Sexual Differentiation and Sex Differences in Neural Development

2018 ◽  
pp. 69-110 ◽  
Author(s):  
Alexandra Turano ◽  
Brittany F. Osborne ◽  
Jaclyn M. Schwarz
Keyword(s):  
Sex Differences ◽  
Neural Development ◽  
Sexual Differentiation

scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

scholarly journals Sex Differences in the Epigenome: A Cause or Consequence of Sexual Differentiation of the Brain?

Genes ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 432 ◽  
Author(s):  
Bruno Gegenhuber ◽  
Jessica Tollkuhn
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Hormone Receptors ◽  
Neurological Diseases ◽  
Activity Patterns ◽  
Regulatory Elements ◽  
The Body ◽  
Epigenetic Mechanism ◽  
The Brain

Females and males display differences in neural activity patterns, behavioral responses, and incidence of psychiatric and neurological diseases. Sex differences in the brain appear throughout the animal kingdom and are largely a consequence of the physiological requirements necessary for the distinct roles of the two sexes in reproduction. As with the rest of the body, gonadal steroid hormones act to specify and regulate many of these differences. It is thought that transient hormonal signaling during brain development gives rise to persistent sex differences in gene expression via an epigenetic mechanism, leading to divergent neurodevelopmental trajectories that may underlie sex differences in disease susceptibility. However, few genes with a persistent sex difference in expression have been identified, and only a handful of studies have employed genome-wide approaches to assess sex differences in epigenomic modifications. To date, there are no confirmed examples of gene regulatory elements that direct sex differences in gene expression in the brain. Here, we review foundational studies in this field, describe transcriptional mechanisms that could act downstream of hormone receptors in the brain, and suggest future approaches for identification and validation of sex-typical gene programs. We propose that sexual differentiation of the brain involves self-perpetuating transcriptional states that canalize sex-specific development.

scholarly journals Evidence of Altered Brain Sexual Differentiation in Mice Exposed Perinatally to Low, Environmentally Relevant Levels of Bisphenol A

Endocrinology ◽  
2006 ◽  
Vol 147 (8) ◽  
pp. 3681-3691 ◽  
Author(s):  
Beverly S. Rubin ◽  
Jenny R. Lenkowski ◽  
Cheryl M. Schaeberle ◽  
Laura N. Vandenberg ◽  
Paul M. Ronsheim ◽  
...  
Keyword(s):  
Sex Differences ◽  
Bisphenol A ◽  
Brain Development ◽  
Sexual Differentiation ◽  
Female Offspring ◽  
Sexually Dimorphic ◽  
Critical Periods ◽  
Neuron Number ◽  
Brain Sexual Differentiation ◽  
Estrogenic Chemical

Humans are routinely exposed to bisphenol A (BPA), an estrogenic chemical present in food and beverage containers, dental composites, and many products in the home and workplace. BPA binds both classical nuclear estrogen receptors and facilitates membrane-initiated estrogenic effects. Here we explore the ability of environmentally relevant exposure to BPA to affect anatomical and functional measures of brain development and sexual differentiation. Anatomical evidence of alterations in brain sexual differentiation were examined in male and female offspring born to mouse dams exposed to 0, 25, or 250 ng BPA/kg body weight per day from the evening of d 8 of gestation through d 16 of lactation. These studies examined the sexually dimorphic population of tyrosine hydroxylase (TH) neurons in the rostral periventricular preoptic area, an important brain region for estrous cyclicity and estrogen-positive feedback. The significant sex differences in TH neuron number observed in control offspring were diminished or obliterated in offspring exposed to BPA primarily because of a decline in TH neuron number in BPA-exposed females. As a functional endpoint of BPA action on brain sexual differentiation, we examined the effects of perinatal BPA exposure on sexually dimorphic behaviors in the open field. Data from these studies revealed significant sex differences in the vehicle-exposed offspring that were not observed in the BPA-exposed offspring. These data indicate that BPA may be capable of altering important events during critical periods of brain development.

