmental PPARγ antagonists regulate aromatase expression in adipose tissue through two mechanisms. The first is indirect and involves inhibition of adipogenesis, while the second occurs more acutely.
MeSH term(s)	Female ; Humans ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Aromatase/genetics ; Aromatase/metabolism ; Adipose Tissue/metabolism ; Estrogens/metabolism ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Adipogenesis
Chemical Substances	PPAR gamma ; Aromatase (EC 1.14.14.1) ; Estrogens
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2024.116095
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Article ; Online: Exposure to the phthalate metabolite MEHP impacts survival and growth of human ovarian follicles in vitro.

Panagiotou, Eleftheria Maria / Damdimopoulos, Anastasios / Li, Tianyi / Moussaud-Lamodière, Elisabeth / Pedersen, Mikael / Lebre, Filipa / Pettersson, Karin / Arnelo, Catarina / Papaikonomou, Kiriaki / Alfaro-Moreno, Ernesto / Lindskog, Cecilia / Svingen, Terje / Damdimopoulou, Pauliina

Toxicology

2024 , Page(s) 153815

Abstract: Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between ... ...

Abstract	Phthalates are found in everyday items like plastics and personal care products. There is an increasing concern that continuous exposure can adversely affect female fertility. However, experimental data are lacking to establish causal links between exposure and disease in humans. To address this gap, we tested the effects of a common phthalate metabolite, mono-(2-ethylhexyl) phthalate (MEHP), on adult human ovaries in vitro using an epidemiologically determined human-relevant concentration range (2.05nM - 20.51mM). Histomorphological assessments, steroid and cytokine measurements were performed on human ovarian tissue exposed to MEHP for 7 days in vitro. Cell viability and gene expression profile were investigated following 7 days of MEHP exposure using the human granulosa cancer cell lines (KGN, COV434), the germline tumor cell line (PA-1), and human ovarian primary cells. Selected differentially expressed genes (DEGs) were validated by RT-qPCR and immunofluorescence in human ovarian tissue. MEHP exposure reduced follicular growth (20.51nM) and increased follicular degeneration (20.51mM) in ovarian tissue, while not affecting steroid and cytokine production. Out of the 691 unique DEGs identified across all the cell types and concentrations, CSRP2 involved in cytoskeleton organization and YWHAE as well as CTNNB1 involved in the Hippo pathway, were chosen for further validation. CSRP2 was upregulated and CTNNB1 downregulated in both ovarian tissue and cells, whereas YWHAE was downregulated in cells only. In summary, one-week MEHP exposure of human ovarian tissue can perturb the development and survival of human follicles through mechanisms likely involving dysregulation of cytoskeleton organization and Hippo pathway.
Language	English
Publishing date	2024-04-27
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	184557-3
ISSN	1879-3185 ; 0300-483X
ISSN (online)	1879-3185
ISSN	0300-483X
DOI	10.1016/j.tox.2024.153815
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Article ; Online: Atypical TGF-β signaling controls neuronal guidance in

Baltaci, Oguzhan / Pedersen, Mikael Egebjerg / Sherry, Tessa / Handley, Ava / Snieckute, Goda / Cao, Wei / Haas, Matilda / Archer, Stuart / Pocock, Roger

iScience

2022 Volume 25, Issue 2, Page(s) 103791

Abstract: Coordinated expression of cell adhesion and signaling molecules is crucial for brain development. Here, we report that ... ...

Abstract	Coordinated expression of cell adhesion and signaling molecules is crucial for brain development. Here, we report that the
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.103791
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Article ; Online: Exposure to the pesticides linuron, dimethomorph and imazalil alters steroid hormone profiles and gene expression in developing rat ovaries.

Boberg, Julie / Johansson, Hanna K L / Franssen, Delphine / Draskau, Monica Kam / Christiansen, Sofie / Cramer, Johannah / Pedersen, Mikael / Parent, Anne-Simone / Svingen, Terje

Toxicology letters

2022 Volume 373, Page(s) 114–122

Abstract: Inhibition of androgen signaling during critical stages of ovary development can disrupt folliculogenesis with potential consequences for reproductive function later in life. Many environmental chemicals can inhibit the androgen signaling pathway, which ... ...

Abstract	Inhibition of androgen signaling during critical stages of ovary development can disrupt folliculogenesis with potential consequences for reproductive function later in life. Many environmental chemicals can inhibit the androgen signaling pathway, which raises the question if developmental exposure to anti-androgenic chemicals can negatively impact female fertility. Here, we report on altered reproductive hormone profiles in prepubertal female rats following developmental exposure to three pesticides with anti-androgenic potential: linuron (25 and 50 mg/kg bw/d), dimethomorph (60 and 180 mg/kg bw/d) and imazalil (8 and 24 mg/kg bw/d). Dams were orally exposed from gestational day 7 (dimethomorph and imazalil) or 13 (linuron) until birth, then until end of dosing at early postnatal life. Linuron and dimethomorph induced dose-related reductions to plasma corticosterone levels, whereas imazalil mainly suppressed gonadotropin levels. In the ovaries, expression levels of target genes were affected by linuron and dimethomorph, suggesting impaired follicle growth. Based on our results, we propose that anti-androgenic chemicals can negatively impact female reproductive development. This highlights a need to integrate data from all levels of the hypothalamic-pituitary-gonadal axis, as well as the hypothalamic-pituitary-adrenal axis, when investigating the potential impact of endocrine disruptors on female reproductive development and function.
Language	English
Publishing date	2022-11-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	433788-8
ISSN	1879-3169 ; 0378-4274
ISSN (online)	1879-3169
ISSN	0378-4274
DOI	10.1016/j.toxlet.2022.11.010
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