scholarly journals Sex-dependent dynamics of metabolism in primary mouse hepatocytes

2021 ◽  
Author(s):  
Luise Hochmuth ◽  
Christiane Körner ◽  
Fritzi Ott ◽  
Daniela Volke ◽  
Kaja Blagotinšek Cokan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Sexual Dimorphism ◽  
New Drugs ◽  
Model Systems ◽  
Specific Gene ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Male And Female ◽  
Primary Mouse

AbstractThe liver is one of the most sexually dimorphic organs. The hepatic metabolic pathways that are subject to sexual dimorphism include xenobiotic, amino acid and lipid metabolism. Non-alcoholic fatty liver disease and hepatocellular carcinoma are among diseases with sex-dependent prevalence, progression and outcome. Although male and female livers differ in their abilities to metabolize foreign compounds, including drugs, sex-dependent treatment and pharmacological dynamics are rarely applied in all relevant cases. Therefore, it is important to consider hepatic sexual dimorphism when developing new treatment strategies and to understand the underlying mechanisms in model systems. We isolated primary hepatocytes from male and female C57BL6/N mice and examined the sex-dependent transcriptome, proteome and extracellular metabolome parameters in the course of culturing them for 96 h. The sex-specific gene expression of the general xenobiotic pathway altered and the female-specific expression of Cyp2b13 and Cyp2b9 was significantly reduced during culture. Sex-dependent differences of several signaling pathways increased, including genes related to serotonin and melatonin degradation. Furthermore, the ratios of male and female gene expression were inversed for other pathways, such as amino acid degradation, beta-oxidation, androgen signaling and hepatic steatosis. Because the primary hepatocytes were cultivated without the influence of known regulators of sexual dimorphism, these results suggest currently unknown modulatory mechanisms of sexual dimorphism in vitro. The large sex-dependent differences in the regulation and dynamics of drug metabolism observed during cultivation can have an immense influence on the evaluation of pharmacodynamic processes when conducting initial preclinical trials to investigate potential new drugs.

scholarly journals Role of IME1 expression in regulation of meiosis in Saccharomyces cerevisiae.

1990 ◽  
Vol 10 (12) ◽  
pp. 6103-6113 ◽  
Author(s):  
H E Smith ◽  
S S Su ◽  
L Neigeborn ◽  
S E Driscoll ◽  
A P Mitchell
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Amino Acid ◽  
Specific Gene ◽  
Alpha Cells ◽  
Cell Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Specific Gene Expression ◽  
Gal1 Promoter ◽  
Acid Protein

Two signals are required for meiosis and spore formation in the yeast Saccharomyces cerevisiae: starvation and the MAT products a1 and alpha 2, which determine the a/alpha cell type. These signals lead to increased expression of the IME1 (inducer of meiosis) gene, which is required for sporulation and sporulation-specific gene expression. We report here the sequence of the IME1 gene and the consequences of IME1 expression from the GAL1 promoter. The deduced IME1 product is a 360-amino-acid protein with a tyrosine-rich C-terminal region. Expression of PGAL1-IME1 in vegetative a/alpha cells led to moderate accumulation of four early sporulation-specific transcripts (IME2, SPO11, SPO13, and HOP1); the transcripts accumulated 3- to 10-fold more after starvation. Two sporulation-specific transcripts normally expressed later (SPS1 and SPS2) did not accumulate until PGAL1-IME1 strains were starved, and the intact IME1 gene was not activated by PGAL1-IME1 expression. In a or alpha cells, which lack alpha 2 or a1, expression of PGAL1-IME1 led to the same pattern of IME2 and SPO13 expression as in a/alpha cells, as measured with ime2::lacZ and spo13::lacZ fusions. Thus, in wild-type strains, the increased expression of IME1 in starved a/alpha cells can account entirely for cell type control, but only partially for nutritional control, of early sporulation-specific gene expression. PGAL1-IME1 expression did not cause growing cells to sporulate but permitted efficient sporulation of amino acid-limited cells, which otherwise sporulated poorly. We suggest that IME1 acts primarily as a positive regulator of early sporulation-specific genes and that growth arrest is an independent prerequisite for execution of the sporulation program.

scholarly journals Testosterone Affects Neural Gene Expression Differently in Male and Female Juncos: A Role for Hormones in Mediating Sexual Dimorphism and Conflict

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e61784 ◽  
Author(s):  
Mark P. Peterson ◽  
Kimberly A. Rosvall ◽  
Jeong-Hyeon Choi ◽  
Charles Ziegenfus ◽  
Haixu Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Male And Female

scholarly journals Sex diversity in proximal tubule and endothelial gene expression in mice with ischemic acute kidney injury

