Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain

Biology of Sex Differences

Research

Anat Biegon¹  Jana Immenschuh²  Erika Comasco²  Stefan Bernhard Thalhammer²  Inger Sundström-Poromaa³  Sylvie Dumas⁴ 

[1] Department of Radiology and Neurology, Stony Brook University School of Medicine, Stony Brook, NY, USA;Department of Women’s and Children’s Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden;Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden;Oramacell, Paris, France;

关键词: Aromatase;    Brain;    Cyp19a1;    Estrogen;    Expression;    FISH;    Gene;    mRNA;    Rat;    Sex differences;   

DOI  :  10.1186/s13293-023-00541-8

 received in 2023-05-15, accepted in 2023-08-23,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAromatase 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.MethodsCyp19a1 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.ResultsIn 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.ConclusionsFemales 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.

【 授权许可】

CC BY   
© Society for Women's Health Research and BioMed Central Ltd. 2023

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