Julie Bakker

Julie Bakker
University of Liège | ulg · GIGA-Neurosciences Unit

PhD

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102
Publications
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4,276
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Publications

Publications (102)
Article
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Background Increasing numbers of adolescents seek help for gender-identity questions. Consequently, requests for medical treatments, such as puberty suppression, are growing. However, studies investigating the neurobiological substrate of gender incongruence (when birth-assigned sex and gender identity do not align) are scarce, and knowledge about...
Article
Full-text available
Purpose: Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that...
Article
Full-text available
Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds, generated by the inner ear in response to click-stimuli. A sex difference in emission strength is observed in neonates and adults, with weaker CEOAE amplitudes in males. These differences are assumed to originate from testosterone influences during prenatal male sexual differentiatio...
Article
Sexual behavior is essential for the perpetuation of a species. In female rodents, mate preference and lordosis behavior depend heavily on the integration of olfactory cues into the neuroendocrine brain, yet its underlying neural circuits are not well understood. We previously revealed that kisspeptin neurons in the anteroventral periventricular nu...
Article
Background Studies investigating the influence of perinatal hormone exposure on sexually differentiated traits would greatly benefit from biomarkers of these early hormone actions. Click-evoked otoacoustic emissions show sex differences that are thought to reflect differences in early androgen exposure. Women with complete androgen insensitivity sy...
Article
Tanycytes have been emerging as key players in the neuroendocrine control of gonadotropin-releasing hormone (GnRH) release. Rodent studies have demonstrated that the structural relationship between tanycytes and GnRH terminals in the median eminence is highly dynamic, regulated by gonadal steroids and undergoes age-related changes. Our objective wa...
Article
Sex differences have been described regarding several aspects of human brain morphology; however, the exact biological mechanisms underlying these differences remain unclear in humans. Women with the complete androgen insensitivity syndrome (CAIS), who lack androgen action in the presence of a 46,XY karyotype, offer the unique opportunity to study...
Article
We previously showed that estradiol can have both defeminizing and feminizing effects on the developing mouse brain. Pre- and early postnatal estradiol defeminized the ability to show lordosis in adulthood, whereas prepubertal estradiol feminized this ability. Furthermore, we found that estradiol upregulates progesterone receptors (PR) during devel...
Article
Odors processed by the main and accessory olfactory bulbs (MOB, AOB) are important for sexual behavior. Interestingly, both structures continue to receive new neurons during adulthood. A role for olfactory neurogenesis in sexual behavior in female mice has recently been shown and gonadal hormones such as estradiol can modulate adult neurogenesis. T...
Article
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Background: Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activit...
Article
Context: Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown. Objectives:...
Chapter
Olfaction is the sense of smell, which is mediated by specialized sensory neurons in the nasal cavity. Classically, the olfactory system is divided into two anatomically independent olfactory systems, the main olfactory system and the accessory olfactory system. Evidence from rodents indicates the presence of other spatially segregated subpopulatio...
Article
Pheromones induce sexually dimorphic neuroendocrine responses, such as LH secretion. However, the neuronal network by which pheromones are converted into signals that will initiate and modulate endocrine changes remains unclear. We asked whether two sexually dimorphic populations in the anteroventral periventricular and periventricular nuclei (AVPV...
Article
Adolescents with gender dysphoria (GD) may be treated with gonadotropin releasing hormone analogs (GnRHa) to suppress puberty and, thus, the development of (unwanted) secondary sex characteristics. Since adolescence marks an important period for the development of executive functioning (EF), we determined whether the performance on the Tower of Lon...
Article
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 3...
Article
Sex steroid hormones act on developing neural circuits regulating the hypothalamic-pituitary-gonadal axis and are involved in hormone-sensitive behaviours. These hormones act mainly via nuclear receptors, i.e. oestrogen receptor-α (ERα) and androgen receptor (AR). By using immunohistochemistry, we analysed the expression level of ERα and AR through...
Chapter
Full-text available
The present study is the first to demonstrate that sex differences in hypothalamic activation upon smelling the chemo-signal androstadienone are not acquired during sexual maturation, under the influence of gonadal hormones during puberty, but might be considered hard-wired responses, which already can be observed in prepubertal children. Moreover,...
Chapter
Olfaction is the sense of smell, which is mediated by specialized sensory neurons in the nasal cavity. Classically, the olfactory system is divided into two anatomically independent olfactory systems, the main olfactory system and the accessory olfactory system. Evidence from rodents indicates the presence of other spatially segregated subpopulatio...
Article
Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female pheno...
