Cell‐autonomous sex determination outside of the gonad

Arnold, Arthur P.; Chen, Xuqi; Link, Jenny; Itoh, Yuichiro; Reue, Karen

doi:10.1002/dvdy.23936

Cited by 66 publications

(56 citation statements)

References 79 publications

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“…Because this is a relative comparison, a gene on non-PAR Y could lead to more neurodegeneration or a gene on non-PAR X could lead to CNS resilience. The first possibility is somewhat unlikely, as there are very few genes on non-PAR Y that relate to processes other than reproduction and most sex chromosome effects published to date are X chromosome effects (37,38).…”

Section: Discussionmentioning

confidence: 99%

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

Itoh²,

Askarinam³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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111

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Women are more susceptible to multiple sclerosis (MS) and have more robust immune responses than men. However, men with MS tend to demonstrate a more progressive disease course than women, suggesting a disconnect between the severity of an immune attack and the CNS response to a given immune attack. We have previously shown in an MS model, experimental autoimmune encephalomyelitis, that autoantigen-sensitized XX lymph node cells, compared with XY, are more encephalitogenic. These studies demonstrated an effect of sex chromosomes in the induction of immune responses, but did not address a potential role of sex chromosomes in the CNS response to immunemediated injury. Here, we examined this possibility using XX versus XY bone marrow chimeras reconstituted with a common immune system of one sex chromosomal type. We found that experimental autoimmune encephalomyelitis mice with an XY sex chromosome complement in the CNS, compared with XX, demonstrated greater clinical disease severity with more neuropathology in the spinal cord, cerebellum, and cerebral cortex. A candidate gene on the X chromosome, toll-like receptor 7, was then examined. Toll-like receptor 7 expression in cortical neurons was higher in mice with XY compared with mice with XX CNS, consistent with the known neurodegenerative role for toll-like receptor 7 in neurons. These results suggest that sex chromosome effects on neurodegeneration in the CNS run counter to effects on immune responses, and may bear relevance to the clinical enigma of greater MS susceptibility in women but faster disability progression in men. This is a demonstration of a direct effect of sex chromosome complement on neurodegeneration in a neurological disease.sex differences | XY genes | Tlr7

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Section: Discussionmentioning

confidence: 99%

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

Itoh²,

Askarinam³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

111

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“…Biological sex differences derive from two evolutionary forces: natural selection, due to the different biological roles of males and females, and sexual selection, due to competition for mates. The proximal causes of biological sex differences comprise a complex interplay of genetic and endocrine mechanisms (9,10,32,271,425,466,471,671,807). In most mammals, the development of phenotypic sex differences is initiated by genes on the X and Y sex chromosomes, with females typically possessing the XX karyotype and males, the XY karyotype.…”

