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Reframing sexual differentiation of the brain

Nature Neuroscience volume 14, pages 677–683 (2011)Cite this article

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Abstract

In the twentieth century, the dominant model of sexual differentiation stated that genetic sex (XX versus XY) causes differentiation of the gonads, which then secrete gonadal hormones that act directly on tissues to induce sex differences in function. This serial model of sexual differentiation was simple, unifying and seductive. Recent evidence, however, indicates that the linear model is incorrect and that sex differences arise in response to diverse sex-specific signals originating from inherent differences in the genome and involve cellular mechanisms that are specific to individual tissues or brain regions. Moreover, sex-specific effects of the environment reciprocally affect biology, sometimes profoundly, and must therefore be integrated into a realistic model of sexual differentiation. A more appropriate model is a parallel-interactive model that encompasses the roles of multiple molecular signals and pathways that differentiate males and females, including synergistic and compensatory interactions among pathways and an important role for the environment.

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Figure 1: Twentieth-century linear view of sexual differentiation.
Figure 2: Genetics matter.
Figure 3: Multiple mechanisms of estradiol-induced differentiation.
Figure 4: Redefining sexual differentiation.

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References

  1. Cahill, L. Why sex matters for neuroscience. Nat. Rev. Neurosci. 7, 477–484 (2006).

    Article  CAS  PubMed  Google Scholar 

  2. Mogil, J.S. & Chanda, M.L. The case for the inclusion of female subjects in basic science studies of pain. Pain 117, 1–5 (2005).

    PubMed  Google Scholar 

  3. Voskuhl, R. Sex differences in autoimmune diseases. Biol. Sex Differ. 2, 1 (2011).

    PubMed  PubMed Central  Google Scholar 

  4. Swaab, D.F. & Hofman, M.A. Sexual differentiation of the human hypothalamus in relation to gender and sexual orientation. Trends Neurosci. 18, 264–270 (1995).

    CAS  PubMed  Google Scholar 

  5. McCarthy, M., De Vries, G. & Forger, N. in Hormones, Brain and Behavior, Vol. 3 (eds. Pfaff, D.W., Arnold, A.P., Etgen, A.M., Fahrbach, S.E. & Rubin, R.T.) Ch. 17, 1707–1744 (Academic Press, 2009).

  6. Amateau, S.K. & McCarthy, M.M. Induction of PGE(2) by estradiol mediates developmental masculinization of sex behavior. Nat. Neurosci. 7, 643–650 (2004).

    CAS  PubMed  Google Scholar 

  7. Schwarz, J.M., Liang, S.-L., Thompson, S.M. & McCarthy, M.M. Estradiol induces hypothalamic dendritic spines by enhancing glutamate release: a mechanism for organizational sex differences. Neuron 58, 584–598 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Park, J.H., Bonthius, P.J., Tsai, H.W., Bekiranov, S. & Rissman, E.F. Amyloid beta precursor protein regulates male sexual behavior. J. Neurosci. 30, 9967–9972 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Beery, A.K. & Zucker, I. Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 35, 565–572 (2011).

    PubMed  Google Scholar 

  10. Jazin, E. & Cahill, L. Sex differences in molecular neuroscience: from fruit flies to humans. Nat. Rev. Neurosci. 11, 9–17 (2010).

    CAS  PubMed  Google Scholar 

  11. De Vries, G.J. Minireview: Sex differences in adult and developing brains: compensation, compensation, compensation. Endocrinology 145, 1063–1068 (2004).

    CAS  PubMed  Google Scholar 

  12. Arnold, A.P. & Chen, X. What does the “four core genotypes” mouse model tell us about sex differences in the brain and other tissues? Front. Neuroendocrinol. 30, 1–9 (2009).

    PubMed  Google Scholar 

  13. Szyf, M., McGowan, P. & Meaney, M.J. The social environment and the epigenome. Environ. Mol. Mutagen. 49, 46–60 (2008).

    CAS  PubMed  Google Scholar 

  14. Phoenix, C.H., Goy, R.W., Gerall, A.A. & Young, W.C. Organizing action of prenatally administered testosterone proprionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65, 369–382 (1959).