Article
Full-text available
The odorous steroid androstadienone, a putative male chemo-signal, was previously reported to evoke sex differences in hypothalamic activation in adult heterosexual men and women. In order to investigate whether puberty modulated this sex difference in response to androstadienone, we measured the hypothalamic responsiveness to this chemo-signal in...
Chapter
Men and women differ, not only in their anatomy but also in their behavior. Research using animal models has convincingly shown that sex differences in the brain and behavior are induced by sex hormones during a specific, hormone-sensitive period during early development. Thus, a male-typical brain is organized under the influence of testosterone,...
Article
Full-text available
Click-evoked otoacoustic emissions (CEOAEs) are echo-like sounds that are produced by the inner ear in response to click-stimuli. CEOAEs generally have a higher amplitude in women compared to men and neonates already show a similar sex difference in CEOAEs. Weaker responses in males are proposed to originate from elevated levels of testosterone dur...
Article
Full-text available
Behavioral testing methods are described for determining whether female mice can discriminate between volatile urinary pheromones of conspecifics of the same vs. opposite sex and/or in different endocrine conditions, for determining sexual partner preference, for quantifying receptive (lordosis) behavior, and for monitoring the expression of male-t...
Article
A brain circuit (the accessory olfactory system) that originates in the vomeronasal organ (VNO) and includes the accessory olfactory bulb (AOB) plus additional forebrain regions mediates many of the effects of pheromones, typically comprised of a variety of non-volatile and volatile compounds, on aspects of social behavior. A second, parallel circu...
Article
Full-text available
In rodents, kisspeptin expressing neurons are localized in two hypothalamic brain nuclei [anteroventral periventricular nucleus/periventricular nucleus continuum (AVPv/PeN) and arcuate nucleus (ARC)] and modulated by sex steroids. By using wild-type (WT) and aromatase knockout mice (ArKO, which cannot convert testosterone into estradiol) and immuno...
Chapter
Olfaction is the sense of smell, which is mediated by specialized sensory cells in the nasal cavity. Many vertebrate species, including most mammalian species, possess two distinct anatomically different olfactory systems: the main olfactory system and the accessory olfactory system. The main olfactory system is generally thought to be important in...
Article
Much evidence suggests that many, although not all, of the perinatal organizational actions of testosterone on the development of the male brain actually results from the cellular effects of estradiol formed via neural aromatization of testosterone. However, a default developmental program for the female brain has been criticized. Indeed, new resul...
Article
Context: The recent report that loss-of-function mutations in either the gene encoding neurokinin B (NKB) or its receptor (NK3R) produce gonadotropin deficiencies in humans strongly points to NKB as a key regulator of GnRH release. Objectives: We used NKB immunohistochemistry on postmortem human brain tissue to determine: 1) whether the human NK...
Article
Full-text available
The odorous steroid compound 4,16-androstadien-3-one (androstadienone), found in axillary sweat, was previously reported to evoke hypothalamic activation in heterosexual women, but not in heterosexual men. However, subjects were exposed to the pure crystalline form of androstadienone, which raised the question whether the observed hypothalamic resp...
Article
Full-text available
The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potenti...
Article
We recently reported that female aromatase knockout (ArKO) mice show deficits in sexual behaviour and a decreased population of kisspeptin-immunoreactive neurones in the rostral periventricular area of the third ventricle (RP3V), resurrecting the question of whether oestradiol actively contributes to female-typical sexual differentiation. To furthe...
Article
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Previous studies have shown that female preferences for male pheromones depend on the female's reproductive condition and the dominance status of the male. However, it is unknown which olfactory system detects the odors that result in a preference for a dominant male. Therefore, in the present study, we asked whether dominant versus subordinate mal...
Article
Full-text available
The classic view of brain and behavioral sexual differentiation holds that the neural mechanisms controlling sexual behavior in female rodents develop in the absence of ovarian sex hormone actions. However, in a previous study, female aromatase knock-out (ArKO) mice, which cannot convert testosterone to estradiol, showed deficient male-oriented par...
Article
We mapped cells immunoreactive for the phosphorylated form (p44/p42) of the mitogen-activated protein kinase (pMAPK--also known as ERK1/2) in the brain of male mice after exposure to female olfactory cues or after the display of male copulatory behaviors. Exposure to soiled bedding from estrous females or the display of coital behaviors rapidly (wi...
Article
Depression is one of the most common, costly and severe psychopathologies worldwide. Its incidence, however, differs significantly between the sexes, and depression rates in women are twice those of men. Interestingly, this sex difference emerges during adolescence. Although the adolescent period is characterised by major physical and behavioural t...
Chapter
As a graduate student, Julie Bakker became interested in the way gonadal hormones induce sex differences in the brain and behavior. Her Ph.D. research at the Erasmus University, Rotterdam, The Netherlands, focused on characterizing the role of estradiol in the sexual differentiation of partner preference in the rat. She did her first postdoctoral t...