2020 ◽  
Vol 134 (14) ◽  
pp. 1887-1909
Author(s):  
Jose L. Viñas ◽  
Christopher J. Porter ◽  
Adrianna Douvris ◽  
Matthew Spence ◽  
Alex Gutsol ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Hepatitis A Virus ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Ischemic Injury ◽  
Gene Profiling ◽  
Specific Gene ◽  
Male And Female ◽  
Female Mice

Abstract Female sex protects against development of acute kidney injury (AKI). While sex hormones may be involved in protection, the role of differential gene expression is unknown. We conducted gene profiling in male and female mice with or without kidney ischemia–reperfusion injury (IRI). Mice underwent bilateral renal pedicle clamping (30 min), and tissues were collected 24 h after reperfusion. RNA-sequencing (RNA-Seq) was performed on proximal tubules (PTs) and kidney endothelial cells. Female mice were resistant to ischemic injury compared with males, determined by plasma creatinine and neutrophil gelatinase-associated lipocalin (NGAL), histologic scores, neutrophil infiltration, and extent of apoptosis. Sham mice had sex-specific gene disparities in PT and endothelium, and male mice showed profound gene dysregulation with ischemia–reperfusion compared with females. After ischemia PTs from females exhibited smaller increases compared with males in injury-associated genes lipocalin-2 (Lcn2), hepatitis A virus cellular receptor 1 (Havcr1), and keratin 18 (Krt18), and no up-regulation of SRY-Box transcription factor 9 (Sox9) or keratin 20 (Krt20). Endothelial up-regulation of adhesion molecules and cytokines/chemokines occurred in males, but not females. Up-regulated genes in male ischemic PTs were linked to tumor necrosis factor (TNF) and Toll-like receptor (TLR) pathways, while female ischemic PTs showed up-regulated genes in pathways related to transport. The data highlight sex-specific gene expression differences in male and female PTs and endothelium before and after ischemic injury that may underlie disparities in susceptibility to AKI.

Sex-related Differences in Gene Expression in Salivary Glands of BALB/c Mice

2005 ◽  
Vol 84 (2) ◽  
pp. 160-165 ◽  
Author(s):  
N.S. Treister ◽  
S.M. Richards ◽  
M.J. Lombardi ◽  
P. Rowley ◽  
R.V. Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Salivary Glands ◽  
Structure And Function ◽  
Differentially Expressed ◽  
Male And Female ◽  
Tissue Specific ◽  
Total Rna ◽  
Males And Females ◽  
And Function

Sex-related differences exist in the structure and function of the major glands in a variety of species. Moreover, many of these variations appear to be unique to each tissue. We hypothesized that this sexual dimorphism is due, at least in part, to gland-specific differences in gene expression between males and females. Glands were collected from male and female BALB/c mice (n = 5/sex/experiment), and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs with CodeLink microarrays, and data were evaluated by GeneSifter. Our results demonstrate that significant (P < 0.05) sex-related differences exist in the expression of numerous genes in the major salivary glands, and many of these differences were tissue-specific. These findings support our hypothesis that sex-related differences in the salivary glands are due, at least in part, to tissue-specific variations in gene expression.

scholarly journals A Ubiquitin-Conjugating Enzyme Is Essential for Developmental Transitions in Dictyostelium

1997 ◽  
Vol 8 (10) ◽  
pp. 1989-2002 ◽  
Author(s):  
Alexandra Clark ◽  
Anson Nomura ◽  
Sudhasri Mohanty ◽  
Richard A. Firtel
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Specific Gene ◽  
Wild Type ◽  
Cell Type ◽  
Protein Ubiquitination ◽  
High Amino Acid ◽  
Cell Type Specific ◽  
Very High

