Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II–Induced Aortopathies

Objective: Turner syndrome women (monosomy X) have high risk of aortopathies consistent with a role for sex chromosomes in disease development. We demonstrated that sex chromosomes influence regional development of Ang II (angiotensin II)–induced aortopathies in mice. In this study, we determined if the number of X chromosomes regulates regional development of Ang II–induced aortopathies. Approach and Results: We used females with varying numbers of X chromosomes (XX female mice [XXF] or XO female mice [XOF]) on an C57BL/6J (ascending aortopathies) or low-density lipoprotein receptor deficient ( Ldlr −/− ) background (descending and abdominal aortopathies) compared with XY males (XYM). To induce aortopathies, mice were infused with Ang II. XOF (C57BL/6J) exhibited larger percent increases in ascending aortic lumen diameters than Ang II–infused XXF or XYM. Ang II–infused XOF ( Ldlr −/− ) exhibited similar incidences of thoracic (XOF, 50%; XYM, 71%) and abdominal aortopathies (XOF, 83%; XYM, 71%) as XYM, which were greater than XXF (XXF, 0%). Abdominal aortic lumen diameters and maximal external diameters were similar between XOF and XYM but greater than XXF, and these effects persisted with extended Ang II infusions. Larger aortic lumen diameters, abdominal aortopathy incidence (XXF, 20%; XOF, 75%), and maximal aneurysm diameters (XXF, 1.02±0.17; XOF, 1.96±0.32 mm; P =0.027) persisted in ovariectomized Ang II–infused XOF mice. Data from RNA-seq demonstrated that X chromosome genes that escape X-inactivation (histone lysine demethylases Kdm5c and Kdm6a ) exhibited lower mRNA abundance in aortas of XOF than XXF ( P =0.033 and 0.024, respectively). Conversely, DNA methylation was higher in aortas of XOF than XXF ( P =0.038). Conclusions: The absence of a second X chromosome promotes diffuse Ang II–induced aortopathies in females.

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Bisection of the X chromosome disrupts the initiation of chromosome silencing during meiosis in Caenorhabditis elegans

Nature Communications ◽

10.1038/s41467-021-24815-0 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yisrael Rappaport ◽

Hanna Achache ◽

Roni Falk ◽

Omer Murik ◽

Oren Ram ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Rna Polymerase Ii ◽

X Chromosome ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Transcription Analysis ◽

X Chromosomes ◽

Unique Character ◽

Active Transcription ◽

Heterogametic Sex

AbstractDuring meiosis, gene expression is silenced in aberrantly unsynapsed chromatin and in heterogametic sex chromosomes. Initiation of sex chromosome silencing is disrupted in meiocytes with sex chromosome-autosome translocations. To determine whether this is due to aberrant synapsis or loss of continuity of sex chromosomes, we engineered Caenorhabditis elegans nematodes with non-translocated, bisected X chromosomes. In early meiocytes of mutant males and hermaphrodites, X segments are enriched with euchromatin assembly markers and active RNA polymerase II staining, indicating active transcription. Analysis of RNA-seq data showed that genes from the X chromosome are upregulated in gonads of mutant worms. Contrary to previous models, which predicted that any unsynapsed chromatin is silenced during meiosis, our data indicate that unsynapsed X segments are transcribed. Therefore, our results suggest that sex chromosome chromatin has a unique character that facilitates its meiotic expression when its continuity is lost, regardless of whether or not it is synapsed.

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Abstract 7: Angiotensin II Type 2 Receptor Deficiency Increases Renal ACE/ACE2 Ratio-Ang II-AT1R Expression In Male but not in Female Mice

Hypertension ◽

10.1161/hyp.60.suppl_1.a7 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Quaisar Ali ◽

