Gonadal hormones and sex chromosome complement differentially contribute to ethanol intake, preference, and relapse-like behavior in Four Core Genotypes mice

AbstractAlcohol use and high-risk alcohol drinking behaviors among women are rapidly rising. In rodent models, females typically consume more ethanol (EtOH) than males. Here, we used the Four Core Genotypes (FCG) mouse model to investigate the influence of gonadal hormones and sex chromosome complement to EtOH drinking behaviors. FCG mice were given access to escalating concentrations of EtOH in a two-bottle, 24-h continuous access drinking paradigm to assess consumption and preference. Relapse-like behavior was measured by assessing escalated intake following repeated cycles of deprivation and re-exposure. Twenty-four hour EtOH consumption was greater in mice with ovaries (Sry−), relative to those with testes, and in mice with the XX chromosome complement, relative to those with XY sex chromosomes. EtOH preference was higher in XX vs. XY mice but not influenced by gonad type. Escalated intake following repeated cycles of deprivation and re-exposure emerged only in XX mice (vs. XY). These results demonstrate that aspects of EtOH drinking behavior may be independently regulated by sex hormones and chromosomes and inform our understanding of the neurobiological mechanisms which contribute to EtOH dependence in male and female mice. Future investigation of the contribution of sex chromosomes to EtOH drinking behaviors is warranted.

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X and Y Chromosome Complement Influence Adiposity and Metabolism in Mice

Endocrinology ◽

10.1210/en.2012-2098 ◽

2013 ◽

Vol 154 (3) ◽

pp. 1092-1104 ◽

Cited By ~ 50

Author(s):

Xuqi Chen ◽

Rebecca McClusky ◽

Yuichiro Itoh ◽

Karen Reue ◽

Arthur P. Arnold

Keyword(s):

Body Weight ◽

Y Chromosome ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Chromosome Complement ◽

Gonadal Hormones ◽

Xy Model ◽

Second Sex ◽

Metabolic Variables ◽

Novel Model

Abstract Three different models of MF1 strain mice were studied to measure the effects of gonadal secretions and sex chromosome type and number on body weight and composition, and on related metabolic variables such as glucose homeostasis, feeding, and activity. The 3 genetic models varied sex chromosome complement in different ways, as follows: 1) “four core genotypes” mice, comprising XX and XY gonadal males, and XX and XY gonadal females; 2) the XY* model comprising groups similar to XO, XX, XY, and XXY; and 3) a novel model comprising 6 groups having XO, XX, and XY chromosomes with either testes or ovaries. In gonadally intact mice, gonadal males were heavier than gonadal females, but sex chromosome complement also influenced weight. The male/female difference was abolished by adult gonadectomy, after which mice with 2 sex chromosomes (XX or XY) had greater body weight and percentage of body fat than mice with 1 X chromosome. A second sex chromosome of either type, X or Y, had similar effects, indicating that the 2 sex chromosomes each possess factors that influence body weight and composition in the MF1 genetic background. Sex chromosome complement also influenced metabolic variables such as food intake and glucose tolerance. The results reveal a role for the Y chromosome in metabolism independent of testes and gonadal hormones and point to a small number of X–Y gene pairs with similar coding sequences as candidates for causing these effects.

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Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes

Genetics Research ◽

10.1017/s0016672301005109 ◽

2001 ◽

Vol 78 (1) ◽

pp. 23-30 ◽

Cited By ~ 65

Author(s):

MARIKO KONDO ◽

ERIKO NAGAO ◽

HIROSHI MITANI ◽

AKIHIRO SHIMA

Keyword(s):

Genetic Map ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Oryzias Latipes ◽

Male Recombination ◽

Male And Female ◽

Y Chromosomes ◽

Genetic Length ◽

Expressed Sequence ◽

Group 1

In the medaka, Oryzias latipes, sex is determined chromosomally. The sex chromosomes differ from those of mammals in that the X and Y chromosomes are highly homologous. Using backcross panels for linkage analysis, we mapped 21 sequence tagged site (STS) markers on the sex chromosomes (linkage group 1). The genetic map of the sex chromosome was established using male and female meioses. The genetic length of the sex chromosome was shorter in male than in female meioses. The region where male recombination is suppressed is the region close to the sex-determining gene y, while female recombination was suppressed in both the telomeric regions. The restriction in recombination does not occur uniformly on the sex chromosome, as the genetic map distances of the markers are not proportional in male and female recombination. Thus, this observation seems to support the hypothesis that the heterogeneous sex chromosomes were derived from suppression of recombination between autosomal chromosomes. In two of the markers, Yc-2 and Casp6, which were expressed sequence-tagged (EST) sites, polymorphisms of both X and Y chromosomes were detected. The alleles of the X and Y chromosomes were also detected in O. curvinotus, a species related to the medaka. These markers could be used for genotyping the sex chromosomes in the medaka and other species, and could be used in other studies on sex chromosomes.

