Promoting the understanding of sex differences to enhance equity and excellence in biomedical science

AbstractFrom the moment of our conception, each of us has a sex. Sex has a major role in determining the physical attributes of our bodies, the structure of our brains, our behavioral tendencies, our susceptibility and reaction to diseases, the environment in which we grow up, our place in society, the attitudes of others towards us, and our conception of self. Although sex may be considered to be determined primarily biologically, our gender (i.e., the social perception and implications of our sex) is arguably equally or more important for our lives. Sex and gender differences are created by an intricate reciprocal interaction of numerous biological and environmental forces

Metabolic impact of sex chromosomes.

Obesity and associated metabolic diseases are sexually dimorphic. To provide better diagnosis and treatment for both sexes, it is of interest to identify the factors that underlie male/female differences in obesity. Traditionally, sexual dimorphism has been attributed to effects of gonadal hormones, which influence numerous metabolic processes. However, the XX/XY sex chromosome complement is an additional factor that may play a role. Recent data using the four core genotypes mouse model have revealed that sex chromosome complement-independently from gonadal sex-plays a role in adiposity, feeding behavior, fatty liver and glucose homeostasis. Potential mechanisms for the effects of sex chromosome complement include differential gene dosage from X chromosome genes that escape inactivation, and distinct genomic imprints on X chromosomes inherited from maternal or paternal parents. Here we review recent data in mice and humans concerning the potential impact of sex chromosome complement on obesity and metabolic disease

Regional differences in dosage compensation on the chicken Z chromosome

Microarray data analysis revealed a cluster of well compensated genes in the MHM (male-hypermethylated) region on chicken chromosome Zp, whereas Zq is enriched in non-compensated genes. The non-coding MHM RNA may therefore play a role in dosage compensation in the female

Disruption of FEM1C-W gene in zebra finch: evolutionary insights on avian ZW genes

Sex chromosome genes control sex determination and differentiation, but the mechanisms of sex determination in birds are unknown. In this study, we analyzed the gene FEM1C which is highly conserved from Caenorhabditis elegans to higher vertebrates and interacts with the sex determining pathway in C. elegans. We found that FEM1C is located on the Z and W chromosome of zebra finches and probably other Passerine birds, but shows only Z linkage in other avian orders. In the zebra finch, FEM1C-W is degraded because of a point mutation and possibly because of loss of the first exon containing the start methionine. Thus, FEM1C-W appears to have degenerated or been lost from most bird species. FEM1C-Z is expressed in a cytoplasmic location in zebra finch fibroblast cells, as in C. elegans. FEM1C represents an interesting example of evolutionary degradation of a W chromosome gene

Metabolic impact of sex chromosomes

Obesity and associated metabolic diseases are sexually dimorphic. To provide better diagnosis and treatment for both sexes, it is of interest to identify the factors that underlie male/female differences in obesity. Traditionally, sexual dimorphism has been attributed to effects of gonadal hormones, which influence numerous metabolic processes. However, the XX/XY sex chromosome complement is an additional factor that may play a role. Recent data using the four core genotypes mouse model have revealed that sex chromosome complement—independently from gonadal sex—plays a role in adiposity, feeding behavior, fatty liver and glucose homeostasis. Potential mechanisms for the effects of sex chromosome complement include differential gene dosage from X chromosome genes that escape inactivation, and distinct genomic imprints on X chromosomes inherited from maternal or paternal parents. Here we review recent data in mice and humans concerning the potential impact of sex chromosome complement on obesity and metabolic disease

Finite Temperature Effective Potential for the Abelian Higgs Model to the Order e4,λ2e^4,\lambda^2

A complete calculation of the finite temperature effective potential for the abelian Higgs model to the order $e^4,\lambda^2$ is presented and the result is expressed in terms of physical parameters defined at zero temperature. The absence of a linear term is verified explicitly to the given order and proven to survive to all orders. The first order phase transition has weakened in comparison with lower order calculation, which shows up in a considerable decrease of the surface tension. The only difference from the original version is the splitting of some overlong lines causing problems with certain mailers.Comment: 13 pages LaTex ( figures not included , hardcopy available on request : [email protected] or t00heb@dhhdesy3 ) , DESY 93-08