    CAS  PubMed  Google Scholar 

  15. Arnold, A.P. The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm. Behav. 55, 570–578 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Sisk, C.L. & Zehr, J.L. Pubertal hormones organize the adolescent brain and behavior. Front. Neuroendocrinol. 26, 163–174 (2005).

    CAS  PubMed  Google Scholar 

  17. Zhao, D. et al. Somatic sex identity is cell autonomous in the chicken. Nature 464, 237–242 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Goodfellow, P.N. & Lovell-Badge, R. SRY and sex determination in mammals. Annu. Rev. Genet. 27, 71–92 (1993).

    CAS  PubMed  Google Scholar 

  19. Dewing, P. et al. Direct regulation of adult brain function by the male-specific factor SRY. Curr. Biol. 16, 415–420 (2006).

    CAS  PubMed  Google Scholar 

  20. Becker, J.B., Molenda, H. & Hummer, D.L. Gender differences in the behavioral responses to cocaine and amphetamine. Implications for mechanisms mediating gender differences in drug abuse. Ann. NY Acad. Sci. 937, 172–187 (2001).

    CAS  PubMed  Google Scholar 

  21. McCarthy, M.M. & Konkle, A.T. When is a sex difference not a sex difference? Front. Neuroendocrinol. 26, 85–102 (2005).

    CAS  PubMed  Google Scholar 

  22. Chang, S.C., Tucker, T., Thorogood, N.P. & Brown, C.J. Mechanisms of X-chromosome inactivation. Front. Biosci. 11, 852–866 (2006).

    CAS  PubMed  Google Scholar 

  23. Migeon, B.R. Females are Mosaic: X Inactivation and Sex Differences in Disease (Oxford University Press, 2007).

  24. Arnold, A.P. Sex chromosomes and brain gender. Nat. Rev. Neurosci. 5, 701–708 (2004).

    CAS  PubMed  Google Scholar 

  25. Arnold, A.P. Mouse models for evaluating sex chromosome effects that cause sex differences in non-gonadal tissues. J. Neuroendocrinol. 21, 377–386 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Majdic, G. & Tobet, S. Cooperation of sex chromosomal genes and endocrine influences for hypothalamic sexual differentiation. Front. Neuroendocrinol. published online, doi:10.1016/j.yfrne.2011.02.009 (19 February 2011).10.1016/j.yfrne.2011.02.009

  27. De Vries, G.J. et al. A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J. Neurosci. 22, 9005–9014 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Arnold, A.P. et al. Minireview: Sex chromosomes and brain sexual differentiation. Endocrinology 145, 1057–1062 (2004).

    CAS  PubMed  Google Scholar 

  29. Gatewood, J.D. et al. Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice. J. Neurosci. 26, 2335–2342 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Gioiosa, L., Chen, X., Watkins, R., Umeda, E.A. & Arnold, A.P. Sex chromosome complement affects nociception and analgesia in newborn mice. J. Pain 9, 962–969 (2008).

    PubMed  PubMed Central  Google Scholar 

  31. Gioiosa, L. et al. Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice. Horm. Behav. 53, 124–130 (2008).

    CAS  PubMed  Google Scholar 

  32. Quinn, J.J., Hitchcott, P.K., Umeda, E.A., Arnold, A.P. & Taylor, J.R. Sex chromosome complement regulates habit formation. Nat. Neurosci. 10, 1398–1400 (2007).

    CAS  PubMed  Google Scholar 

  33. Barker, J.M., Torregrossa, M.M., Arnold, A.P. & Taylor, J.R. Dissociation of genetic and hormonal influences on sex differences in alcoholism-related behaviors. J. Neurosci. 30, 9140–9144 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen, X. et al. Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes. Dev. Neurobiol. 68, 265–273 (2008).