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Sex Differences in Ischemic Stroke Sensitivity Are Influenced by Gonadal Hormones, Not by Sex Chromosome Complement

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.186 ◽

2014 ◽

Vol 35 (2) ◽

pp. 221-229 ◽

Cited By ~ 66

Author(s):

Bharti Manwani ◽

Kathryn Bentivegna ◽

Sharon E Benashski ◽

Venugopal Reddy Venna ◽

Yan Xu ◽

...

Keyword(s):

Sex Differences ◽

Ischemic Stroke ◽

Sex Hormones ◽

Sex Chromosome ◽

Chromosome Complement ◽

Serum Testosterone ◽

Gonadal Hormones ◽

Epidemiologic Studies ◽

Artery Occlusion ◽

Male Mice

Epidemiologic studies have shown sex differences in ischemic stroke. The four core genotype (FCG) mouse model, in which the testes determining gene, Sry, has been moved from Y chromosome to an autosome, was used to dissociate the effects of sex hormones from sex chromosome in ischemic stroke outcome. Middle cerebral artery occlusion (MCAO) in gonad intact FCG mice revealed that gonadal males (XXM and XYM) had significantly higher infarct volumes as compared with gonadal females (XXF and XYF). Serum testosterone levels were equivalent in adult XXM and XYM, as was serum estrogen in XXF and XYF mice. To remove the effects of gonadal hormones, gonadectomized FCG mice were subjected to MCAO. Gonadectomy significantly increased infarct volumes in females, while no change was seen in gonadectomized males, indicating that estrogen loss increases ischemic sensitivity. Estradiol supplementation in gonadectomized FCG mice rescued this phenotype. Interestingly, FCG male mice were less sensitive to effects of hormones. This may be due to enhanced expression of the transgene Sry in brains of FCG male mice. Sex differences in ischemic stroke sensitivity appear to be shaped by organizational and activational effects of sex hormones, rather than sex chromosomal complement.

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Differential regulation of mouse hippocampal gene expression sex differences by chromosomal content and gonadal sex

10.1101/2021.09.01.458115 ◽

2021 ◽

Author(s):

Sarah R Ocanas ◽

Victor A Ansere ◽

Kyla B Tooley ◽

Niran Hadad ◽

Ana J Chucair-Elliott ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Sex Differences ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Chromosome Complement ◽

Experimental Models ◽

Ctcf Binding ◽

Autosomal Gene ◽

Sex Effects

Sex differences in the brain as they relate to health and disease are often overlooked in experimental models. Many neurological disorders, like Alzheimer's disease (AD), multiple sclerosis (MS), and autism, differ in prevalence between males and females. Sex differences originate either from differential gene expression on sex chromosomes or from hormonal differences, either directly or indirectly. To disentangle the relative contributions of genetic sex (XX v. XY) and gonadal sex (ovaries v. testes) to the regulation of hippocampal sex effects, we use the "sex-reversal" Four Core Genotype (FCG) mouse model which uncouples sex chromosome complement from gonadal sex. Transcriptomic and epigenomic analyses of hippocampal RNA and DNA from ~12 month old FCG mice, reveals differential regulatory effects of sex chromosome content and gonadal sex on X- versus autosome-encoded gene expression and DNA modification patterns. Gene expression and DNA methylation patterns on the X chromosome were driven primarily by sex chromosome content, not gonadal sex. The majority of DNA methylation changes involved hypermethylation in the XX genotypes (as compared to XY) in the CpG context, with the largest differences in CpG islands, promoters, and CTCF binding sites. Autosomal gene expression and DNA modifications demonstrated regulation by sex chromosome complement and gonadal sex. These data demonstrate the importance of sex chromosomes themselves, independent of hormonal status, in regulating hippocampal sex effects. Future studies will need to further interrogate specific CNS cell types, identify the mechanisms by which sex chromosome regulate autosomes, and differentiate organizational from activational hormonal effects.

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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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Interaction of sex chromosome complement, gonadal hormones and neuronal steroid synthesis on the sexual differentiation of mammalian neurons

Journal of Neurogenetics ◽

10.1080/01677063.2017.1390572 ◽

2017 ◽

Vol 31 (4) ◽

pp. 300-306 ◽

Cited By ~ 12

Author(s):

Maria Julia Cambiasso ◽

Carla Daniela Cisternas ◽

Isabel Ruiz-Palmero ◽

Maria Julia Scerbo ◽

Maria Angeles Arevalo ◽

...

