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However, the precise cellular and molecular mechanisms, are largely unclear. Animal studies can represent this complex pathophysiology at a systemic level but are expensive and ethically challenging. While simpler, in vitro models offer high-throughput opportunities. Therefore, this systematic review integrates findings of in vitro models relevant to depression in pregnancy, to generate novel hypotheses and targets for intervention.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The systematic analysis covered studies investigating glucocorticoid or cytokine challenges on placental or foetal neural progenitor cells (NPCs), with or without co-treatment with sex hormones.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of the 50 included studies, 11 used placental cells and 39 NPCs; surprisingly, only one used a combination of oestrogen and cortisol, and no study combined placental cells and NPCs. In placental cells, cortisol or cytokines decreased nutrient transporter expression and steroidogenic enzyme activity, and increased cytokine production. NPCs exhibited decreases in proliferation and differentiation, via specific molecular pathways, namely, inhibition of hedgehog signalling and activation of kynurenine pathway. In these cells, studies also highlighted epigenetic priming of stress and inflammatory pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Overall, results suggest that stress and inflammation not only detrimentally impact placental regulation of nutrients and hormones to the foetus, but also activate downstream pathways through increased inflammation in the placenta, ultimately eliciting adverse effects on foetal neurogenesis. Future research should investigate how sex hormones regulate these mechanisms, with the aim of developing targeted therapeutic approaches for depression in pregnancy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1038\/s41380-024-02866-1","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T19:51:32Z","timestamp":1733428292000},"page":"1689-1707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["From placenta to the foetus: a systematic review of in vitro models of stress- and inflammation-induced depression in pregnancy"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6187-8110","authenticated-orcid":false,"given":"Madeline","family":"Kirkpatrick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5767-4207","authenticated-orcid":false,"given":"Gargi","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Elhadidy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-3492","authenticated-orcid":false,"given":"Nicole","family":"Mariani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3485-2028","authenticated-orcid":false,"given":"Kristi","family":"Priestley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9132-5091","authenticated-orcid":false,"given":"Carmine M.","family":"Pariante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-7865","authenticated-orcid":false,"given":"Alessandra","family":"Borsini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"2866_CR1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1176\/appi.ajp.2016.16020138","volume":"174","author":"KJ O\u2019Donnell","year":"2017","unstructured":"O\u2019Donnell KJ, Meaney MJ. 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Pariante have received research funding from Johnson & Johnson for research on depression and inflammation which included cellular work (2012-2018), but this work is unrelated to that funding; moreover, less than 10% of Professor Pariante\u2019s support in the last 10 years derives from commercial collaborations, including: a strategic award from the Wellcome Trust (Neuroimmunology of Mood Disorders and Alzheimer\u2019s Disease (NIMA) Consortium, grant 104025), in partnership with Janssen, GlaxoSmithKline, Lundbeck and Pfizer; and consultation and speakers fees from Boehringer Ingelheim, Eli Lilly, Compass, Eleusis, GH Research, Lundbeck, and V\u00e4rde Partners. Professor Thuret received funding for a project on neural stem cell aging co-funded by the UK Medical Research Council and Merck Sharp & Dohme Corp. The work presented in this paper is unrelated to these awards.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interestS"}}]}}