    CAS  PubMed  Google Scholar 

  35. Smith-Bouvier, D.L. et al. A role for sex chromosome complement in the female bias in autoimmune disease. J. Exp. Med. 205, 1099–1108 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Cox, K.H. & Rissman, E.F. Sex differences in juvenile mouse social behavior are influenced by sex chromosomes and social context. Genes Brain Behav. published online, doi:10.1111/j.1601-183X.2011.00688.x (17 March 2011).10.1111/j.1601-183X.2011.00688.x

  37. McPhie-Lalmansingh, A.A., Tejada, L.D., Weaver, J.L. & Rissman, E.F. Sex chromosome complement affects social interactions in mice. Horm. Behav. 54, 565–570 (2008).

    PubMed  PubMed Central  Google Scholar 

  38. Chen, X., Grisham, W. & Arnold, A.P. X chromosome number causes sex differences in gene expression in adult mouse striatum. Eur. J. Neurosci. 29, 768–776 (2009).

    PubMed  Google Scholar 

  39. van Nas, A. et al. Elucidating the role of gonadal hormones in sexually dimorphic gene coexpression networks. Endocrinology 150, 1235–1249 (2009).

    CAS  PubMed  Google Scholar 

  40. Abel, J.M., Witt, D.M. & Rissman, E.F. Sex differences in the cerebellum and frontal cortex: roles of estrogen receptor alpha and sex chromosome genes. Neuroendocrinology published online, doi:10.1159/000324402 (16 February 2011).10.1159/000324402

  41. Davies, W., Isles, A.R., Burgoyne, P.S. & Wilkinson, L.S. X-linked imprinting: effects on brain and behavior. Bioessays 28, 35–44 (2006).

    CAS  PubMed  Google Scholar 

  42. Gregg, C., Zhang, J., Butler, J.E., Haig, D. & Dulac, C. Sex-specific parent-of-origin allelic expression in the mouse brain. Science 329, 682–685 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. McCarthy, M.M. Estradiol and the developing brain. Physiol. Rev. 88, 91–124 (2008).

    CAS  PubMed  Google Scholar 

  44. Ogawa, S. et al. Roles of estrogen receptor-α gene expression in reproduction-related behaviors in female mice. Endocrinology 139, 5070–5081 (1998).

    CAS  PubMed  Google Scholar 

  45. Ogawa, S. et al. Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO). Proc. Natl. Acad. Sci. USA 97, 14737–14741 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Kudwa, A.E., Bodo, C., Gustafsson, J.A. & Rissman, E.F. A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior. Proc. Natl. Acad. Sci. USA 102, 4608–4612 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Honda, S., Harada, N., Ito, S., Takagi, Y. & Maeda, S. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. Biochem. Biophys. Res. Commun. 252, 445–449 (1998).

    CAS  PubMed  Google Scholar 

  48. Bakker, J., Honda, S., Harada, N. & Balthazart, J. The aromatase knockout (ArKO) mouse provides new evidence that estrogens are required for the development of the female brain. Ann. NY Acad. Sci. 1007, 251–262 (2003).

    CAS  PubMed  Google Scholar 

  49. Bakker, J. & Brock, O. Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development. J. Neuroendocrinol. 22, 728–735 (2010).

    CAS  PubMed  Google Scholar 

  50. Juntti, S.A., Coats, J.K. & Shah, N.M. A genetic approach to dissect sexually dimorphic behaviors. Horm. Behav. 53, 627–637 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Juntti, S.A. et al. The androgen receptor governs the execution, but not programming, of male sexual and territorial behaviors. Neuron 66, 260–272 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Matsumoto, A. Sexual Differentiation of the Brain (CRC Press, 2000).

  53. Morris, J.A., Jordan, C.L. & Breedlove, S.M. Sexual differentiation of the vertebrate nervous system. Nat. Neurosci. 7, 1034–1039 (2004).

    CAS  PubMed  Google Scholar 

  54. Forger, N.G. et al. Deletion of Bax eliminates sex differences in the mouse forebrain. Proc. Natl. Acad. Sci. USA 101, 13666–13671 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Waters, E.M. & Simerly, R.B. Estrogen induces caspase-dependent cell death during hypothalamic development. J. Neurosci. 29, 9714–9718 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Krishnan, S., Intlekofer, K.A., Aggison, L.K. & Petersen, S.L. Central role of TRAF-interacting protein in a new model of brain sexual differentiation. Proc. Natl. Acad. Sci. USA 106, 16692–16697 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Simerly, R.B. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu. Rev. Neurosci. 25, 507–536 (2002).