Yonnie Wu ◽

Tadashi Inagami ◽

Tahir Hussain

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Angiotensin Ii ◽

Renin Activity ◽

Ang Ii ◽

Male And Female ◽

Female Mice ◽

Gender Specific

Angiotensin II acting via Angiotensin II type 2 receptors (AT2Rs) is believed to be protective against blood pressure increase and affects renal function under pathophysiological condition. Recently we have observed that stimulation of AT2Rs in male obese Zucker rats has shifted the two opposing arms of renin angiotensin system (RAS) i.e. ACE-Ang II-AT1 vs ACE2/Ang-(1-7)-Mas. Evidence suggests that estrogen regulates RAS, including AT2R in female mice. We hypothesized that AT2R has a gender specific regulation of RAS. In the present study, we investigated the role of AT2Rs in regulating RAS components in male and female mice. Kidney cortex from AT2R knockout (AT2RKO) male and female mice and wild type (WT) with similar background (C57BL/6) of 20 weeks of age were used in the study. The cortical ACE expression (ng ACE/μg tissue) was significantly increased in AT2RKO mice (3±0.02) compared to WT males (1.9±0.02). LC/MS analysis of cortical tissue revealed that Ang II was also significantly increased in AT2RKO mice (WT: 31±3, AT2RKO: 47±3 fmoles/mg tissue). Deletion of AT2R significantly increased AT1R (204%, 204 of 100) expression and had no effect on renin activity compared to WT males. The cortical expression of ACE2 activity (WT: 113±8, AT2RKO: 40±11, RFU/min), Ang-(1-7) levels (WT: 7.3±1.4, AT2RKO: 3±0.8 fmoles/mg tissue) and Mas receptor (AT2RKO: 54±15, % of WT) was significantly decreased in AT2RKO males compared to WT. The cortical expression of the AT2R and MasR was 2-fold greater in WT females compared to WT male. The renin activity (WT: 32±2, AT2RKO: 21±0.3, RFU/min) and MasR expression (WT: 187.5±55, AT2KO: 47±9) was significantly decreased in AT2RKO females compared to the female WT. Interestingly, Ang-(1-7) level (WT: 5.7±0.7, AT2RKO 2.6±0.7 fmoles/mg tissue) was decreased but no changes in ACE or ACE2 activity was observed in AT2KO females compared to their WT, suggesting a role of non-ACE2 pathway. This study suggests that AT2R regulates ACE/ACE2 ratio-Ang II-AT1R expression negatively only in males, whereas in females, it regulates Ang-(1-7) potentially via non-ACE2 pathway. Such changes indicate a gender specific mechanisms potentially associated with AT2R-mediated regulation of renal function and blood pressure control.

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Abstract 598: Deletion of Microsomal PGE Synthase-1 Decreases Oxidative Stress and Protects Against Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Mice

Circulation ◽

10.1161/circ.116.suppl_16.ii_108-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Miao Wang ◽

Jane Stubbe ◽

Eric Lee ◽

Wenliang Song ◽

Emanuela Ricciotti ◽

...

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Aortic Aneurysms ◽

Ang Ii ◽

Abdominal Aortic ◽

Density Lipoprotein Receptor ◽

The Impact

Microsomal (m) prostaglandin (PG) E 2 synthase(S)-1, an enzyme that catalyzes the isomerization of the cyclooxygenase (COX) product, PGH 2 , into PGE 2 , is a major source of PGE 2 in vivo . mPGES-1 deletion in mice was found to modulate experimentally evoked pain and inflammation and atherogenesis is retarded in mPGES-1 knockout (KO) mice. The impact of mPGES-1 deletion on formation of angiotensin II (Ang II)-induced abdominal aortic aneurysms (AAA) was studied in mice lacking the low density lipoprotein receptor (LDLR −/− ). AngII infusion increased aortic macrophage recruitment and nitrotyrosine staining while upregulating both mPGES-1 and COX-2 and urinary excretion of the major metabolite of PGE 2 (PGE-M). Deletion of mPGES-1 decreased both the incidence and severity of AAA and depressed excretion of both PGE-M and 8, 12-iso-iPF 2a -VI, which reflects lipid peroxidation in vivo . While Ang II infusion augmented prostaglandin biosynthesis, deletion of mPGES-1 resulted in rediversion to PGD 2 , reflected by its major urinary metabolite. However, deletion of the PGD 2 receptor, DP1, did not affect AAA in Ang II infused LDLR −/− mice. These observations indicate that deletion of mPGES-1 protects against AAA formation by AngII in hyperlipidemic mice, perhaps by decreasing oxidative stress. Inhibition of mPGES-1 may represent an effective treatment to limit aneurysm occurrence and expansion.

