Transcriptomics profiling and steroid production in mummichog (Fundulus heteroclitus) testes after treatment with 5α-dihydrotestosterone

Feswick, April; Ings, Jennifer S.; Doyle, Meghan A.; Bosker, Thijs; Munkittrick, Kelly R.; Martyniuk, Christopher J.

doi:10.1016/j.ygcen.2014.01.003

Cited by 19 publications

(11 citation statements)

References 73 publications

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“…This agrees with other work done with male mummichog exposed to 5 μg/L and 50 μg/L waterborne DHT, where no impact on StAR expression was observed (Feswick et al, 2014). However, injection of the physiological androgen 11KT into Atlantic cod (Gadus morhua) caused a dose-dependent response in StAR expression.…”

Section: Fig 3 Mean (±1se) Gonadal In Vitro Production (Ng/mg/h) Ofsupporting

confidence: 91%

Effects of model aromatizable (17α-methyltestosterone) and non-aromatizable (5α-dihydrotestosterone) androgens on the adult mummichog (Fundulus heteroclitus) in a short-term reproductive endocrine bioassay

Rutherford

Lister

Hewitt

et al. 2015

Comparative Biochemistry and Physiology Part C: Toxicology &

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Section: Fig 3 Mean (±1se) Gonadal In Vitro Production (Ng/mg/h) Ofsupporting

confidence: 91%

Effects of model aromatizable (17α-methyltestosterone) and non-aromatizable (5α-dihydrotestosterone) androgens on the adult mummichog (Fundulus heteroclitus) in a short-term reproductive endocrine bioassay

Rutherford

Lister

Hewitt

et al. 2015

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…Subsequently, the microarray data were analyzed as described previously (Feswick et al, 2014; Ornostay et al, 2016). A vast number of differentially expressed probes in the distal colon of C57 vs. b1/2-ARs KO chimera mice were observed ( N = 4,072, P < 0.05).…”

Section: Resultsmentioning

confidence: 99%

“…RNA concentrations were determined using the NanoDrop-2000 spectrophotometer (Thermo Scientific). Microarray hybridizations were performed according to the One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling kit (Agilent V6.5, May 2010) and 10 ng total RNA per sample was used for labeling and hybridization as per our previous protocol (Feswick et al, 2014; Ornostay et al, 2016). Microarrays were scanned at 5 μm with the Agilent G2505 C Microarray Scanner, and Agilent Feature Extraction Software (v. 10.1.1.1) was used to extract raw signal intensities from microarray images.…”

Section: Methodsmentioning

confidence: 99%

Shifts in the Gut Microbiota Composition Due to Depleted Bone Marrow Beta Adrenergic Signaling Are Associated with Suppressed Inflammatory Transcriptional Networks in the Mouse Colon

et al. 2017

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The brain-gut axis plays a critical role in the regulation of different diseases, many of which are characterized by sympathetic dysregulation. However, a direct link between sympathetic dysregulation and gut dysbiosis remains to be illustrated. Bone marrow (BM)-derived immune cells continuously interact with the gut microbiota to maintain homeostasis in the host. Their function is largely dependent upon the sympathetic nervous system acting via adrenergic receptors present on the BM immune cells. In this study, we utilized a novel chimera mouse that lacks the expression of BM beta1/2 adrenergic receptors (b1/2-ARs) to investigate the role of the sympathetic drive to the BM in gut and microbiota homeostasis. Fecal analyses demonstrated a shift from a dominance of Firmicutes to Bacteroidetes phylum in the b1/2-ARs KO chimera, resulting in a reduction in Firmicutes/Bacteroidetes ratio. Meanwhile, a significant reduction in Proteobacteria phylum was determined. No changes in the abundance of acetate-, butyrate-, and lactate-producing bacteria, and colon pathology were observed in the b1/2-ARs KO chimera. Transcriptomic profiling in colon identified Killer Cell Lectin-Like Receptor Subfamily D, Member 1 (Klrd1), Membrane-Spanning 4-Domains Subfamily A Member 4A (Ms4a4b), and Casein Kinase 2 Alpha Prime Polypeptide (Csnk2a2) as main transcripts associated with the microbiota shifts in the b1/2-ARs KO chimera. Suppression of leukocyte-related transcriptome networks (i.e., function, differentiation, migration), classical compliment pathway, and networks associated with intestinal function, barrier integrity, and excretion was also observed in the colon of the KO chimera. Moreover, reduced expression of transcriptional networks related to intestinal diseases (i.e., ileitis, enteritis, inflammatory lesions, and stress) was noted. The observed suppressed transcriptome networks were associated with a reduction in NK cells, macrophages, and CD4+ T cells in the b1/2-ARs KO chimera colon. Thus, sympathetic regulation of BM-derived immune cells plays a significant role in modifying inflammatory networks in the colon and the gut microbiota composition. To our knowledge, this study is the first to suggest a key role of BM b1/2-ARs signaling in host-microbiota interactions, and reveals specific molecular mechanisms that may lead to generation of novel anti-inflammatory treatments for many immune and autonomic diseases as well as gut dysbiosis across the board.

