{"doi":"10.1038/s41593-021-00896-4","title":"Placental endocrine function shapes cerebellar development and social behavior","abstract":"Abstract Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABA A R) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO’s synthetic enzyme ( akr1c14 ) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABA A R agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.","journal":"Nature Neuroscience","year":2021,"id":148878,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":117,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9556,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":633861,"name":"Hélène Lacaille","orcid":null,"position":1,"is_corresponding":false},{"id":633123,"name":"Jiaqi J. O’Reilly","orcid":"0000-0001-5664-8189","position":2,"is_corresponding":false},{"id":633124,"name":"Jacquelyn Salzbank","orcid":"0000-0001-6352-1063","position":3,"is_corresponding":false},{"id":633125,"name":"Dana Bakalar","orcid":"0000-0001-8257-4427","position":4,"is_corresponding":false},{"id":633126,"name":"Sonia Sebaoui","orcid":"0000-0002-8920-6202","position":5,"is_corresponding":false},{"id":392412,"name":"Philippe Lière","orcid":"0000-0001-9603-0586","position":6,"is_corresponding":false},{"id":530302,"name":"Cheryl Clarkson‐Paredes","orcid":"0000-0001-7958-7913","position":7,"is_corresponding":false},{"id":417337,"name":"Toru Sasaki","orcid":"0000-0001-9301-3203","position":8,"is_corresponding":false},{"id":633127,"name":"A. G. Sathyanesan","orcid":"0000-0002-9226-7831","position":9,"is_corresponding":false},{"id":437802,"name":"Panagiotis Kratimenos","orcid":"0000-0002-7368-0436","position":10,"is_corresponding":false},{"id":62261,"name":"Jacob Ellegood","orcid":"0000-0003-1504-3321","position":11,"is_corresponding":false},{"id":62262,"name":"Jason P. Lerch","orcid":"0000-0002-4871-8578","position":12,"is_corresponding":false},{"id":271795,"name":"Yuka Imamura Kawasawa","orcid":"0000-0002-8638-6738","position":13,"is_corresponding":false},{"id":311593,"name":"Anastas Popratiloff","orcid":"0000-0002-8329-3907","position":14,"is_corresponding":false},{"id":271796,"name":"Kazue Hashimoto‐Torii","orcid":"0000-0003-4001-8259","position":15,"is_corresponding":false},{"id":271797,"name":"Vittorio Gallo","orcid":"0000-0002-2429-0845","position":16,"is_corresponding":false},{"id":392420,"name":"Michaël Schumacher","orcid":"0000-0001-6117-5371","position":17,"is_corresponding":false},{"id":633128,"name":"Anna A. Penn","orcid":"0000-0003-1539-5220","position":18,"is_corresponding":false},{"id":633122,"name":"Claire‐Marie Vacher","orcid":"0000-0002-2966-8149","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:42:46.224799Z","pmid":"34400844","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}