Gonadal hormone effects on entrained and free-running circadian activity rhythms in the developing diurnal rodent Octodon degus

2007 ◽  
Vol 292 (1) ◽  
pp. R586-R597 ◽  
Author(s):  
Daniel L. Hummer ◽  
Tammy J. Jechura ◽  
Megan M. Mahoney ◽  
Theresa M. Lee
Keyword(s):  
Sex Differences ◽  
Sex Difference ◽  
Sexual Differentiation ◽  
Gonadal Hormones ◽  
Circadian System ◽  
System Structure ◽  
Octodon Degus ◽  
Activity Rhythms ◽  
Free Running ◽  
The Impact

The slowly maturing, long-lived rodent Octodon degus (degu) provides a unique opportunity to examine the development of the circadian system during adolescence. These studies characterize entrained and free-running activity rhythms in gonadally intact and prepubertally gonadectomized male and female degus across the first year of life to clarify the impact of sex and gonadal hormones on the circadian system during adolescence. Gonadally intact degus exhibited a delay in the phase angle of activity onset (Ψon) during puberty, which reversed as animals became reproductively competent. Gonadectomy before puberty prevented this phase delay. However, the effect of gonadal hormones during puberty on Ψon does not result from changes in the period of the underlying circadian pacemaker. A sex difference in Ψon and free-running period (τ) emerged several months after puberty; these developmental changes are not likely to be related, since the sex difference in Ψon emerged before the sex difference in τ. Changes in the levels of circulating hormones cannot explain the emergence of these sex differences, since there is a rather lengthy delay between the age at which degus reach sexual maturity and the age at which Ψon and τ become sexually dimorphic. However, postnatal exposure to gonadal hormones is required for sexual differentiation of Ψon and τ, since these sex differences were absent in prepubertally gonadectomized degus. These data suggest that gonadal hormones modulate the circadian system during adolescent development and provide a new model for postpubertal sexual differentiation of a central nervous system structure.

The 13th J. A. F. Stevenson Memorial Lecture Sexual differentiation of the brain: possible mechanisms and implications

1985 ◽  
Vol 63 (6) ◽  
pp. 577-594 ◽  
Author(s):  
Roger A. Gorski
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Gonadal Hormones ◽  
Model Systems ◽  
Memorial Lecture ◽  
Actual Structure ◽  
The Central Nervous System ◽  
The Brain

The mammalian brain appears to be inherently feminine and the action of testicular hormones during development is necessary for the differentiation of the masculine brain both in terms of functional potential and actual structure. Experimental evidence for this statement is reviewed in this discussion. Recent discoveries of marked structural sex differences in the central nervous system, such as the sexually dimorphic nucleus of the preoptic area in the rat, offer model systems to investigate potential mechanisms by which gonadal hormones permanently modify neuronal differentiation. Although effects of these steroids on neurogenesis and neuronal migration and specification have not been conclusively eliminated, it is currently believed, but not proven, that the principle mechanism of steroid action is to maintain neuronal survival during a period of neuronal death. The structural models of the sexual differentiation of the central nervous system also provide the opportunity to identify sex differences in neurochemical distribution. Two examples in the rat brain are presented: the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus and of tyrosine hydroxylase-immunoreactive fibers and cells in the anteroventral periventricular nucleus. It is likely that sexual dimorphisms will be found to be characteristic of many neural and neurochemical systems. The final section of this review raises the possibility that the brain of the adult may, in response to steroid action, be morphologically plastic, and considers briefly the likelihood that the brain of the human species is also influenced during development by the hormonal environment.

scholarly journals Analysis of female song provides insight into the evolution of sex differences in a widely studied songbird

2020 ◽  
Author(s):  
Matthew R. Wilkins ◽  
Karan J. Odom ◽  
Lauryn Benedict ◽  
Rebecca J. Safran
Keyword(s):  
Sex Differences ◽  
Sexual Differentiation ◽  
Animal Communication ◽  
Phenotypic Traits ◽  
Phenotypic Differences ◽  
Female Song ◽  
Fitness Consequences ◽  
Song Production ◽  
Foundational Research ◽  
Patterns And Processes