We have identified a developmentally essential gene,UbcB, by insertional mutagenesis. The encoded protein (UBC1) shows very high amino acid sequence identity to ubiquitin-conjugating enzymes from other organisms, suggesting that UBC1 is involved in protein ubiquitination and possibly degradation during Dictyostelium development. Consistent with the homology of the UBC1 protein to UBCs, the developmental pattern of protein ubiquitination is altered in ubcB-null cells.ubcB-null cells are blocked in the ability to properly execute the developmental transition that occurs between the induction of postaggregative gene expression during mound formation and the induction of cell-type differentiation and subsequent morphogenesis.ubcB-null cells plated on agar form mounds with normal kinetics; however, they remain at this stage for ∼10 h before forming multiple tips and fingers that then arrest. Under other conditions, some of the fingers form migrating slugs, but no culmination is observed. In ubcB-null cells, postaggregative gene transcripts accumulate to very high levels and do not decrease significantly with time as they do in wild-type cells. Expression of cell-type-specific genes is very delayed, with the level of prespore-specific gene expression being significantly reduced compared with that in wild-type cells. lacZ reporter studies using developmentally regulated and cell-type-specific promoters suggest that ubcB-null cells show an unusually elevated level of staining of lacZ reporters expressed in anterior-like cells, a regulatory cell population found scattered throughout the aggregate, and reduced staining of a prespore reporter.ubcB-null cells in a chimeric organism containing predominantly wild-type cells are able to undergo terminal differentiation but show altered spatial localization. In contrast, in chimeras containing only a small fraction of wild-type cells, the mature fruiting body is very small and composed almost exclusively of wild-type cells, with the ubcB-null cells being present as a mass of cells located in extreme posterior of the developing organism. The amino acid sequence analysis of the UbcBopen reading frame (ORF) and the analysis of the developmental phenotypes suggest that tip formation and subsequent development requires specific protein ubiquitination, and possibly degradation.

scholarly journals Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Zeyu Cai ◽  
Congcong Yang ◽  
Jun Liao ◽  
Haifeng Song ◽  
Sheng Zhang
Keyword(s):  
Gene Expression ◽  
Energy Consumption ◽  
Sexual Dimorphism ◽  
Molecular Mechanisms ◽  
Temporal Dynamics ◽  
Biomass Accumulation ◽  
Reproductive Costs ◽  
Male And Female ◽  
Unisexual Flowers ◽  
Male Flowers

AbstractDioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism in S. paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression in S. paraplesia flowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.

scholarly journals Sex-specific expression and DNA methylation in a species with extreme sexual dimorphism and paternal genome elimination

2020 ◽  
Author(s):  
Stevie A. Bain ◽  
Hollie Marshall ◽  
Laura Ross
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Alternative Splicing ◽  
Sexual Dimorphism ◽  
Planococcus Citri ◽  
Specific Gene ◽  
Paternal Genome ◽  
Specific Expression ◽  
Cis Acting ◽  
Genome Wide

AbstractSexual dimorphism is exhibited in many species across the tree of life with many phenotypic differences mediated by differential expression and alternative splicing of genes present in both sexes. However, the mechanisms that regulate these sex-specific expression and splicing patterns remain poorly understood. The mealybug, Planococcus citri, displays extreme sexual dimorphism and exhibits an unusual instance of sex-specific genomic imprinting, Paternal Genome Elimination (PGE), in which the paternal chromosomes in males are highly condensed and eliminated from the sperm. P. citri also has no sex chromosomes and as such both sexual dimorphism and PGE are predicted to be under epigenetic control. We recently showed that P. citri females display a highly unusual DNA methylation profile for an insect species, with the presence of promoter methylation associated with lower levels of gene expression. In this study we therefore decided to explore genome-wide differences in DNA methylation between male and female P. citri using whole genome bisulfite sequencing. We have identified extreme differences in genome-wide levels and patterns between the sexes. Males display overall higher levels of DNA methylation which manifests as more uniform low-levels across the genome. Whereas females display more targeted high levels of methylation. We suggest these unique sex-specific differences are due to chromosomal differences caused by PGE and may be linked to possible ploidy compensation. Using RNA-Seq we identified extensive sex-specific gene expression and alternative splicing. We found cis-acting DNA methylation is not directly associated with differentially expressed or differentially spliced genes, indicating a broader role for chromosome-wide trans-acting DNA methylation in this species.

scholarly journals A neuron-optimized CRISPR/dCas9 activation system for robust and specific gene regulation

2018 ◽  
Author(s):  
Katherine E. Savell ◽  
Svitlana V. Bach ◽  
Morgan E. Zipperly ◽  
Jasmin S. Revanna ◽  
Nicholas A. Goska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Transcriptional Activation ◽  
Target Genes ◽  
Adult Brain ◽  
Model Systems ◽  
Neuronal Cultures ◽  
Specific Gene ◽  
Highly Efficient ◽  
Study Gene Expression

Recent developments in CRISPR-based gene editing have provided new avenues to interrogate gene function. However, application of these tools in the central nervous system has been delayed due to difficulties in transgene expression in post-mitotic neurons. Here, we present a highly efficient, neuron-optimized dual lentiviral CRISPR-based transcriptional activation (CRISPRa) system to drive gene expression in primary neuronal cultures and the adult brain of rodent model systems. We demonstrate robust, modular, and tunable induction of endogenous target genes as well as multiplexed gene regulation necessary for investigation of complex transcriptional programs. CRISPRa targeting unique promoters in the complex multi-transcript gene Brain-derived neurotrophic factor (Bdnf) revealed both transcript- and genome-level selectivity of this approach, in addition to highlighting downstream transcriptional and physiological consequences of Bdnf regulation. Finally, we illustrate that CRISPRa is highly efficient in vivo, resulting in increased protein levels of a target gene in diverse brain structures. Taken together, these results demonstrate that CRISPRa is an efficient and selective method to study gene expression programs in brain health and disease.