Keyword(s):

Sexual Differentiation ◽

Sex Chromosome ◽

Chromosome Complement ◽

Gonadal Hormones ◽

Steroid Synthesis

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Q-BANDING OF CHROMOSOMES IN HUMAN SPONTANEOUS ABORTIONS

Canadian Journal of Genetics and Cytology ◽

10.1139/g78-048 ◽

1978 ◽

Vol 20 (3) ◽

pp. 415-425 ◽

Cited By ~ 20

Author(s):

David H. Carr ◽

Milan M. Gedeon

Keyword(s):

Sex Ratio ◽

Sex Chromosomes ◽

Trisomy 21 ◽

Sex Chromosome ◽

Chromosome Complement ◽

Ring Chromosome ◽

Banding Technique ◽

Spontaneous Abortions ◽

Chromosome Anomalies ◽

Chromosome 13

Chromosome studies of 242 spontaneous abortions were carried out by Q-banding technique. The abortuses were selected for study because they were phenotypically abnormal, had not progressed beyond 12 weeks development, or were from women with repeated abortions. Chromosome anomalies were found in 126 (52%) of the abortuses. Of these, 71 (56%) were trisomies. Trisomies were found for all the autosomes except Nos. 1, 3, 5, 11, 17 and 18. Triploidy was the second commonest anomaly in this series, making up 26 (21%) of the total anomalies. About 70% of these had an XXY sex chromosome complement. Only 16 (13%) of the abortuses had X monosomy, a lower frequency than would be expected in an unselected study. Tetraploidy was found in 8 abortuses and the 5 remaining specimens had various anomalies. These included 3 translocations, a trisomy 21,X monosomy and a ring chromosome 13. Except for the greater frequency of XXY than XXX sex chromosomes in the triploids, there was no evidence of a distortion of the sex ratio, either among the trisomic or among the chromosomally normal abortuses.

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Sex biased expression of hormone related genes at early stage of sex differentiation in papaya flowers

Horticulture Research ◽

10.1038/s41438-021-00581-4 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Juan Liu ◽

Li-Yu Chen ◽

Ping Zhou ◽

Zhenyang Liao ◽

Hai Lin ◽

...

Keyword(s):

Transcription Factors ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Early Stage ◽

Sex Differentiation ◽

Molecular Genetic ◽

Morphological Difference ◽

Gene Interaction ◽

Development Stage ◽

Male And Female

AbstractSex types of papaya are controlled by a pair of nascent sex chromosomes, but molecular genetic mechanisms of sex determination and sex differentiation in papaya are still unclear. We performed comparative analysis of transcriptomic profiles of male and female floral buds at the early development stage before the initiation of reproductive organ primordia at which there is no morphological difference between male and female flowers. A total of 1734 differentially expressed genes (DEGs) were identified, of which 923 showed female-biased expression and 811 showed male-biased expression. Functional annotation revealed that genes related to plant hormone biosynthesis and signaling pathways, especially in abscisic acid and auxin pathways, were overrepresented in the DEGs. Transcription factor binding motifs, such as MYB2, GAMYB, and AP2/EREBP, were enriched in the promoters of the hormone-related DEGs, and transcription factors with those motifs also exhibited differential expression between sex types. Among these DEGs, we also identified 11 genes in the non-recombining region of the papaya sex chromosomes and 9 genes involved in stamen and carpel development. Our results suggested that sex differentiation in papaya may be regulated by multiple layers of regulation and coordination and involved transcriptional, epigenetic, and phytohormone regulation. Hormones, especially ABA and auxin, transcription factors, and genes in the non-recombination region of the sex chromosome could be involved in this process. Our findings may facilitate the elucidation of signal transduction and gene interaction in sex differentiation of unisexual flowers in papaya.

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Sleep Deprivation alters the influence of biological sex on active-phase sleep behavior

10.1101/2020.02.21.958231 ◽

2020 ◽

Author(s):

India Nichols ◽

Scott Vincent ◽

September Hesse ◽

J. Christopher Ehlen ◽

Allison Brager ◽

...

Keyword(s):

Sex Differences ◽

Sex Chromosomes ◽

Sex Chromosome ◽

Chromosome Complement ◽

Active Phase ◽

Sleep Loss ◽

Model Systems ◽

Poor Sleep ◽

Biological Sex ◽

Sleep Amount

AbstractPoor sleep is a hazard of daily life that oftentimes cannot be avoided. Gender differences in daily sleep and wake patterns are widely reported; however, it remains unclear how biological sex, which is comprised of genetic and endocrine components, directly influences sleep regulatory processes. In the majority of model systems studied thus far, sex differences in daily sleep amount are predominant during the active (wake) phase of the sleep-wake cycle. The pervasiveness of sex differences in sleep amount throughout phylogeny suggests a strong underlying genetic component. The goal of the current study is to determine if sex differences in active-phase sleep amount are dependent on sex chromosomes in mice.Sleep was examined in the four-core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of sex phenotype (male or female). In this line, sex phenotype is determined by the presence or absence of the Sry gene, which is dissociated from the Y chromosome. Polysomnographic sleep recordings were obtained from gonadectomized (GDX) FCG mice to examine spontaneous sleep states and the ability to recover from sleep loss. We report that during the active-phase, the presence of the Sry gene accounts for most sex differences during spontaneous sleep; however, during recovery from sleep loss, sex differences in sleep amount are partially driven by sex chromosome complement. These results suggest that genetic factors on the sex chromosomes encode the homeostatic response to sleep loss.

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