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Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice.

Wittmann W, McLennan IS - Biol Sex Differ (2013)

Bottom Line: In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males.These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards.They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.

View Article: PubMed Central - HTML - PubMed

Affiliation: Brain Health Research Centre, Department of Anatomy, University of Otago, PO Box 913, Dunedin 9054, New Zealand. ian.mclennan@otago.ac.nz.

ABSTRACT

Background: The male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin+ve) neurons in it changes after pre-pubescent development.

Methods: In mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129-147 days old).

Results: The wild-type pre-pubertal male mice had 47% more calbindin+ve neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+ males and Amh+/+ females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH.

Conclusions: The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh-/- male mice that have female-like numbers of calbindin+ve neurons at 20 days. These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards. They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.

No MeSH data available.


Related in: MedlinePlus

The CALB-SDN has pre-pubescent and adult forms that are differentially regulated. The bars are the mean number of calbindin+ve neurons ± the standard error of the mean of six mice. The Amh genotype (+/+ or -/-) is shown beneath each bar. (A) Twenty-day-old mice. *1: There was a significant effect of sex (p = 0.001), genotype (p = 0.008) and sex × genotype interaction (p = 0.022, two-way ANOVA). *2: The Amh+/+ males were significantly different to Amh-/- males (p = 0.004) and both female groups (p < 0.002 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (B) Adult mice. *3: There was a significant effect of sex (p < 0.001), genotype (p = 0.002) and sex × genotype interaction (p = 0.003, two-way ANOVA). *4: The Amh+/+ males were significantly different to all other adult groups (p = 0.002 to the Amh-/- males and p < 0.001 to both female groups, Student’s t test). *5: The adult Amh-/- males were also significantly different to both of the adult female groups (p < 0.001 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (C) The bars illustrate the mean change in cell number after 20 days. In two-way ANOVAs of age and genotype, there was a significant effect of age (p = 0.007) and genotype (p < 0.001) for the male mice and a significant effect of age (p < 0.001) for the female mice. The adult mice were significantly different to the corresponding 20-day-old mice (p = 0.037 for the Amh+/+ males, p = 0.035 for the Amh+/+ females and p = 0.017 for the Amh-/- females, Student’s t test). ♂, male; ♀, female.
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Figure 3: The CALB-SDN has pre-pubescent and adult forms that are differentially regulated. The bars are the mean number of calbindin+ve neurons ± the standard error of the mean of six mice. The Amh genotype (+/+ or -/-) is shown beneath each bar. (A) Twenty-day-old mice. *1: There was a significant effect of sex (p = 0.001), genotype (p = 0.008) and sex × genotype interaction (p = 0.022, two-way ANOVA). *2: The Amh+/+ males were significantly different to Amh-/- males (p = 0.004) and both female groups (p < 0.002 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (B) Adult mice. *3: There was a significant effect of sex (p < 0.001), genotype (p = 0.002) and sex × genotype interaction (p = 0.003, two-way ANOVA). *4: The Amh+/+ males were significantly different to all other adult groups (p = 0.002 to the Amh-/- males and p < 0.001 to both female groups, Student’s t test). *5: The adult Amh-/- males were also significantly different to both of the adult female groups (p < 0.001 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (C) The bars illustrate the mean change in cell number after 20 days. In two-way ANOVAs of age and genotype, there was a significant effect of age (p = 0.007) and genotype (p < 0.001) for the male mice and a significant effect of age (p < 0.001) for the female mice. The adult mice were significantly different to the corresponding 20-day-old mice (p = 0.037 for the Amh+/+ males, p = 0.035 for the Amh+/+ females and p = 0.017 for the Amh-/- females, Student’s t test). ♂, male; ♀, female.

Mentions: In the 20-day-old mice, there was a significant effect of sex (p = 0.001, two-way ANOVA), Amh genotype (p = 0.008) and sex × genotype interaction (p = 0.022) on the number of calbindin+ve neurons in their CALB-SDN. The wild-type 20-day-old pre-pubescent male mice had 47% more calbindin+ve neurons in their CALB-SDN than their female littermates (Figures 2 and 3A), but the size and general appearance of the neurons were not overtly dimorphic (Figures 2 and 4A). This initial sex difference was absent in the Amh-/- mice, with the Amh-/- male mice containing numbers of neurons that were no different to the female mice (Figures 2 and 3A). The difference in the number of neurons between the Amh+/+ and Amh-/- mice was highly statistically significant (p = 0.004, Student’s t test; Figure 3A). The size and appearance of the calbindin+ve neurons in the Amh-/- mice were indistinguishable from the Amh+/+ mice, for both males and females (Figures 2 and 4A).


Anti-Müllerian hormone may regulate the number of calbindin-positive neurons in the sexually dimorphic nucleus of the preoptic area of male mice.

