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Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

Brock O, Keller M, Douhard Q, Bakker J - PLoS ONE (2012)

Bottom Line: Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male.By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors.These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

View Article: PubMed Central - PubMed

Affiliation: Neuroendocrinology, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. o.brock@nin.knaw.nl

ABSTRACT
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 potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

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Drawings taken from the mouse brain atlas of Paxinos and Franklin [40] showing the location of forebrain regions where Fos-ir cells were quantified (shaded areas in each panel).The medial part of the medial preoptic nucleus [MPOA (A1: Figure 30 of the mouse atlas: interaural, 3.94 mm; bregma, 0.14 mm)], the bed nucleus of the stria terminalis [BnsT (B2: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the piriform cortex [PIR (B3: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the anterior cortical amygdaloid nucleus [ACo (C4: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the medial amygdala [MeA (C5: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the posteroventral part of the medial amygdala [MePV (D6: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)], the ventrolateral part of the ventromedial hypothalamic nucleus [VMH-vl (D7: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)] and the posterodorsal part of the medial amygdale [MePD (D8: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)]. The distance of each coronal brain slice in front of (+) or behind (−) bregma is given for each panel.
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pone-0039204-g004: Drawings taken from the mouse brain atlas of Paxinos and Franklin [40] showing the location of forebrain regions where Fos-ir cells were quantified (shaded areas in each panel).The medial part of the medial preoptic nucleus [MPOA (A1: Figure 30 of the mouse atlas: interaural, 3.94 mm; bregma, 0.14 mm)], the bed nucleus of the stria terminalis [BnsT (B2: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the piriform cortex [PIR (B3: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the anterior cortical amygdaloid nucleus [ACo (C4: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the medial amygdala [MeA (C5: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the posteroventral part of the medial amygdala [MePV (D6: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)], the ventrolateral part of the ventromedial hypothalamic nucleus [VMH-vl (D7: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)] and the posterodorsal part of the medial amygdale [MePD (D8: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)]. The distance of each coronal brain slice in front of (+) or behind (−) bregma is given for each panel.

Mentions: Numbers of Fos-immunoreactive (Fos-ir) cells were counted unilaterally in one representative section of several brain nuclei (Fig. 4) implicated in the accessory and main olfactory pathways and thus in the control of sexual behavior [40]. Numbers of Fos-ir cells were quantified by an experimenter who was blind to the experimental treatment of mice. Brain sections were digitized through a video camera (Scion Corporation, CFW 1612C) attached to a microscope (Olympus MTV-3 – 20X objective), and immunoreactivity was quantified with a PC-based image analysis system using the particle-counting protocol of the NIH Image program (Version 1.37; Wayne Rasband, NIH, Bethesda, MD, USA). Digital images were made binary, and a manual threshold was used for discriminating the labelled material from the background. The number of Fos-ir cells was measured in one entire field, specifically defined for each brain region and placed in a standardized manner based on pre-defined anatomical landmarks in each single section. With a 20X objective, exclusion thresholds were set at 80 (low threshold) and 800 (high threshold) pixels to remove from the counts dark objects that were not the same size as a cell nucleus.


Female mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.

Brock O, Keller M, Douhard Q, Bakker J - PLoS ONE (2012)

Drawings taken from the mouse brain atlas of Paxinos and Franklin [40] showing the location of forebrain regions where Fos-ir cells were quantified (shaded areas in each panel).The medial part of the medial preoptic nucleus [MPOA (A1: Figure 30 of the mouse atlas: interaural, 3.94 mm; bregma, 0.14 mm)], the bed nucleus of the stria terminalis [BnsT (B2: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the piriform cortex [PIR (B3: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the anterior cortical amygdaloid nucleus [ACo (C4: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the medial amygdala [MeA (C5: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the posteroventral part of the medial amygdala [MePV (D6: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)], the ventrolateral part of the ventromedial hypothalamic nucleus [VMH-vl (D7: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)] and the posterodorsal part of the medial amygdale [MePD (D8: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)]. The distance of each coronal brain slice in front of (+) or behind (−) bregma is given for each panel.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3376129&req=5

pone-0039204-g004: Drawings taken from the mouse brain atlas of Paxinos and Franklin [40] showing the location of forebrain regions where Fos-ir cells were quantified (shaded areas in each panel).The medial part of the medial preoptic nucleus [MPOA (A1: Figure 30 of the mouse atlas: interaural, 3.94 mm; bregma, 0.14 mm)], the bed nucleus of the stria terminalis [BnsT (B2: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the piriform cortex [PIR (B3: Figure 33 of the mouse atlas: interaural, 3.58 mm; bregma, −0.22 mm)], the anterior cortical amygdaloid nucleus [ACo (C4: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the medial amygdala [MeA (C5: Figure 39 of the mouse atlas: interaural, 2.86 mm; bregma, −0.94 mm)], the posteroventral part of the medial amygdala [MePV (D6: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)], the ventrolateral part of the ventromedial hypothalamic nucleus [VMH-vl (D7: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)] and the posterodorsal part of the medial amygdale [MePD (D8: Figure 43 of the mouse atlas: interaural, 2.34 mm; bregma, −1.46 mm)]. The distance of each coronal brain slice in front of (+) or behind (−) bregma is given for each panel.
Mentions: Numbers of Fos-immunoreactive (Fos-ir) cells were counted unilaterally in one representative section of several brain nuclei (Fig. 4) implicated in the accessory and main olfactory pathways and thus in the control of sexual behavior [40]. Numbers of Fos-ir cells were quantified by an experimenter who was blind to the experimental treatment of mice. Brain sections were digitized through a video camera (Scion Corporation, CFW 1612C) attached to a microscope (Olympus MTV-3 – 20X objective), and immunoreactivity was quantified with a PC-based image analysis system using the particle-counting protocol of the NIH Image program (Version 1.37; Wayne Rasband, NIH, Bethesda, MD, USA). Digital images were made binary, and a manual threshold was used for discriminating the labelled material from the background. The number of Fos-ir cells was measured in one entire field, specifically defined for each brain region and placed in a standardized manner based on pre-defined anatomical landmarks in each single section. With a 20X objective, exclusion thresholds were set at 80 (low threshold) and 800 (high threshold) pixels to remove from the counts dark objects that were not the same size as a cell nucleus.

Bottom Line: Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male.By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors.These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

View Article: PubMed Central - PubMed

Affiliation: Neuroendocrinology, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands. o.brock@nin.knaw.nl

ABSTRACT
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 potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors.

Show MeSH
Related in: MedlinePlus