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“…RNA concentrations were determined using the NanoDrop-2000 spectrophotometer (Thermo Scientific). Microarray hybridizations were performed according to the One-Color Microarray-Based Gene Expression Analysis Low Input Quick Amp Labeling kit (Agilent V6.5, May 2010) and 50 ng total RNA/sample was used for labeling and hybridization, as per our previous methods (6,22). Microarrays were scanned at 5 m with the Agilent G2505C Microarray Scanner and Agilent Feature Extraction Software (v. 10.1.1.1) was used to extract raw signal intensities from microarray images.…”

Section: Methodsmentioning

confidence: 99%

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

Ahmari

Schmidt

Krane

et al. 2016

Physiological Genomics

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Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure. Physiol Genomics 48: 526 -536, 2016. First published May 27, 2016 doi:10.1152/physiolgenomics.00039.2016 is a prevalent condition with complex etiology and pathophysiology. Evidence exists of significant communication between the nervous system and the immune system (IS), and there appears to be a direct role for inflammatory bone marrow (BM) cells in the pathophysiology of hypertension. However, the molecular and neural mechanisms underlying this interaction have not been characterized. Here, we transplanted whole BM cells from the beta 1 and 2 adrenergic receptor (AdrB1 tm1Bkk AdrB2 tm1Bkk /J) knockout (KO) mice into near lethally irradiated C57BL/6J mice to generate a BM AdrB1.B2 KO chimera. This allowed us to evaluate the role of the BM beta 1 and beta 2 adrenergic receptors in mediating BM IS homeostasis and regulating blood pressure (BP) in an otherwise intact physiological setting. Fluorescence-activated cell sorting demonstrated that a decrease in systolic and mean BP in the AdrB1.B2 KO chimera is associated with a decrease in circulating inflammatory T cells, macrophage/monocytes, and neutrophils. Transcriptomics in the BM identified 7,419 differentially expressed transcripts between the C57 and AdrB1.B2 KO chimera. Pathway analysis revealed differentially expressed transcripts related to several cell processes in the BM of C57 compared with AdrB1.B2 KO chimera, including processes related to immunity (e.g., T-cell activation, T-cell recruitment, cytokine production, leukocyte migration and function), the cardiovascular system (e.g., blood vessel development, peripheral nerve blood flow), and the brain (e.g., central nervous system development, neurite development) among others. This study generates new insight into the molecular events that underlie the interaction between the sympathetic drive and IS in modulation of BP. adrenergic receptors; immune system; bone marrow; chimera; sympathetic drive DYNAMIC INTERPLAY BETWEEN the immune system (IS) and the central nervous system (CNS) exists for physiological homeostasis. The autonomic arm of the CNS, specifically the sympathetic nervous system (SNS), contributes to the diurnal function of the IS by modulating the development and release of bone marrow (BM) hematopoietic cells into circulation via the activation of beta adrenergic receptors expressed by these cells (17,18,25). Activation of the BM beta 1 and 2 adrenergic receptors, in particular, has been shown to modulate the levels of different immune cells in circulation, with inflammatory cells predominantly released during the highest activity period [i.e., night time in rodents and day time in humans (5, 9, 17, 18, 25)], an evolutionary mechanism developed to prime the system for warding off infection, should the need arise. On the other hand, the reciprocal action of an activated IS on the CNS has also been suggested, with significant evid...

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Transcriptomics profiling and steroid production in mummichog (Fundulus heteroclitus) testes after treatment with 5α-dihydrotestosterone

Cited by 19 publications

References 73 publications

Effects of model aromatizable (17α-methyltestosterone) and non-aromatizable (5α-dihydrotestosterone) androgens on the adult mummichog (Fundulus heteroclitus) in a short-term reproductive endocrine bioassay

Effects of model aromatizable (17α-methyltestosterone) and non-aromatizable (5α-dihydrotestosterone) androgens on the adult mummichog (Fundulus heteroclitus) in a short-term reproductive endocrine bioassay

Shifts in the Gut Microbiota Composition Due to Depleted Bone Marrow Beta Adrenergic Signaling Are Associated with Suppressed Inflammatory Transcriptional Networks in the Mouse Colon

Loss of bone marrow adrenergic beta 1 and 2 receptors modifies transcriptional networks, reduces circulating inflammatory factors, and regulates blood pressure

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