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Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring.

Artikel i vetenskaplig tidskrift
Författare Min Hu
Jennifer E. Richard
Manuel Maliqueo
Milana Kokosar
Romina Fornes
Anna Benrick
Thomas Jansson
Claes Ohlsson
Xiaoke Wu
Karolina P Skibicka
Elisabet Stener-Victorin
Publicerad i Proceedings of the National Academy of Sciences of the United States of America
Volym 112
Nummer/häfte 46
Sidor 14348-53
ISSN 1091-6490
Publiceringsår 2015
Publicerad vid Institutionen för neurovetenskap och fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Centre for Bone and Arthritis Research
Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 14348-53
Språk en
Länkar dx.doi.org/10.1073/pnas.1507514112
Ämneskategorier Endokrinologi

Sammanfattning

During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.

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