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FASEB J. 2018 Aug;32(8):4158-4171. doi: 10.1096/fj.201701263RR. Epub 2018 Mar 22.

Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.

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Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology, Qiqihar Medical University, Qiqihar, China.
Department of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden.
West Division, Endocrinology and Metabolism Laboratory, School of Medicine, University of Chile, Santiago, Chile.
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
School of Health and Education, University of Skövde, Skövde, Sweden.


Maternal polycystic ovary syndrome (PCOS), a condition associated with hyperandrogenism, is suggested to increase anxiety-like behavior in the offspring. Because PCOS is closely linked to obesity, we investigated the impact of an adverse hormonal or metabolic maternal environment and offspring obesity on anxiety in the offspring. The obese PCOS phenotype was induced by chronic high-fat-high-sucrose (HFHS) consumption together with prenatal dihydrotestosterone exposure in mouse dams. Anxiety-like behavior was assessed in adult offspring with the elevated-plus maze and open-field tests. The influence of maternal androgens and maternal and offspring diet on genes implicated in anxiety were analyzed in the amygdala and hypothalamus with real-time PCR ( n = 47). Independent of diet, female offspring exposed to maternal androgens were more anxious and displayed up-regulation of adrenoceptor α 1B in the amygdala and up-regulation of hypothalamic corticotropin-releasing hormone ( Crh). By contrast, male offspring exposed to a HFHS maternal diet had increased anxiety-like behavior and showed up-regulation of epigenetic markers in the amygdala and up-regulation of hypothalamic Crh. Overall, there were substantial sex differences in gene expression in the brain. These findings provide novel insight into how maternal androgens and obesity exert sex-specific effects on behavior and gene expression in the offspring of a PCOS mouse model.-Manti, M., Fornes, R., Qi, X., Folmerz, E., Lindén Hirschberg, A., de Castro Barbosa, T., Maliqueo, M., Benrick, A., Stener-Victorin, E. Maternal androgen excess and obesity induce sexually dimorphic anxiety-like behavior in the offspring.


amygdala; dihydrotestosterone; high-fat–high-sucrose; polycystic ovary syndrome


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