A Sexually Dimorphic Nucleus in the Human Brain

Swaab, D.F.; Fliers, Eric

doi:10.1126/science.3992248

Cited by 482 publications

(173 citation statements)

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“…The fact that they could not find a sex difference in INAH1 (= SDN-POA), as found by us (63), could be fully explained by the strong age effect on the sex differences of this nucleus (58,65). In fact, the sex difference develops only after the age of 5 years and disappears temporarily after the age of 50 years (63,66,67 (63). Further analysis of INAH1 and 2 in the transsexual population is ongoing, and confirms the presence of a clear sex difference in adult controls up to 50 years of age.…”

Section: Sex Differences In the Human Brainmentioning

confidence: 52%

“…In the current review we focus on the sex differences in the human hypothalamus and adjacent areas. When observed by our group, the structural difference in the intermediate nucleus of the human hypothalamus (InM) (60-62) was at first termed "the sexually dimorphic nucleus of the preoptic area (SDN-POA)" (63). We found this nucleus to be 2.5 times larger in men than in women and to contain 2.2 times as many cells (63).…”

Section: Sex Differences In the Human Brainmentioning

confidence: 69%

“…When observed by our group, the structural difference in the intermediate nucleus of the human hypothalamus (InM) (60-62) was at first termed "the sexually dimorphic nucleus of the preoptic area (SDN-POA)" (63). We found this nucleus to be 2.5 times larger in men than in women and to contain 2.2 times as many cells (63). Allen et al, (64) described four interstitial nuclei of the anterior hypothalamus (INAH1-4) and found, in men compared to women, a larger volume of the INAH3 and INAH2 subdivisions (respectively 2.8 and 2 times greater).…”

Section: Sex Differences In the Human Brainmentioning

confidence: 99%

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Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Savić

Garcı́a-Falgueras

Swaab

2010

Progress in Brain Research

121

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SummaryDuring the intrauterine period the fetal brain develops in the male direction through a direct action of testosterone on the developing nerve cells, or in the female direction through the absence of this hormone surge. In this way, our gender identity (the conviction of belonging to the male or female gender) and sexual orientation are programmed into our brain structures when we are still in the womb. However, since sexual differentiation of the genitals takes place in the first two months of pregnancy and sexual differentiation of the brain starts in the second half of pregnancy, these two processes can be influenced independently, which may result in transsexuality. This also means that in the event of ambiguous sex at birth, the degree of masculinization of the genitals may not reflect the degree of masculinization of the brain. There is no proof that social environment after birth has an effect on gender identity or sexual orientation.KEY WORDS: gender identity, homosexuality, human brain, sexual orientation, sexual differentiation, transsexuality. Sexual organization and activation of the human brainThe process of sexual differentiation of the brain brings about permanent changes in brain structures and functions via interactions of the developing neurons with the environment, understood in its widest sense. The environment of a developing neuron is formed by the surrounding nerve cells and the child's circulating hormones, as well as the hormones, nutrients, medication and other chemical substances from the mother and the environment that enter the fetal circulation via the placenta. All these factors may have a lasting effect on the sexual differentiation of the brain. The testicles and ovaries develop in the sixth week of pregnancy. This occurs under the influence of a cascade of genes, starting with the sex-determining gene on the Y chromosome (SRY). The production of testosterone by a boy's testes is necessary for sexual differentiation of the sexual organs between weeks 6 and 12 of pregnancy. The peripheral conversion of testosterone into dihydrotestosterone is essential for the formation of a boy's penis, prostate and scrotum. Instead, the development of the female sexual organs in the womb is based primarily on the absence of androgens (1). Once the differentiation of the sexual organs into male or female is settled, the next thing that is differentiated is the brain, under the influence, mainly, of sex hormones on the developing brain cells. The changes (permanent) brought about in this stage have organizing effects; later, during puberty, the brain circuits that developed in the womb are activated by sex hormones. This paradigm of sexual differentiation of the brain has been well established, ever since the first paper by Phoenix et al. (2). The fetal brain is protected against the effect of circulating estrogens from the mother by the protein α-fetoprotein, which is produced by the fetus and binds strongly to estrogens but not to testosterone (3,4). However, estrogens do not only reach th...

