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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\n                    <jats:sub>0<\/jats:sub>\n                    ) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F\n                    <jats:sub>1<\/jats:sub>\n                    ) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F\n                    <jats:sub>3<\/jats:sub>\n                    ) in the androgenized lineage. In contrast, following the male germline, F\n                    <jats:sub>3<\/jats:sub>\n                    male offspring (mF\n                    <jats:sub>3<\/jats:sub>\n                    ) 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\n                    <jats:sub>3<\/jats:sub>\n                    females in the androgenized lineage and eight genes in the obese lineage. In mF\n                    <jats:sub>3<\/jats:sub>\n                    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\n                    <jats:sub>1<\/jats:sub>\n                    and F\n                    <jats:sub>2<\/jats:sub>\n                    offspring in the female germline did not develop anxiety-like behavior, while the F\n                    <jats:sub>2<\/jats:sub>\n                    male offspring (mF\n                    <jats:sub>2<\/jats:sub>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1038\/s41398-020-01183-9","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T08:05:55Z","timestamp":1610525155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Prenatal androgen exposure causes a sexually dimorphic transgenerational increase in offspring susceptibility to anxiety disorders"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-5431","authenticated-orcid":false,"given":"Sanjiv","family":"Risal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-4780","authenticated-orcid":false,"given":"Maria","family":"Manti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-0140","authenticated-orcid":false,"given":"Haojiang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4862-3819","authenticated-orcid":false,"given":"Romina","family":"Fornes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-3297","authenticated-orcid":false,"given":"Henrik","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-6789","authenticated-orcid":false,"given":"Anna","family":"Benrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5934-7816","authenticated-orcid":false,"given":"Qiaolin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-9366","authenticated-orcid":false,"given":"Carolyn E.","family":"Cesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-2061","authenticated-orcid":false,"given":"Mina A.","family":"Rosenqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-1502","authenticated-orcid":false,"given":"Elisabet","family":"Stener-Victorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"1183_CR1","doi-asserted-by":"publisher","unstructured":"Kataoka, J. et al. 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