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Here, using a clinically translatable postpartum rat model, we show that synthetic oxytocin (OT) administered for postpartum hemorrhage (PPH) prophylaxis (\u2018PPH-OT\u2019), a universally administered obstetric medication, undergoes lactational transfer, confirmed by stable isotope-labeled OT and LC-MS\/MS, without altering maternal behavior or neonatal cortical OT receptor expression. In offspring, PPH-OT altered ultrasonic vocalizations during dyadic interaction and caused a male-specific reduction in social approach, without affecting other behavioral domains. Sex-stratified RNA-sequencing of the medial prefrontal cortex (mPFC) revealed pronounced transcriptional dimorphism: males showed 1,732 differentially expressed genes versus 693 in females, and a sex-by-treatment interaction contrast identified 1,229 formally sex-differentiated genes. Male mPFC downregulated genes were significantly enriched for high-confidence NDD risk genes across three independent databases \u2014 SFARI score-1 (highest confidence autism genes; OR = 4.56, p = 0.015), DBD autism (OR = 10.34, p = 7.3\u00d710\u207b\u00b9\u00b2), and SysNDD autosomal dominant (OR = 9.78, p = 8.4\u00d710\u207b\u2077) \u2014 including core regulators of cortical circuit assembly (\n                  <jats:italic>Grin2a<\/jats:italic>\n                  ,\n                  <jats:italic>Grin2b<\/jats:italic>\n                  ,\n                  <jats:italic>Reln<\/jats:italic>\n                  ,\n                  <jats:italic>Tbr1<\/jats:italic>\n                  ,\n                  <jats:italic>Mef2c<\/jats:italic>\n                  , and\n                  <jats:italic>Tcf4<\/jats:italic>\n                  ), an enrichment pattern largely restricted to males. Hypothalamic transcriptional changes were pronounced but showed no enrichment for NDD risk genes, establishing mPFC specificity. These findings identify PPH-OT as a candidate environmental modifier of male neurodevelopmental vulnerability and provide a pressing rationale for prospective investigation of neurodevelopmental outcomes in PPH-OT-exposed children.\n                <\/jats:p>","DOI":"10.64898\/2026.05.19.726042","type":"posted-content","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T14:45:12Z","timestamp":1779461112000},"source":"Crossref","is-referenced-by-count":0,"title":["Lactational transfer of synthetic oxytocin and sex-specific suppression of neurodevelopmental risk gene networks in the rat prefrontal cortex"],"prefix":"10.64898","author":[{"given":"Gokhan","family":"Serce","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tusar","family":"Giri","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsoo","family":"Son","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rencheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Laury","sequence":"additional","affiliation":[{"name":"Genome Technology Access Center (GTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"George","sequence":"additional","affiliation":[{"name":"Senior Year High School Student, Thomas Jefferson School, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine B.","family":"McCullough","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5585-4722","authenticated-orcid":false,"given":"Susan E.","family":"Maloney","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Intellectual and Developmental Disabilities Research Center, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Tycksen","sequence":"additional","affiliation":[{"name":"Genome Technology Access Center (GTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ah","family":"Goo","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Technology Access Center (MTAC), McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8460-1759","authenticated-orcid":false,"given":"Arvind","family":"Palanisamy","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052602001589000_2026.05.19.726042v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-023-00774-6"},{"key":"2026052602001589000_2026.05.19.726042v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaac.2017.03.013"},{"key":"2026052602001589000_2026.05.19.726042v1.3","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-015-0216-5"},{"key":"2026052602001589000_2026.05.19.726042v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado5609"},{"key":"2026052602001589000_2026.05.19.726042v1.5","doi-asserted-by":"crossref","unstructured":"Nagasawa M , Okabe S , Mogi K , Kikusui T . 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