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A Syntenic Region Conserved from Fish to Mammalian X Chromosome

International Journal of Evolutionary Biology ◽

10.1155/2014/873935 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10

Author(s):

Guijun Guan ◽

Meisheng Yi ◽

Tohru Kobayashi ◽

Yunhan Hong ◽

Yoshitaka Nagahama

Keyword(s):

X Chromosome ◽

Sex Chromosomes ◽

Random Amplified Polymorphic Dna ◽

Comparative Genomic ◽

X Chromosomes ◽

Ancestral Origin ◽

Dna Contents ◽

Determining Factors ◽

Unpaired Region ◽

Syntenic Segment

Sex chromosomes bearing the sex-determining gene initiate development along the male or female pathway, no matter which sex is determined by XY male or ZW female heterogamety. Sex chromosomes originate from ancient autosomes but evolved rapidly after the acquisition of sex-determining factors which are highly divergent between species. In the heterogametic male system (XY system), the X chromosome is relatively evolutionary silent and maintains most of its ancestral genes, in contrast to its Y counterpart that has evolved rapidly and degenerated. Sex in a teleost fish, the Nile tilapia (Oreochromis niloticus), is determined genetically via an XY system, in which an unpaired region is present in the largest chromosome pair. We defined the differences in DNA contents present in this chromosome with a two-color comparative genomic hybridization (CGH) and the random amplified polymorphic DNA (RAPD) approach in XY males. We further identified a syntenic segment within this region that is well conserved in several teleosts. Through comparative genome analysis, this syntenic segment was also shown to be present in mammalian X chromosomes, suggesting a common ancestral origin of vertebrate sex chromosomes.

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Studies on Metatherian Sex Chromosomes. IX. Sex Chromosomes of the Greater Glider (Marsupialia : Petauridae)

Australian Journal of Biological Sciences ◽

10.1071/bi9790375 ◽

1979 ◽

Vol 32 (3) ◽

pp. 375 ◽

Cited By ~ 3

Author(s):

JD Murray ◽

GM McKay ◽

GB Sharman

Keyword(s):

X Chromosome ◽

Sex Chromosomes ◽

National Park ◽

Secondary Constriction ◽

X Chromosomes ◽

Cultured Fibroblasts ◽

Multiple Sex Chromosomes ◽

Eastern Australia ◽

Xy Bivalent ◽

Secondary Constrictions

The greater glider, currently but incorrectly known as Schoinobates vo/ans, is widely distributed in forested regions in eastern Australia. All animals studied from six different localities had 20 autosomes but there were four chromosomally distinct populations. At Royal National Park, N.S.W., all female greater gliders studied had 22 chromosomes including two large submetacentric X chromosomes with subterminal secondary constrictions in their longer arms. This form of X chromosome occurred also at Bondo State Forest, Myall Lakes and Coff's Harbour, N.S.W., and at Eidsvold, Qld. At Coomooboolaroo, Qld, the X chromosome was also a large submetacentric but a secondary constriction occurred in the shorter arm. Two chromosomally distinct types apparently occur in Royal National Park, one with XY m,ales as in all other populations, and one with XY1Y2 males. Y or Yb but not Y 2, chromosomes were eliminated from the bone marrow in all populations but were present in spermatogonia, primary sperrnatocytes and cultured fibroblasts. Animals from Bondo State Forest had three or more acrocentric or metacentric supernumerary chromosomes. [Other keywords: C-banding, eytotaxonomy, multiple sex chromosomes, XY bivalent.]

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B-Type Natriuretic Peptide Inhibited Angiotensin II-Stimulated Cholesterol Biosynthesis, Cholesterol Transfer, and Steroidogenesis in Primary Human Adrenocortical Cells

Endocrinology ◽

10.1210/en.2006-1599 ◽

2007 ◽

Vol 148 (8) ◽

pp. 3722-3729 ◽

Cited By ~ 22

Author(s):

Faquan Liang ◽

Ann M. Kapoun ◽

Andrew Lam ◽

Debby L. Damm ◽

Diana Quan ◽

...

