Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain
Abstract Background Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribut...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Biology of Sex Differences |
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| Online Access: | https://doi.org/10.1186/s13293-023-00541-8 |
| _version_ | 1797578567032242176 |
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| author | Jana Immenschuh Stefan Bernhard Thalhammer Inger Sundström-Poromaa Anat Biegon Sylvie Dumas Erika Comasco |
| author_facet | Jana Immenschuh Stefan Bernhard Thalhammer Inger Sundström-Poromaa Anat Biegon Sylvie Dumas Erika Comasco |
| author_sort | Jana Immenschuh |
| collection | DOAJ |
| description | Abstract Background Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribution of cells expressing the aromatase coding gene (Cyp19a1) in limbic regions of young adult rats of both sexes, and characterized the cell types expressing this gene. Methods Cyp19a1 mRNA was mapped using fluorescent in situ hybridization (FISH). Co-expression with specific cell markers was assessed with double FISH; glutamatergic, gamma-aminobutyric acid (GABA)-ergic, glial, monoaminergic, as well as interneuron markers were tested. Automated quantification of the cells expressing the different genes was performed using CellProfiler. Sex differences in the number of cells expressing Cyp19a1 was tested non-parametrically, with the effect size indicated by the rank-biserial correlation. FDR correction for multiple testing was applied. Results In the male brain, the highest percentage of Cyp19a1 + cells was found in the medial amygdaloid nucleus and the bed nucleus of stria terminalis, followed by the medial preoptic area, the CA2/3 fields of the hippocampus, the cortical amygdaloid nucleus and the amygdalo-hippocampal area. A lower percentage was detected in the caudate putamen, the nucleus accumbens, and the ventromedial hypothalamus. In females, the distribution of Cyp19a1 + cells was similar but at a lower percentage. In most regions, the majority of Cyp19a1 + cells were GABAergic, except for in the cortical-like regions of the amygdala where most were glutamatergic. A smaller fraction of cells co-expressed Slc1a3, suggesting expression of Cyp19a1 in astrocytes; monoaminergic markers were not co-expressed. Moreover, sex differences were detected regarding the identity of Cyp19a1 + cells. Conclusions Females show overall a lower number of cells expressing Cyp19a1 in the limbic brain. In both sexes, aromatase is expressed in a region-specific manner in GABAergic and glutamatergic neurons. These findings call for investigations of the relevance of sex-specific and region-dependent expression of Cyp19a1 in the limbic brain to sex differences in behavior and mental health. |
| first_indexed | 2024-03-10T22:24:37Z |
| format | Article |
| id | doaj.art-e349a899bcbd4b0ba051d6c44bc065fa |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-03-10T22:24:37Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-e349a899bcbd4b0ba051d6c44bc065fa2023-11-19T12:11:17ZengBMCBiology of Sex Differences2042-64102023-09-0114111810.1186/s13293-023-00541-8Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brainJana Immenschuh0Stefan Bernhard Thalhammer1Inger Sundström-Poromaa2Anat Biegon3Sylvie Dumas4Erika Comasco5Department of Women’s and Children’s Health, Science for Life Laboratory, Uppsala UniversityDepartment of Women’s and Children’s Health, Science for Life Laboratory, Uppsala UniversityDepartment of Women’s and Children’s Health, Uppsala UniversityDepartment of Radiology and Neurology, Stony Brook University School of MedicineOramacellDepartment of Women’s and Children’s Health, Science for Life Laboratory, Uppsala UniversityAbstract Background Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribution of cells expressing the aromatase coding gene (Cyp19a1) in limbic regions of young adult rats of both sexes, and characterized the cell types expressing this gene. Methods Cyp19a1 mRNA was mapped using fluorescent in situ hybridization (FISH). Co-expression with specific cell markers was assessed with double FISH; glutamatergic, gamma-aminobutyric acid (GABA)-ergic, glial, monoaminergic, as well as interneuron markers were tested. Automated quantification of the cells expressing the different genes was performed using CellProfiler. Sex differences in the number of cells expressing Cyp19a1 was tested non-parametrically, with the effect size indicated by the rank-biserial correlation. FDR correction for multiple testing was applied. Results In the male brain, the highest percentage of Cyp19a1 + cells was found in the medial amygdaloid nucleus and the bed nucleus of stria terminalis, followed by the medial preoptic area, the CA2/3 fields of the hippocampus, the cortical amygdaloid nucleus and the amygdalo-hippocampal area. A lower percentage was detected in the caudate putamen, the nucleus accumbens, and the ventromedial hypothalamus. In females, the distribution of Cyp19a1 + cells was similar but at a lower percentage. In most regions, the majority of Cyp19a1 + cells were GABAergic, except for in the cortical-like regions of the amygdala where most were glutamatergic. A smaller fraction of cells co-expressed Slc1a3, suggesting expression of Cyp19a1 in astrocytes; monoaminergic markers were not co-expressed. Moreover, sex differences were detected regarding the identity of Cyp19a1 + cells. Conclusions Females show overall a lower number of cells expressing Cyp19a1 in the limbic brain. In both sexes, aromatase is expressed in a region-specific manner in GABAergic and glutamatergic neurons. These findings call for investigations of the relevance of sex-specific and region-dependent expression of Cyp19a1 in the limbic brain to sex differences in behavior and mental health.https://doi.org/10.1186/s13293-023-00541-8AromataseBrainCyp19a1EstrogenExpressionFISH |
| spellingShingle | Jana Immenschuh Stefan Bernhard Thalhammer Inger Sundström-Poromaa Anat Biegon Sylvie Dumas Erika Comasco Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain Biology of Sex Differences Aromatase Brain Cyp19a1 Estrogen Expression FISH |
| title | Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| title_full | Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| title_fullStr | Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| title_full_unstemmed | Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| title_short | Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| title_sort | sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain |
| topic | Aromatase Brain Cyp19a1 Estrogen Expression FISH |
| url | https://doi.org/10.1186/s13293-023-00541-8 |
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