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Göteborgs universitets publikationer

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

Författare och institution:
Min Hu (-); Jennifer E. Richard (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Manuel Maliqueo (-); Milana Kokosar (Institutionen för neurovetenskap och fysiologi); Romina Fornes (-); Anna Benrick (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Thomas Jansson (-); Claes Ohlsson (Centre for Bone and Arthritis Research & Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition); Xiaoke Wu (-); Karolina P Skibicka (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Elisabet Stener-Victorin (-)
Publicerad i:
Proceedings of the National Academy of Sciences of the United States of America, 112 ( 46 ) s. 14348-53
ISSN:
1091-6490
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2015
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin ->
Endokrinologi och diabetes ->
Endokrinologi
Postens nummer:
228863
Posten skapad:
2015-12-21 14:34
Posten ändrad:
2016-09-02 14:08

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