Keyword(s):

Angiotensin Ii ◽

Mitochondrial Membrane ◽

Coenzyme A ◽

Cholesterol Biosynthesis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Ang Ii ◽

Inner Mitochondrial Membrane ◽

Adrenocortical Cells

In this study, we demonstrate that B-type natriuretic peptide (BNP) opposed angiotensin II (Ang II)-stimulated de novo cholesterol biosynthesis, cellular cholesterol uptake, cholesterol transfer to the inner mitochondrial membrane, and steroidogenesis, which are required for biosynthesis of steroid hormones such as aldosterone and cortisol in primary human adrenocortical cells. BNP dose-dependently stimulated intracellular cGMP production with an EC50 of 11 nm, implying that human adrenocortical cells express the guanylyl cyclase A receptor. cDNA microarray and real-time RT-PCR analyses revealed that BNP inhibited Ang II-stimulated genes related to cholesterol biosynthesis (acetoacetyl coenzyme A thiolase, HMG coenzyme A synthase 1, HMG coenzyme A reductase, isopentenyl-diphosphate Δ-isomerase, lanosterol synthase, sterol-4C-methyl oxidase, and emopamil binding protein/sterol isomerase), cholesterol uptake from circulating lipoproteins (scavenger receptor class B type I and low-density lipoprotein receptor), cholesterol transfer to the inner mitochondrial membrane (steroidogenic acute regulatory protein), and steroidogenesis (ferredoxin 1,3β-hydroxysteroid dehydrogenase, glutathione transferase A3, CYP19A1, CYP11B1, and CYP11B2). Consistent with the microarray and real-time PCR results, BNP also blocked Ang II-induced binding of 125I-labeled low-density lipoprotein and 125I-labeled high-density lipoprotein to human adrenocortical cells. Furthermore, BNP markedly inhibited Ang II-stimulated release of estradiol, aldosterone, and cortisol from cultured primary human adrenocortical cells. These findings demonstrate that BNP opposes Ang II-induced steroidogenesis via multiple steps from cholesterol supply and transfer to the final formation of steroid hormones. This study provides new insights into the cellular mechanisms by which BNP modulates Ang II-induced steroidogenesis in the adrenal gland.

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Dosage compensation in sciarids is achieved by hypertranscription of the single X chromosome in males.

Genetics ◽

10.1093/genetics/138.3.787 ◽

1994 ◽

Vol 138 (3) ◽

pp. 787-790

Author(s):

P R da Cunha ◽

B Granadino ◽

A L Perondini ◽

L Sánchez

Keyword(s):

X Chromosome ◽

Dosage Compensation ◽

Sex Chromosomes ◽

Sex Chromosome ◽

X Chromosomes ◽

Different Doses

Abstract Dosage compensation refers to the process whereby females and males with different doses of sex chromosomes have similar amounts of products from sex chromosome-linked genes. We analyzed the process of dosage compensation in Sciara ocellaris, Diptera of the suborder Nematocera. By autoradiography and measurements of X-linked rRNA in females (XX) and males (XO), we found that the rate of transcription of the single X chromosome in males is similar to that of the two X chromosomes in females. This, together with the bloated appearance of the X chromosome in males, support the idea that in sciarids dosage compensation is accomplished by hypertranscription of the X chromosome in males.

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Studies on Metatherian Sex Chromosomes III. The Use of Tritiated Uridine-induced Chromosome Aberrations to Distinguish Active and Inactive X Chromosomes

Australian Journal of Biological Sciences ◽

10.1071/bi9770103 ◽

1977 ◽

Vol 30 (2) ◽

pp. 103 ◽

Cited By ~ 6

Author(s):

Jennifer A Donald ◽

DW Cooper

Keyword(s):

X Chromosome ◽

Sex Chromosomes ◽

Chromosome Aberrations ◽

X Inactivation ◽

Facultative Heterochromatin ◽

Hybrid Female ◽

X Chromosomes ◽

Toxicity Effect ◽

Red Kangaroo ◽

Chromosome Regions

The paternal X inactivation system of kangaroos has been investigated in this study by using tritiated uridine-induced chromosome aberrations to distinguish the active from the inactive X. Previous work in eutherian mammals has demonstrated that constitutive heterochromatic chromosome regions are less susceptible to breakage by tritiated uri dine than euchromatic regions. The results of a comparison between the paternal X chromosome of a wallaroo x red kangaroo hybrid female and the two X chromosomes of a red kangaroo female suggested that the facultative heterochromatin of the X is also less susceptible to breakage by this treatment. However there were significantly more breaks of the paternal X in fibroblasts than in lymphocytes of the hybrid female, which agrees with biochemical findings suggesting activation of the paternal X in fibroblasts. Our results strengthen the suggestion of other workers that the reduced number of aberrations in heterochromatin occurs because such breaks occur principally when the DNA and labelled RNA are in apposition during transcription. Some evidence was found of an apparent toxicity effect of the tritiated uridine solution on the cells.