ABSTRACTUnderstanding the patterns and processes related to sexual dimorphism and sex differences in diverse animal taxa is a foundational research topic in ecology and evolution. Within the realm of animal communication, studies have traditionally focused on male signals, assuming that female choice and male-male competition have promoted sex differences via elaboration of male traits, but selection on females also has the potential to drive sexual differentiation in signals. Here, we describe female song in barn swallows (Hirundo rustica erythrogaster) for the first time, report rates of female song production, and couple song data with plumage data to explore the relative degree to which sex differences in phenotypic traits are consistent with contemporary selection on males versus females. During previous intensive study of male song over two years, we opportunistically recorded songs for 15 females, with matched phenotypic and fitness data. We randomly selected 15 high-quality samples from our larger male dataset to test whether sex differences in song and plumage are more strongly associated with fledgling success for females or genetic paternity for males. Analyses included 35 potential sexual signals including 22 song parameters and 13 plumage traits. Outcomes indicate that: female songs were used in multiple contexts, restricted primarily to the beginning of the breeding season; song traits showed greater sexual differentiation than visual plumage traits; and trait correlations with reproductive success in females, rather than males, predicted sex-based differences in song and plumage. These results are consistent with phylogenetic studies showing that sex-based phenotypic differences are driven by changes in females, highlighting the potential role of female trait evolution in explaining patterns of sexual differentiation. To achieve a better understanding of sex differences and dimorphism, we require comprehensive studies that measure the same traits in males and females and their fitness consequences.

scholarly journals A frog with three sex chromosomes that co-mingle together in nature: Xenopus tropicalis has a degenerate W and a Y that evolved from a Z chromosome

PLoS Genetics ◽  
2020 ◽  
Vol 16 (11) ◽  
pp. e1009121
Author(s):  
Benjamin L. S. Furman ◽  
Caroline M. S. Cauret ◽  
Martin Knytl ◽  
Xue-Ying Song ◽  
Tharindu Premachandra ◽  
...  
Keyword(s):  
Sex Differences ◽  
Y Chromosome ◽  
Sex Chromosomes ◽  
Sexual Differentiation ◽  
Sex Chromosome ◽  
Xenopus Tropicalis ◽  
Z Chromosome ◽  
W Chromosome ◽  
Recombination Suppression ◽  
Determining Factor

In many species, sexual differentiation is a vital prelude to reproduction, and disruption of this process can have severe fitness effects, including sterility. It is thus interesting that genetic systems governing sexual differentiation vary among—and even within—species. To understand these systems more, we investigated a rare example of a frog with three sex chromosomes: the Western clawed frog, Xenopus tropicalis. We demonstrate that natural populations from the western and eastern edges of Ghana have a young Y chromosome, and that a male-determining factor on this Y chromosome is in a very similar genomic location as a previously known female-determining factor on the W chromosome. Nucleotide polymorphism of expressed transcripts suggests genetic degeneration on the W chromosome, emergence of a new Y chromosome from an ancestral Z chromosome, and natural co-mingling of the W, Z, and Y chromosomes in the same population. Compared to the rest of the genome, a small sex-associated portion of the sex chromosomes has a 50-fold enrichment of transcripts with male-biased expression during early gonadal differentiation. Additionally, X. tropicalis has sex-differences in the rates and genomic locations of recombination events during gametogenesis that are similar to at least two other Xenopus species, which suggests that sex differences in recombination are genus-wide. These findings are consistent with theoretical expectations associated with recombination suppression on sex chromosomes, demonstrate that several characteristics of old and established sex chromosomes (e.g., nucleotide divergence, sex biased expression) can arise well before sex chromosomes become cytogenetically distinguished, and show how these characteristics can have lingering consequences that are carried forward through sex chromosome turnovers.

scholarly journals Epigenetic Control of Sexual Differentiation of the Bed Nucleus of the Stria Terminalis

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4241-4247 ◽  
Author(s):  
Elaine K. Murray ◽  
Annie Hien ◽  
Geert J. de Vries ◽  
Nancy G. Forger
Keyword(s):  
Cell Death ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Cell Number ◽  
Histone Deacetylation ◽  
Postnatal Life ◽  
Sexually Dimorphic ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Deacetylase Inhibitor