scholarly journals Gene duplication, tissue-specific gene expression and sexual conflict in stalk-eyed flies (Diopsidae)

2012 ◽  
Vol 367 (1600) ◽  
pp. 2357-2375 ◽  
Author(s):  
Richard H. Baker ◽  
Apurva Narechania ◽  
Philip M. Johns ◽  
Gerald S. Wilkinson
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Gene Duplication ◽  
Sexual Conflict ◽  
Morphological Evolution ◽  
Expression Patterns ◽  
Genetic Material ◽  
Genomic Research ◽  
Specific Gene ◽  
Duplicated Genes

Gene duplication provides an essential source of novel genetic material to facilitate rapid morphological evolution. Traits involved in reproduction and sexual dimorphism represent some of the fastest evolving traits in nature, and gene duplication is intricately involved in the origin and evolution of these traits. Here, we review genomic research on stalk-eyed flies (Diopsidae) that has been used to examine the extent of gene duplication and its role in the genetic architecture of sexual dimorphism. Stalk-eyed flies are remarkable because of the elongation of the head into long stalks, with the eyes and antenna laterally displaced at the ends of these stalks. Many species are strongly sexually dimorphic for eyespan, and these flies have become a model system for studying sexual selection. Using both expressed sequence tag and next-generation sequencing, we have established an extensive database of gene expression in the developing eye-antennal imaginal disc, the adult head and testes. Duplicated genes exhibit narrower expression patterns than non-duplicated genes, and the testes, in particular, provide an abundant source of gene duplication. Within somatic tissue, duplicated genes are more likely to be differentially expressed between the sexes, suggesting gene duplication may provide a mechanism for resolving sexual conflict.

scholarly journals Microvascular Sex- and Age- Dependent Phosphodiesterase Expression

2021 ◽  
Vol 2 ◽  
Author(s):  
Jianjie Wang ◽  
Murtaza M. Kazmi ◽  
Virginia H. Huxley
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Sexual Dimorphism ◽  
Cyclic Nucleotide ◽  
Female Rats ◽  
Adult Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Age Dependent ◽  
Camp And Cgmp

Objective: The cyclic nucleotide second messengers, cAMP and cGMP, are pivotal regulators of vascular functions; their cellular levels are tightly controlled by the cyclic nucleotide hydrolases, phosphodiesterases (PDE). Biologic sex and age are recognized as independent factors impacting the mechanisms mediating both vascular health and dysfunction. This study focused on microvessels isolated from male and female rats before (juvenile) and after (adult) sexual maturity under resting conditions. We tested the hypothesis that sexual dimorphism in microvascular PDE expression would be absent in juvenile rats, but would manifest in adult rats.Methods: Abdominal skeletal muscle arterioles and venules were isolated from age-matched juvenile and adult male and female rats under resting conditions. Transcripts of five PDE families (1–5) associated with coronary and vascular function with a total of ten genes were measured using TaqMan real-time RT-PCR and protein expression of microvessel PDE4 was assessed using immunoblotting and immunofluorescence.Results: Overall expression levels of PDE5A were highest while PDE3 levels were lowest among the five PDE families (p &lt; 0.05) regardless of age or sex. Contrary to our hypothesis, in juveniles, sexual dimorphism in PDE expression was observed in three genes: arterioles (PDE1A, female &gt; male) and venules (PDE1B and 3A, male &gt; female). In adults, gene expression levels in males were higher than females for five genes in arterioles (PDE1C, 3A, 3B, 4B, 5A) and three genes (PDE3A, 3B, and 5A) in venules. Furthermore, age-related differences were observed in PDE1-5 (in males, adult &gt; juvenile for most genes in arterioles; in females, adult &gt; juvenile for arteriolar PDE3A; juvenile gene expression &gt; adult for two genes in arterioles and three genes in venules). Immunoblotting and immunofluorescence analysis revealed protein expression of microvessel PDE4.Conclusion: This study revealed sexual dimorphism in both juvenile and adult rats, which is inconsistent with our hypothesis. The sex- and age-dependent differences in PDE expression implicate different modulations of cAMP and cGMP pathways for microvessels in health. The implication of these sex- and age-dependent differences, as well as the duration and microdomain of PDE1-5 activities in skeletal muscle microvessels, in both health and disease, require further investigation.

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