    CAS  PubMed  Google Scholar 

  58. Zhang, J.-M., Konkle, A.T.M., Zup, S.L. & McCarthy, M.M. Impact of sex and hormones on new cells in the developing rat hippocampus: a novel source of sex dimorphism? Eur. J. Neurosci. 27, 791–800 (2008).

    PubMed  PubMed Central  Google Scholar 

  59. Bowers, J., Waddell, J. & McCarthy, M. A developmental sex difference in hippocampal neurogenesis is mediated by endogenous estradiol. Biol. Sex Differ. 1, 8 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Isgor, C. & Sengelaub, D.R. Prenatal gonadal steroids affect adult spatial behavior, CA1 and CA3 pyramidal cell morphology in rats. Horm. Behav. 34, 183–198 (1998).

    CAS  PubMed  Google Scholar 

  61. Krebs-Kraft, D.L., Hill, M.N., Hillard, C.J. & McCarthy, M.M. Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior. Proc. Natl. Acad. Sci. USA 107, 20535–20540 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. de Vries, G.J. et al. Sexual differentiation of vasopressin innervation of the brain: cell death versus phenotypic differentiation. Endocrinology 149, 4632–4637 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Mong, J.A., Glaser, E. & McCarthy, M.M. Gonadal steroids promote glial differentiation and alter neuronal morphology in the developing hypothalamus in a regionally specific manner. J. Neurosci. 19, 1464–1472 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Todd, B.J., Schwarz, J.M., Mong, J.A. & McCarthy, M.M. Glutamate AMPA/kainate receptors, not GABAA receptors, mediate estradiol-induced sex differences in the hypothalamus. Dev. Neurobiol. 67, 304–315 (2007).

    CAS  PubMed  Google Scholar 

  65. Wright, C.L., Burks, S.R. & McCarthy, M.M. Identification of prostaglandin E2 receptors mediating perinatal masculinization of adult sex behavior and neuroanatomical correlates. Dev. Neurobiol. 68, 1406–1419 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Wright, C.L. & McCarthy, M.M. Prostaglandin E2-induced masculinization of brain and behavior requires protein kinase A, AMPA/kainate and metabotropic glutamate receptor signaling. J. Neurosci. 29, 13274–13282 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Mong, J.A., Nunez, J.L. & McCarthy, M.M. GABA mediates steroid-induced astrocyte differentiation in the neonatal rat hypothalamus. J. Neuroendocrinol. 14, 45–55 (2002).

    CAS  PubMed  Google Scholar 

  68. Schwarz, J.M. & McCarthy, M.M. The role of neonatal NMDA receptor activation in defeminization and masculinization of sex behavior in the rat. Horm. Behav. 54, 662–668 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Herrmann, K. & Arnold, A.P. Lesions of HVc block the developmental masculinizing effects of estradiol in the female zebra finch song system. J. Neurobiol. 22, 29–39 (1991).

    CAS  PubMed  Google Scholar 

  70. Grisham, W., Mathews, G.A. & Arnold, A.P. Local intracerebral implants of estrogen masculinize some aspects of the zebra finch song system. J. Neurobiol. 25, 185–196 (1994).

    CAS  PubMed  Google Scholar 

  71. Beato, M. Gene regulation by steroid hormones. Cell 56, 335–344 (1989).

    CAS  PubMed  Google Scholar 

  72. Beato, M. & Klug, J. Steroid hormone receptors: an update. Hum. Reprod. Update 6, 225–236 (2000).

    CAS  PubMed  Google Scholar 

  73. Woolley, C.S. Acute effects of estrogen on neuronal physiology. Annu. Rev. Pharmacol. Toxicol. 47, 657–680 (2007).

    CAS  PubMed  Google Scholar 

  74. Balthazart, J. & Ball, G.F. Is brain estradiol a hormone or a neurotransmitter? Trends Neurosci. 29, 241–249 (2006).

    CAS  PubMed  Google Scholar 

  75. Remage-Healey, L., Maidment, N.T. & Schlinger, B.A. Forebrain steroid levels fluctuate rapidly during social interactions. Nat. Neurosci. 11, 1327–1334 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Petrosino, S. & Di Marzo, V. FAAH and MAGL inhibitors: therapeutic opportunities from regulating endocannabinoid levels. Curr. Opin. Investig. Drugs 11, 51–62 (2010).