Article
Olfactory signals play an important role so that breeding efforts are synchronized with appropriate social and environmental circumstances. In this context, the mammalian olfactory system is characterized by the existence of several olfactory subsystems that have evolved to process olfactory information. While the vomeronasal (or accessory) olfacto...
Article
Full-text available
Neurons incorporated into the adult main olfactory bulb (MOB) and accessory olfactory bulb (AOB) derive from the subventricular zone (SVZ). Despite some recent studies on the role of olfactory neurogenesis in sociosexual behaviors mediated by hormones, data on the implication of estrogens are still lacking. Taking advantage of female aromatase-knoc...
Article
The neural mechanisms controlling sexual behavior are sexually differentiated by perinatal actions of gonadal hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estrogens, that exposure to prenatal estrogens completely defeminized their potential to...
Article
A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male's testes, controls male-typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female-typical sexual differentiati...
Article
In rodent species, sexual differentiation of the brain for many reproductive processes depends largely on estradiol. This was recently confirmed again by using the alpha-fetoprotein knockout (AFP-KO) mouse model, which lacks the protective actions of alpha-fetoprotein against maternal estradiol and as a result represents a good model to determine t...
Article
Adult neurogenesis occurs most notably in the subgranular zone (SGZ) of the hippocampal dentate gyrus and in the olfactory bulb (OB) where new neurons are generated from neural progenitors cells produced in the subventricular zone (SVZ) of the forebrain. As it is well known that gonadal steroid hormones, primarily estradiol, modulate neurogenesis i...
Article
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Previous research using alpha-fetoprotein knockout and aromatase knockout (ArKO) female mice suggested that the developing hypothalamic mechanisms that later control feminine sexual behavior are protected prenatally from estradiol, whereas shortly after birth, they may be stimulated by this same sex hormone. In the present study, we found that the...
Article
Mannen en vrouwen verschillen, niet alleen in uiterlijk, maar ook in gedrag. Onderzoek met diermodellen heeft aangetoond dat geslachtsverschillen in gedrag ontstaan onder invloed van geslachtshormonen tijdens een kritieke periode in de foetale ontwikkeling waarin de hersenen het meest gevoelig zijn voor hormonale invloeden. De hersenen ontwikkelen...
Article
Pheromones have been shown to induce sexually dimorphic responses in LH secretion. Here we asked whether the sexually dimorphic population of kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) could relay sexually dimorphic information from the olfactory systems to the GnRH system. Furthermore, we analyzed the effe...
Article
Full-text available
In the field of sensory perception, one noticeable fact regarding olfactory perception is the existence of several olfactory subsystems involved in the detection and processing of olfactory information. Indeed, the vomeronasal or accessory olfactory system is usually conceived as being involved in the processing of pheromones as it is closely conne...
Article
In rodents, parts of the arginine-vasopressin (AVP) neuronal system are sexually dimorphic with males having more AVP-immunoreactive cells/fibers than females. This neuropeptide neuronal system is highly sensitive to steroids and has been proposed to play an important role in the processing of olfactory cues critical to the establishment of a socia...
Article
Full-text available
Sex differences in gonadal function are driven by either cyclical (females) or tonic (males) hypothalamic GnRH1 release and, subsequently, gonadotrophin (LH and FSH) secretion from the pituitary. This sex difference seems to depend on the perinatal actions of gonadal hormones on the hypothalamus. We used alpha-fetoprotein (AFP) knockout mice (Afp(-...
Article
We previously found that female aromatase knockout (ArKO) mice showed less investigation of socially relevant odours as well as reduced sexual behaviour. We now ask whether these behavioural deficits might be due to an inadequate processing of odours in female ArKO mice. Therefore, we exposed female ArKO mice to same- and opposite-sex urinary odour...
Article
The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differenti...
Chapter
Full-text available
In this chapter, we review recent data about the involvement of both the main and the accessory olfactory system in mate recognition and the control of sexual behavior in mice. Whereas the main olfactory system seems to play a central role in mate recognition in both male and female mice, clear sex differences emerge with regard to which olfactory...
Article
Full-text available
Estrogens are classically viewed as hormones that bind to intracellular receptors, which then act as transcription factors to modulate gene expression; however, they also affect many aspects of neuronal functioning by rapid nongenomic actions. Brain estrogen production can be regulated within minutes by changes in aromatase (estrogen synthase) acti...
Article
Previously [D.W. Wesson, M. Keller, Q. Douhard, M.J. Baum, J. Bakker, Enhanced urinary odor discrimination in female aromatase knockout mice, Horm. Behav. 49 (2006) 580-586] female aromatase knock out mice successfully learned to discriminate in a food-motivated go/no-go task between urinary volatiles from ovariectomized female mice treated with es...
