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Sökning: onr:"swepub:oai:gup.ub.gu.se/304100" > Prenatal androgen e...

  • Risal, S.Karolinska Institutet (författare)

Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-01-13
  • Springer Science and Business Media LLC,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/304100
  • https://gup.ub.gu.se/publication/304100URI
  • https://doi.org/10.1038/s41398-020-01183-9DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-88535URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19435URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:145772663URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Funding Agencies:Swedish Medical Research Council (SMRC) 2014-2775 2018-02435 2014-2870 2018-02119Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) 340-2013-5867SRP in Diabetes at Karolinska Institutet  Adlerbertska Foundation 2019/86Becas Chile-Conicyt 
  • CC BY 4.0Correspondence: Elisabet Stener-Victorin (elisabet.stener-victorin@ki.se)
  • 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 (F-0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F-1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F-3) in the androgenized lineage. In contrast, following the male germline, F-3 male offspring (mF(3)) 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 F-3 females in the androgenized lineage and eight genes in the obese lineage. In mF(3) 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 F-1 and F-2 offspring in the female germline did not develop anxiety-like behavior, while the F-2 male offspring (mF(2)) 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Manti, M.Karolinska Institutet (författare)
  • Lu, H. J.Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (författare)
  • Fornes, R.Karolinska Institutet (författare)
  • Larsson, Henrik,1975-Örebro universitet,Institutionen för medicinska vetenskaper,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden / School of Medical Sciences, Örebro University, Sweden(Swepub:oru)hiln (författare)
  • Benrick, Anna,1979Högskolan i Skövde,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; School of Health Sciences, University of Skövde, Skövde, Sweden,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Translationell medicin TRIM, Translational Medicine(Swepub:his)benb (författare)
  • Deng, Q. L.Karolinska Institutet (författare)
  • Cesta, C. E.Karolinska Institutet (författare)
  • Rosenqvist, M. A.School of Medical Sciences, Örebro University, Örebro, Sweden (författare)
  • Stener-Victorin, E.Karolinska Institutet (författare)
  • Karolinska InstitutetDepartment of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Translational Psychiatry: Springer Science and Business Media LLC11:12158-3188

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