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Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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2021 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, no 1, article id 45Article in journal (Refereed) Published
Abstract [en]

If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.

Place, publisher, year, edition, pages
Springer, 2021. Vol. 11, no 1, article id 45
National Category
Obstetrics, Gynecology and Reproductive Medicine Endocrinology and Diabetes Physiology
Research subject
Translational Medicine TRIM
Identifiers
URN: urn:nbn:se:his:diva-19435DOI: 10.1038/s41398-020-01183-9ISI: 000609920200004PubMedID: 33441551Scopus ID: 2-s2.0-85099339971OAI: oai:DiVA.org:his-19435DiVA, id: diva2:1523288
Note

CC BY 4.0

Correspondence: Elisabet Stener-Victorin (elisabet.stener-victorin@ki.se)

Available from: 2021-01-28 Created: 2021-01-28 Last updated: 2024-01-17Bibliographically approved

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Benrick, Anna

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