Wittmann W, McLennan IS - Biol Sex Differ (2013)

The CALB-SDN has pre-pubescent and adult forms that are differentially regulated. The bars are the mean number of calbindin+ve neurons ± the standard error of the mean of six mice. The Amh genotype (+/+ or -/-) is shown beneath each bar. (A) Twenty-day-old mice. *1: There was a significant effect of sex (p = 0.001), genotype (p = 0.008) and sex × genotype interaction (p = 0.022, two-way ANOVA). *2: The Amh+/+ males were significantly different to Amh-/- males (p = 0.004) and both female groups (p < 0.002 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (B) Adult mice. *3: There was a significant effect of sex (p < 0.001), genotype (p = 0.002) and sex × genotype interaction (p = 0.003, two-way ANOVA). *4: The Amh+/+ males were significantly different to all other adult groups (p = 0.002 to the Amh-/- males and p < 0.001 to both female groups, Student’s t test). *5: The adult Amh-/- males were also significantly different to both of the adult female groups (p < 0.001 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (C) The bars illustrate the mean change in cell number after 20 days. In two-way ANOVAs of age and genotype, there was a significant effect of age (p = 0.007) and genotype (p < 0.001) for the male mice and a significant effect of age (p < 0.001) for the female mice. The adult mice were significantly different to the corresponding 20-day-old mice (p = 0.037 for the Amh+/+ males, p = 0.035 for the Amh+/+ females and p = 0.017 for the Amh-/- females, Student’s t test). ♂, male; ♀, female.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 3: The CALB-SDN has pre-pubescent and adult forms that are differentially regulated. The bars are the mean number of calbindin+ve neurons ± the standard error of the mean of six mice. The Amh genotype (+/+ or -/-) is shown beneath each bar. (A) Twenty-day-old mice. *1: There was a significant effect of sex (p = 0.001), genotype (p = 0.008) and sex × genotype interaction (p = 0.022, two-way ANOVA). *2: The Amh+/+ males were significantly different to Amh-/- males (p = 0.004) and both female groups (p < 0.002 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (B) Adult mice. *3: There was a significant effect of sex (p < 0.001), genotype (p = 0.002) and sex × genotype interaction (p = 0.003, two-way ANOVA). *4: The Amh+/+ males were significantly different to all other adult groups (p = 0.002 to the Amh-/- males and p < 0.001 to both female groups, Student’s t test). *5: The adult Amh-/- males were also significantly different to both of the adult female groups (p < 0.001 Amh+/+, p < 0.001 Amh-/-, Student’s t test). (C) The bars illustrate the mean change in cell number after 20 days. In two-way ANOVAs of age and genotype, there was a significant effect of age (p = 0.007) and genotype (p < 0.001) for the male mice and a significant effect of age (p < 0.001) for the female mice. The adult mice were significantly different to the corresponding 20-day-old mice (p = 0.037 for the Amh+/+ males, p = 0.035 for the Amh+/+ females and p = 0.017 for the Amh-/- females, Student’s t test). ♂, male; ♀, female.
Mentions: In the 20-day-old mice, there was a significant effect of sex (p = 0.001, two-way ANOVA), Amh genotype (p = 0.008) and sex × genotype interaction (p = 0.022) on the number of calbindin+ve neurons in their CALB-SDN. The wild-type 20-day-old pre-pubescent male mice had 47% more calbindin+ve neurons in their CALB-SDN than their female littermates (Figures 2 and 3A), but the size and general appearance of the neurons were not overtly dimorphic (Figures 2 and 4A). This initial sex difference was absent in the Amh-/- mice, with the Amh-/- male mice containing numbers of neurons that were no different to the female mice (Figures 2 and 3A). The difference in the number of neurons between the Amh+/+ and Amh-/- mice was highly statistically significant (p = 0.004, Student’s t test; Figure 3A). The size and appearance of the calbindin+ve neurons in the Amh-/- mice were indistinguishable from the Amh+/+ mice, for both males and females (Figures 2 and 4A).

Bottom Line: In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males.These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards.They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.

View Article: PubMed Central - HTML - PubMed

Affiliation: Brain Health Research Centre, Department of Anatomy, University of Otago, PO Box 913, Dunedin 9054, New Zealand. ian.mclennan@otago.ac.nz.

ABSTRACT

Background: The male brain is putatively organised early in development by testosterone, with the sexually dimorphic nucleus of the medial preoptic area (SDN) a main exemplifier of this. However, pubescent neurogenesis occurs in the rat SDN, and the immature testes secrete anti-Müllerian hormone (AMH) as well as testosterone. We have therefore re-examined the development of the murine SDN to determine whether it is influenced by AMH and/or whether the number of calbindin-positive (calbindin+ve) neurons in it changes after pre-pubescent development.

Methods: In mice, the SDN nucleus is defined by calbindin+ve neurons (CALB-SDN). The number and size of the neurons in the CALB-SDN of male and female AMH mutant (Amh-/-) mice and their wild-type littermates (Amh+/+) were studied using stereological techniques. Groups of mice were examined immediately before the onset of puberty (20 days postnatal) and at adulthood (129-147 days old).

Results: The wild-type pre-pubertal male mice had 47% more calbindin+ve neurons in the CALB-SDN than their female wild-type littermates. This sex difference was entirely absent in Amh-/- mice. In adults, the extent of sexual dimorphism almost doubled due to a net reduction in the number and size of calbindin+ve neurons in females and a net increase in neuron number in males. These changes occurred to a similar extent in the Amh-/- and Amh+/+ mice. Consequently, the number of calbindin+ve neurons in Amh-/- adult male mice was intermediate between Amh+/+ males and Amh+/+ females. The sex difference in the size of the neurons was predominantly generated by a female-specific atrophy after 20 days, independent of AMH.

Conclusions: The establishment of dimorphic cell number in the CALB-SDN of mice is biphasic, with each phase being subject to different regulation. The second phase of dimorphism is not dependent on the first phase having occurred as it was present in the Amh-/- male mice that have female-like numbers of calbindin+ve neurons at 20 days. These observations extend emerging evidence that the organisation of highly dimorphic neuronal networks changes during puberty or afterwards. They also raise the possibility that cellular events attributed to the imprinting effects of testosterone are mediated by AMH.

No MeSH data available.


Related in: MedlinePlus