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Identification of sex chromosomes using genomic and cytogenetic methods in a range-expanding spider, Argiope bruennichi (Araneae: Araneidae)

10.1101/2021.10.06.463373 ◽

2021 ◽

Author(s):

Monica M Sheffer ◽

Mathilde M Cordellier ◽

Martin Forman ◽

Malte Grewoldt ◽

Katharina Hoffmann ◽

...

Keyword(s):

X Chromosome ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Chromosome Complement ◽

Gc Content ◽

Sexually Dimorphic ◽

Behavioral Experiments ◽

X Chromosomes ◽

Male Karyotype ◽

And Behavior

Differences between sexes in growth, ecology and behavior strongly shape species biology. In some animal groups, such as spiders, it is difficult or impossible to identify the sex of juveniles. This information would be useful for field surveys, behavioral experiments, and ecological studies on e.g. sex ratios and dispersal. In species with sex chromosomes, sex can be determined based on the specific sex chromosome complement. Additionally, information on the sequence of sex chromosomes provides the basis for studying sex chromosome evolution. We combined cytogenetic and genomic data to identify the sex chromosomes in the sexually dimorphic spider Argiope bruennichi, and designed RT-qPCR sex markers. We found that genome size and GC content of this spider falls into the range reported for the majority of araneids. The male karyotype is formed by 24 acrocentric chromosomes with an X1X20 sex chromosome system, with little similarity between X chromosomes, suggesting origin of these chromosomes by X chromosome fission or early duplication of an X chromosome and subsequent independent differentiation of the copies. Our data suggest similarly sized X chromosomes in A. bruennichi. They are smaller chromosomes of the complement. Our findings open the door to new directions in spider evolutionary and ecological research.

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Abstract 513: Evaluation of Proinflammatory Effects of Low Dose Angiotensin II Infusion in Intact Female Mice and Adiponectin Deficient Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.513 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Esther Yu ◽

Xia Wang ◽

Jaya Pamidimukkala

Keyword(s):

Angiotensin Ii ◽

Mrna Expression ◽

Adhesion Molecules ◽

Endothelial Activation ◽

Tissue Expression ◽

Renal Tissue ◽

Protective Effects ◽

Ang Ii ◽

Female Mice ◽

Deficient Mice

Circulating vasoactive peptide Angiotensin II (ANGII) has a well-known role in the development of hypertension and other cardiovascular diseases. In addition it has significant proinflammatory actions in the vascular wall inducing the production of reactive oxygen species, inflammatory cytokines and adhesion molecules. It has been previously shown that estrogen in female mice protects against ANGII mediated hypertension and against proinflammatory effects. It is not clear if the protective effects of estrogen extend to adiponectin deficient mice. Adiponectin is one of the few peptides secreted by fat to have anti-inflammatory properties. The present study evaluates the effect of chronic ANGII infusion on expression of cytokines in female C57BL/6J and adiponectin deficient mice (adipo-/-). Female mice (24- 28wks), were implanted with osmotic pump containing either ANG II (800 ng/Kg /min) or saline. Blood samples and tissue were collected at the end of 14 days. Plasma levels of TNFalpha and IL6 were measured using enzyme linked immunoabsorbent assay. Renal tissue expression of the cytokines were quantified using real-time PCR (Eppendorf Realplex 4 mastercycler) and SYBR Green ROX mastermix. Plasma TNFα levels were similar in saline infused C57Bl/6J(11±1 pg/ml) and adiponectin deficient mice(10± 1 pg/ml). ANGII did not significantly increase TNFα in the control(14±3 pg/ml) or adipo-/- mice(13+1 pg/ml). Plasma IL6 levels were also not significantly different in the two groups. A microarray for mRNA expression of markers of endothelial activation and adhesion molecules was also performed in the renal tissue. Preliminary data show that TNFalpha mRNA expression levels were not increased by ANG II infusion and IL6 expression was undetectable. ANGII also did not alter E-Selectin,VCAM1, Collagen1a1 and eNOS expression. In conclusion, ANGII infusion did not result in a proinflammatory milieu in both female C57BL/6J and Adipo -/- mice.

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