Article
The neural mechanisms controlling mate recognition and heterosexual partner preference are sexually differentiated by perinatal actions of sex steroid hormones. We previously showed that the most important action of oestrogen during prenatal development is to defeminise and, to some extent, masculinise brain and behaviour in mice. Female mice defic...
Article
Full-text available
Alpha-fetoprotein (AFP) is a well-known diagnostic biomarker used in medicine to detect fetal developmental anomalies such as neural tube defects or Down's syndrome, or to follow up the development of tumors such as hepatocellular carcinomas. However, and despite the fact that the protein was discovered almost half a century ago, little was known a...
Article
We have previously shown that male mice carrying a targeted mutation in the Cyp19 gene which encodes the aromatase enzyme (aromatase knockout or ArKO), showed a reduced interest to investigate volatile odors from conspecifics in a Y-maze. We asked here whether the incentive value of reproductively relevant odors is reduced in ArKO males by comparin...
Article
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Recent studies point to an important role for the main olfactory epithelium (MOE) in regulating sexual behavior in male mice. We asked whether sexual experience could compensate for the disruptive effects of lesioning the MOE on sexual behavior in male mice. Male mice, which were either sexually naive or experienced, received an intranasal irrigati...
Article
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We studied the contribution of the main olfactory system to mate recognition and sexual behavior in female mice. Female mice received an intranasal irrigation of either a zinc sulfate (ZnSO4) solution to destroy the main olfactory epithelium (MOE) or saline (SAL) to serve as control. ZnSO4-treated female mice were no longer able to reliably disting...
Article
We asked whether odor discrimination abilities are sexually dimorphic in mice and, if so, whether the perinatal actions of estradiol contribute to these sex differences. The ability to discriminate different types of urinary odors was compared in male and female wild-type (WT) subjects and in mice with a homozygous-null mutation of the estrogen syn...
Article
Full-text available
It has been shown previously that female mice homozygous for an alpha-fetoprotein (AFP) null allele are sterile as a result of anovulation, probably due to a defect in the hypothalamic-pituitary axis. Here we show that these female mice exhibit specific anomalies in the expression of numerous genes in the pituitary, including genes involved in the...
Article
Full-text available
Two clearly opposing views exist on the function of alpha-fetoprotein (AFP), a fetal plasma protein that binds estrogens with high affinity, in the sexual differentiation of the rodent brain. AFP has been proposed to either prevent the entry of estrogens or to actively transport estrogens into the developing female brain. The availability of Afp mu...
Article
The role of the vomeronasal organ (VNO) in mediating neuroendocrine responses in female mice is well known; however, whether the VNO is equally important for sex discrimination is more controversial as evidence exists for a role of the main olfactory system in mate recognition. Therefore, we studied the effect of VNO removal (VNOx) on the ability o...
Article
We previously found that both male and female aromatase knockout (ArKO) mice, which cannot synthesize estrogens due to a targeted mutation of the aromatase gene, showed less investigation of volatile body odors from anesthetized conspecifics of both sexes in Y-maze tests. We now ask whether ArKO mice are in fact capable of discriminating between an...
Article
It is well known that estradiol derived from neural aromatization of testosterone plays a crucial role in the development of the male brain and the display of sexual behaviors in adulthood. It was recently found that male aromatase knockout mice (ArKO) deficient in estradiol due to a mutation in the aromatase gene have general deficits in coital be...
Article
We recently found that female aromatase knockout (ArKO) mice that are deficient in oestradiol due to a targeted mutation in the aromatase gene show deficits in sexual behaviour that cannot be corrected by adult treatment with oestrogens. We determined here whether these impairments are associated with changes in general levels of activity, anxiety...
Article
We previously found that male aromatase knockout (ArKO) mice that carry a targeted mutation in exons 1 and 2 of the CYP19 gene and as a result cannot aromatize androgen to estrogen show impaired sexual behavior in adulthood. To determine whether this impairment was due to a lack of activation of sexual behavior by estradiol, we studied here male co...
Article
The present study was carried out to determine whether aromatase knockout (ArKO) mice are completely devoid of aromatase activity in their brain and gonads and to compare aromatase activity in wild-type and ArKO mice, as well as in heterozygous (HET) mice of both sexes that were previously shown to display a variety of reproductive behaviours at le...
Article
The classic view of sexual differentiation is that the male brain develops under the influence of testicular secretions, whereas the female brain develops in the absence of any hormonal stimulation. However, several studies have suggested a possible role of estradiol in female neural development, although they did not provide unequivocal evidence t...