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What a Difference an X or Y Makes: Sex Chromosomes, Gene Dose, and Epigenetics in Sexual Differentiation

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Sex and Gender Differences in Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 214))

Abstract

A modern general theory of sex determination and sexual differentiation identifies the factors that cause sexual bias in gene networks, leading to sex differences in physiology and disease. The primary sex-biasing factors are those encoded on the sex chromosomes that are inherently different in the male and female zygotes. These factors, and downstream factors such as gonadal hormones, act directly on tissues to produce sex differences and antagonize each other to reduce sex differences. Recent studies of mouse models such as the four core genotypes have begun to distinguish between the direct effects of sex chromosome complement (XX vs. XY) and hormonal effects. Several lines of evidence implicate epigenetic processes in the control of sex differences, although a great deal of information is needed about sex differences in the epigenome.

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Abbreviations

EAE:

Experimental autoimmune encephalomyelitis

FCG:

Four core genotypes

Kdm5c:

lysine (K)-specific demethylase 5C

Kdm6a:

lysine (K)-specific demethylase 6A

Sry:

Sex determining region, Y chromosome

Sf1:

Steroidogenic factor one, also known as Nr5a1

Trp53:

Transformation related protein 53, encodes the p53 protein

XXM:

XX gonadal male

XYM:

XY gonadal male

XXF:

XX gonadal female

XYF:

XY gonadal female

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Authors and Affiliations

  1. Laboratory of Neuroendocrinology of the Brain Research Institute, Department of Integrative Biology and Physiology, University of California, Terasaki Life Science Building, 610 Charles Young Drive South, Los Angeles, CA, 90095, USA

    Arthur P. Arnold, Xuqi Chen & Yuichiro Itoh

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  1. Arthur P. Arnold
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  2. Xuqi Chen
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  3. Yuichiro Itoh
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Correspondence to Arthur P. Arnold .

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Editors and Affiliations

  1. Institute of Gender in Medicine (GiM), Center for Cardiovascular Research (CCR), Charité - Universitätsmedizin Berlin, Hessische Str. 3-4, Berlin, 10115, Germany

    Vera Regitz-Zagrosek

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Arnold, A.P., Chen, X., Itoh, Y. (2013). What a Difference an X or Y Makes: Sex Chromosomes, Gene Dose, and Epigenetics in Sexual Differentiation. In: Regitz-Zagrosek, V. (eds) Sex and Gender Differences in Pharmacology. Handbook of Experimental Pharmacology, vol 214. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30726-3_4

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