Cell-autonomous sex determination outside of the gonad

The classic model of sex determination in mammals states that the sex of the individual is determined by the type of gonad that develops, which in turn determines the gonadal hormonal milieu that creates sex differences outside of the gonads. However, XX and XY cells are intrinsically different because of the cell-autonomous sex-biasing action of X and Y genes. Results: Recent studies of mice, in which sex chromosome complement is independent of gonadal sex, reveal that sex chromosome complement has strong effects contributing to sex differences in phenotypes such as metabolism. Adult mice with two X chromosomes (relative to mice with one X chromosome) show dramatically greater increases in body weight and adiposity after gonadectomy, irrespective of their gonadal sex. When fed a high-fat diet, XX mice develop striking hyperinsulinemia and fatty liver, relative to XY mice. The sex chromosome effects are modulated by the presence of gonadal hormones, indicating an interaction of the sex-biasing effects of gonadal hormones and sex chromosome genes. Conclusions: Other cell-autonomous sex chromosome effects are detected in mice in many phenotypes. Birds (relative to eutherian mammals) are expected to show more widespread cell-autonomous sex determination in non-gonadal tissues, because of ineffective sex chromosome dosage compensation mechanisms

Zebra finch cell lines from naturally occurring tumors

The zebra finch (Taeniopygia guttata) has been intensively studied in many research fields including neuroscience, behavioral neurobiology, and evolution of the genome. Although numerous molecular and genomic resources are available for this model species, immortalized cell lines have been lacking. We have established two zebra finch cell lines derived from spontaneous tumors. ZFTMA is a tetraploid female cell line and G266 as a diploid male cell line. These first zebra finch cell lines should facilitate development of research on this model species

Sex differences in renal angiotensin converting enzyme 2 (ACE2) activity are 17β-oestradiol-dependent and sex chromosome-independent

<p>Abstract</p> <p>Background</p> <p>Angotensin converting enzyme 2 (ACE2) is a newly discovered monocarboxypeptidase that counteracts the vasoconstrictor effects of angiotensin II (Ang II) by converting Ang II to Ang-(1-7) in the kidney and other tissues.</p> <p>Methods</p> <p>ACE2 activity from renal homogenates was investigated by using the fluorogenic peptide substrate Mca-YVADAPK(Dnp)-OH, where Mca is (7-methoxycoumarin-4-yl)-acetyl and Dnp is 2,4-dinitrophenyl.</p> <p>Results</p> <p>We found that ACE2 activity expressed in relative fluorescence units (RFU) in the MF1 mouse is higher in the male (M) compared to the female (F) kidney [ACE2 (RFU/min/μg protein): M 18.1 ± 1.0 versus F 11.1 ± 0.39; <it>P </it>< 0.0001; <it>n </it>= 6]. Substrate concentration curves revealed that the higher ACE2 activity in the male was due to increased ACE2 enzyme velocity (V_max) rather than increased substrate affinity (K_m). We used the four core genotypes mouse model in which gonadal sex (ovaries versus testes) is separated from the sex chromosome complement enabling comparisons among XX and XY gonadal females and XX and XY gonadal males. Renal ACE2 activity was greater in the male than the female kidney, regardless of the sex chromosome complement [ACE2 (RFU/min/μg protein): intact-XX-F, 7.59 ± 0.37; intact-XY-F, 7.43 ± 0.53; intact-XX-M, 12.1 ± 0.62; intact-XY-M, 12.7 ± 1.5; <it>n </it>= 4-6/group; <it>P </it>< 0.0001, F versus M, by two-way ANOVA]. Enzyme activity was increased in gonadectomized (GDX) female mice regardless of the sex chromosome complement whereas no effect of gonadectomy was observed in the males [ACE2 (RFU/min/μg protein): GDX-XX-F, 12.4 ± 1.2; GDX-XY-F, 11.1 ± 0.76; GDX-XX-M, 13.2 ± 0.97; GDX-XY-M, 11.6 ± 0.81; <it>n </it>= 6/group]. 17β-oestradiol (E₂) treatment of GDX mice resulted in ACE2 activity that was only 40% of the activity found in the GDX mice, regardless of their being male or female, and was independent of the sex chromosome complement [ACE2 (RFU/min/μg protein): GDX+E₂-XX-F, 5.56 ± 1.0; GDX+E₂-XY-F, 4.60 ± 0.52; GDX+E₂-XX-M, 5.35 ± 0.70; GDX+E₂-XY-M, 5.12 ± 0.47; <it>n </it>= 6/group].</p> <p>Conclusions</p> <p>Our findings suggest sex differences in renal ACE2 activity in intact mice are due, at least in part, to the presence of E₂in the ovarian hormone milieu and not to the testicular milieu or to differences in sex chromosome dosage (2X versus 1X; 0Y versus 1Y). E₂regulation of renal ACE2 has particular implications for women across their life span since this hormone changes radically during puberty, pregnancy and menopause.</p