Section: Physiological Sex Differences In Disordered Eating)mentioning

confidence: 99%

Sex differences in the physiology of eating

Asarian

Geary²

2013

American Journal of Physiology-Regulatory, Integrative and Comp

414

349

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(HPG) axis function fundamentally affects the physiology of eating. We review sex differences in the physiological and pathophysiological controls of amounts eaten in rats, mice, monkeys, and humans. These controls result from interactions among genetic effects, organizational effects of reproductive hormones (i.e., permanent early developmental effects), and activational effects of these hormones (i.e., effects dependent on hormone levels). Male-female sex differences in the physiology of eating involve both organizational and activational effects of androgens and estrogens. An activational effect of estrogens decreases eating 1) during the periovulatory period of the ovarian cycle in rats, mice, monkeys, and women and 2) tonically between puberty and reproductive senescence or ovariectomy in rats and monkeys, sometimes in mice, and possibly in women. Estrogens acting on estrogen receptor-␣ (ER␣) in the caudal medial nucleus of the solitary tract appear to mediate these effects in rats. Androgens, prolactin, and other reproductive hormones also affect eating in rats. Sex differences in eating are mediated by alterations in orosensory capacity and hedonics, gastric mechanoreception, ghrelin, CCK, glucagon-like peptide-1 (GLP-1), glucagon, insulin, amylin, apolipoprotein A-IV, fatty-acid oxidation, and leptin. The control of eating by central neurochemical signaling via serotonin, MSH, neuropeptide Y, Agouti-related peptide (AgRP), melanin-concentrating hormone, and dopamine is modulated by HPG function. Finally, sex differences in the physiology of eating may contribute to human obesity, anorexia nervosa, and binge eating. The variety and physiological importance of what has been learned so far warrant intensifying basic, translational, and clinical research on sex differences in eating.neuroendocrinology; estrogens; testosterone; eating disorders; obesity SEX DIFFERENCES ARE PERVASIVE in physiology and medicine (51,64,73,109,110,466,797,826). The controls of eating and energy homeostasis are no exceptions. It was observed approximately 100 years ago that removal of the ovaries leads to marked accretion of adipose tissue in rats (697), that daily food intake expressed as kilocalories per gram body weight differs between male and female rats (778), and that food intake varies regularly through the ovarian cycle in intact female rats (674, 779). Sex differences in eating have been the subject of physiological research ever since. The clinical relevance of this work is increasingly evident. In the United States, women are approximately threefold more vulnerable than men to psychiatric eating disorders (346,351) and approximately twofold more vulnerable to severe and morbid obesity (BMI Ն 35 and 40 kg/m 2 , respectively, mass/height 2 ) (226). Women also appear to suffer more from these disorders in terms of physical and psychological functioning and quality of life (24,84,273,292,465,531,762). The increased obesity burden suffered by women is reflected in the fact that Ͼ80% of bariatric surgery patients in the U...

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“…To date, we do not assess sex, ie, genes and hormones, but rather use the sex categories (female and male) as a proxy of sex (Maney, 2016). This is however a very poor proxy because it does not capture the interactions between the different components of sex (eg, Arnold et al, 2013) nor their dynamic and reactive aspects (eg, the wide fluctuations in the level of the three main gonadal hormones, estradiol, progesterone, and testosterone, within individuals of both sex categories as a function of multiple factors, including environmental (eg, time of day) and social (eg, status;van Anders et al, 2014)). Future studies would hopefully advance our understanding of these aspects of sex, and lead to the development of methods for incorporating measures of sex into studies of brain and behavior.…”

Section: Joelmentioning

confidence: 99%

Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?

Joel

McCarthy

2016

Neuropsychopharmacol

140

113

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Understanding the multiplicity of ways in which sex can alter the brain is essential to crafting policies and treatments that are beneficial for all human beings. This is particularly true for the field of neuropsychopharmacology, as many neuropsychiatric disorders exhibit gender bias in the frequency, severity, or response to treatment. The goal of this circumspective is to provide two views on the current state of the art of the relations between sex and the brain, relations that are studied almost exclusively by comparing females and males on specific end points, from gene expression to behavior. We start by suggesting a framework for defining what is being measured and what it means. We suggest that 'sex differences' can be classified on four dimensions: (1) persistent vs transient across the lifespan; (2) context independent vs dependent; (3) dimorphic vs continuous; and (4) a direct vs an indirect consequence of sex. To accurately classify a sex difference along these dimensions, one may need to compare females and males under varied conditions. We next discuss current data on the mechanisms of sexual differentiation of the brain and on sex differences in the brain to conclude that the brain of each male and female is a mosaic of relative masculinization, feminization, and sameness, which theoretically could produce an infinite variety of individuals. We also raise the possibility that sex differences in the brain are canalized, which may act to both enhance and restrain variation between males and females. We end by discussing ways to consider sex when studying neuropsychiatric disorders.

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Cell‐autonomous sex determination outside of the gonad

Cited by 66 publications

References 79 publications

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis

Sex differences in the physiology of eating

Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?

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