    CAS  PubMed  Google Scholar 

  77. Hill, M.N. et al. Functional interactions between stress and the endocannabinoid system: from synaptic signaling to behavioral output. J. Neurosci. 30, 14980–14986 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Micevych, P., Kuo, J. & Christensen, A. Physiology of membrane oestrogen receptor signaling in reproduction. J. Neuroendocrinol. 21, 249–256 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Garcia-Segura, L.M., Lorenz, B. & DonCarlos, L.L. The role of glia in the hypothalamus: implications for gonadal steroid feedback and reproductive neuroendocrine output. Reproduction 135, 419–429 (2008).

    CAS  PubMed  Google Scholar 

  80. London, S.E., Remage-Healey, L. & Schlinger, B.A. Neurosteroid production in the songbird brain: a re-evaluation of core principles. Front. Neuroendocrinol. 30, 302–314 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Fausto-Sterling, A. Sexing the Body: Gender Politics and the Construction of Sexuality (Basic Books, 2000).

  82. Frome, P.M. & Eccles, J.S. Parents' influence on children's achievement-related perceptions. J. Pers. Soc. Psychol. 74, 435–452 (1998).

    CAS  PubMed  Google Scholar 

  83. Lippa, R.A. Sex differences in personality traits and gender-related occupational preferences across 53 nations: testing evolutionary and social-environmental theories. Arch. Sex. Behav. 39, 619–636 (2010).

    PubMed  Google Scholar 

  84. Champagne, F.A. Epigenetic mechanisms and the transgernational effects of maternal care. Front. Neuroendocrinol. 29, 386–397 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Moore, C.L. Maternal contributions to the development of masculine sexual behavior in laboratory rats. Dev. Psychobiol. 17, 347–356 (1984).

    CAS  PubMed  Google Scholar 

  86. Lenz, K.M. & Sengelaub, D.R. Maternal licking influences dendritic development of motoneurons in a sexually dimorphic neuromuscular system. Brain Res. 1092, 87–99 (2006).

    CAS  PubMed  Google Scholar 

  87. Kurian, J.R., Olesen, K.M. & Auger, A.P. Sex differences in epigenetic regulation of the estrogen receptor-alpha promoter within the developing preoptic area. Endocrinology 151, 2297–2305 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Westberry, J.M., Trout, A.L. & Wilson, M.E. Epigenetic regulation of estrogen receptor alpha gene expression in the mouse cortex during early postnatal development. Endocrinology 151, 731–740 (2010).

    CAS  PubMed  Google Scholar 

  89. Schwarz, J.M., Nugent, B.M. & McCarthy, M.M. Developmental and hormone-induced epigenetic changes to estrogen and progesterone receptor genes in brain are dynamic across the life span. Endocrinology 151, 4871–4881 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Tsai, H.W., Grant, P.A. & Rissman, E.F. Sex differences in histone modifications in the neonatal mouse brain. Epigenetics 4, 47–53 (2009).

    CAS  PubMed  Google Scholar 

  91. Murray, E.K., Hien, A., de Vries, G.J. & Forger, N.G. Epigenetic control of sexual differentiation of the bed nucleus of the stria terminalis. Endocrinology 150, 4241–4247 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. McCarthy, M.M. et al. The epigenetics of sex differences in the brain. J. Neurosci. 29, 12815–12823 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work on this manuscript was supported by grants MH52716 and NS050525 to M.M.M. and grants NS043196 and DC000217 to A.P.A.

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  1. Departments of Physiology and Psychiatry and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland, USA

    Margaret M McCarthy

  2. Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, California, USA

    Arthur P Arnold

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McCarthy, M., Arnold, A. Reframing sexual differentiation of the brain. Nat Neurosci 14, 677–683 (2011). https://doi.org/10.1038/nn.2834

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