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Section: Sex Differences In the Human Brainmentioning

confidence: 52%

Section: Sex Differences In the Human Brainmentioning

confidence: 69%

Section: Sex Differences In the Human Brainmentioning

confidence: 99%

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Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Savić

Garcı́a-Falgueras

Swaab

2010

Progress in Brain Research

121

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“…In humans, postmortem studies have also discovered several sexually dimorphic nuclei with higher cell numbers and larger volume in males within this region (Allen et al, 1989;Swaab and Fliers, 1985). Clusters of enlarged hypothalamic volume in men as well as in adolescent boys have also been detected in vivo (Goldstein et al, 2001;Lombardo et al, 2012).…”

Section: Discussionmentioning

confidence: 95%

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Hoekzema

Schagen

Kreukels

et al. 2015

Psychoneuroendocrinology

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The sexual differentiation of the brain is primarily driven by gonadal hormones during fetal development. Leading theories on the etiology of gender dysphoria (GD) involve deviations herein. To examine whether there are signs of a sex-atypical brain development in GD, we quantified regional neural gray matter (GM) volumes in 55 female-to-male and 38 male-to-female adolescents, 44 boys and 52 girls without GD and applied both univariate and multivariate analyses. In girls, more GM volume was observed in the left superior medial frontal cortex, while boys had more volume in the bilateral superior posterior hemispheres of the cerebellum and the hypothalamus. Regarding the GD groups, at whole-brain level they differed only from individuals sharing their gender identity but not from their natal sex. Accordingly, using multivariate pattern recognition analyses, the GD groups could more accurately be automatically discriminated from individuals sharing their gender identity than those sharing their natal sex based on spatially distributed GM patterns. However, region of interest analyses indicated less GM volume in the right cerebellum and more volume in the medial frontal cortex in female-to-males in comparison to girls without GD, while male-to-females had less volume in * Corresponding author. the bilateral cerebellum and hypothalamus than natal boys. Deviations from the natal sex within sexually dimorphic structures were also observed in the untreated subsamples. Our findings thus indicate that GM distribution and regional volumes in GD adolescents are largely in accordance with their respective natal sex. However, there are subtle deviations from the natal sex in sexually dimorphic structures, which can represent signs of a partial sex-atypical differentiation of the brain.

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“…Another group reported that SDN-POA lesions in male rats decreased the percentage of animals that ejaculated in a mating test, and increased latencies to mount, intromit, or ejaculate [41]. Although an exact homolog of the SDN-POA may not exist in other species, there is evidence for sexual dimorphism of the anterior hypothalamus and preoptic area in other species that have been studied [152,22,111,2], making the SDN-POA of the rat a valuable comparative model.…”

Section: Sexually Dimorphic Nucleus Of the Preoptic Area (Sdn-poa)mentioning

confidence: 99%

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

Gore¹

2008

Frontiers in Neuroendocrinology

230

122

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The ability of a species to reproduce successfully requires the careful orchestration of developmental processes during critical time points, particularly the late embryonic and early postnatal periods. This article begins with a brief presentation of the evidence for how gonadal steroid hormones exert these imprinting effects upon the morphology of sexually differentiated hypothalamic brain regions, the mechanisms underlying these effects, and their implications in adulthood. Then, I review the evidence that aberrant exposure to hormonally-active substances such as exogenous endocrine-disrupting chemicals (EDCs), may result in improper hypothalamic programming, thereby decreasing reproductive success in adulthood. The field of endocrine disruption has shed new light on the discipline of basic reproductive neuroendocrinology through studies on how early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation. Importantly, these effects may be transmitted to future generations if the germline is affected via transgenerational, epigenetic actions. By understanding the mechanisms by which natural hormones and xenobiotics affect reproductive neuroendocrine systems, we will gain a better understanding of normal developmental processes, as well as to develop the potential ability to intervene when development is disrupted.

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A Sexually Dimorphic Nucleus in the Human Brain

Cited by 482 publications

References 24 publications

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Sexual differentiation of the human brain in relation to gender identity and sexual orientation

Regional volumes and spatial volumetric distribution of gray matter in the gender dysphoric brain

Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems

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