Abstract The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is larger in volume and contains more cells in male than female mice. These sex differences depend on testosterone and arise from a higher rate of cell death during early postnatal life in females. There is a delay of several days between the testosterone surge at birth and sexually dimorphic cell death in the BNSTp, suggesting that epigenetic mechanisms may be involved. We tested the hypothesis that chromatin remodeling plays a role in sexual differentiation of the BNSTp by manipulating the balance between histone acetylation and deacetylation using a histone deacetylase inhibitor. In the first experiment, a single injection of valproic acid (VPA) on the day of birth increased acetylation of histone H3 in the brain 24 h later. Next, males, females, and females treated neonatally with testosterone were administered VPA or saline on postnatal d 1 and 2 and killed at 21 d of age. VPA treatment did not influence volume or cell number of the BNSTp in control females but significantly reduced both parameters in males and testosterone-treated females. As a result, the sex differences were eliminated. VPA did not affect volume or cell number in the suprachiasmatic nucleus or the anterodorsal nucleus of the thalamus, which also did not differ between males and females. These findings suggest that a disruption in histone deacetylation may lead to long-term alterations in gene expression that block the masculinizing actions of testosterone in the BNSTp.

Sex differences in the serum concentrations of testosterone in mice and hamsters during their critical periods of neural sexual differentiation

1984 ◽  
Vol 100 (1) ◽  
pp. 7-11 ◽  
Author(s):  
S. F. Pang ◽  
F. Tang
Keyword(s):  
Sex Differences ◽  
Sexual Differentiation ◽  
Critical Period ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Critical Periods ◽  
Minimum Concentration ◽  
Male And Female ◽  
Dose Dependent ◽  
Circulating Levels

ABSTRACT Male and female mice and hamsters were decapitated 1–5 days after birth and serum concentrations of testosterone determined by radioimmunoassay. In the two species studied, serum levels of testosterone in male pups were significantly (P <0·05) higher than those obtained in female neonates. This lends support to the hypothesis that circulating levels of testosterone play an important role in the process of neural sexual differentiation in rodents. Moreover, the sex differences in serum concentrations of testosterone in neonatal rodents together with the detectable levels of testosterone in female neonates may suggest that androgenization is a dose-dependent phenomenon. Alternatively, they may indicate that a minimum concentration of the steroid must be present for androgenization to occur during the critical period of neural sexual differentiation and that this 'threshold' is exceeded in male but not in female rodents. J. Endocr. (1984) 100, 7–11

Inflammatory Signals and Sexual Differentiation of the Brain

2019 ◽  
Author(s):  
Margaret M. McCarthy
Keyword(s):  
Sex Differences ◽  
Sexual Differentiation ◽  
Developmental Disorders ◽  
Additional Risk Factor ◽  
Gonadal Steroid ◽  
Maternal Immune System ◽  
Prenatal Inflammation ◽  
And Behavior ◽  
Hormonal Milieu ◽  
The Brain

Sex differences in the brain are established by the differential gonadal steroid hormonal milieu experienced by developing male and female fetuses and newborns. Androgen production by the testis starts in males prior to birth resulting in a brief developmental window during which the brain is exposed to high levels of steroid. Androgens and aromatized estrogens program the developing brain toward masculinized physiology and behavior that is then manifest in adulthood. In rodents, the perinatal programming of sex-specific adult mating behavior provides a model system for exploring the mechanistic origins of brain sex differences. Microglia are resident in the brain and provide innate immunity. Previously considered restricted to response to injury, these cells are now thought to be major contributors to the sculpting of developing neural circuits. This role extends to being an important component of the sexual differentiation process and has opened the door for exploration into myriad other aspects of neuroimmunity and inflammation as possible determinants of sex differences. In humans, males are at greater risk for more frequent and/or more severe neuropsychiatric and neurological disorders of development, many of which include prenatal inflammation as an additional risk factor. Emerging clinical and preclinical evidence suggests male brains experience a higher inflammatory tone early in development, and this may have its origins in the maternal immune system. Collectively, these disparate observations coalesce into a coherent picture in which brain development diverges in males versus females due to a combination of gonadal steroid action and neuroinflammation, and the latter increases the risk to males of developmental disorders.

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