PMID- 34717055 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220531 IS - 1619-3997 (Electronic) IS - 0300-5577 (Linking) VI - 50 IP - 2 DP - 2022 Feb 23 TI - Maternal oxytocin administration modulates gene expression in the brains of perinatal mice. PG - 207-218 LID - 10.1515/jpm-2020-0525 [doi] AB - OBJECTIVES: Oxytocin (OXT) is widely used to facilitate labor. However, little is known about the effects of perinatal OXT exposure on the developing brain. We investigated the effects of maternal OXT administration on gene expression in perinatal mouse brains. METHODS: Pregnant C57BL/6 mice were treated with saline or OXT at term (n=6-7/group). Dams and pups were euthanized on gestational day (GD) 18.5 after delivery by C-section. Another set of dams was treated with saline or OXT (n=6-7/group) and allowed to deliver naturally; pups were euthanized on postnatal day 9 (PND9). Perinatal/neonatal brain gene expression was determined using Illumina BeadChip Arrays and real time quantitative PCR. Differential gene expression analyses were performed. In addition, the effect of OXT on neurite outgrowth was assessed using PC12 cells. RESULTS: Distinct and sex-specific gene expression patterns were identified in offspring brains following maternal OXT administration at term. The microarray data showed that female GD18.5 brains exhibited more differential changes in gene expression compared to male GD18.5 brains. Specifically, Cnot4 and Frmd4a were significantly reduced by OXT exposure in male and female GD18.5 brains, whereas Mtap1b, Srsf11, and Syn2 were significantly reduced only in female GD18.5 brains. No significant microarray differences were observed in PND9 brains. By quantitative PCR, OXT exposure reduced Oxtr expression in female and male brains on GD18.5 and PND9, respectively. PC12 cell differentiation assays revealed that OXT induced neurite outgrowth. CONCLUSIONS: Prenatal OXT exposure induces sex-specific differential regulation of several nervous system-related genes and pathways with important neural functions in perinatal brains. CI - (c) 2021 Walter de Gruyter GmbH, Berlin/Boston. FAU - Hsieh, Frances F AU - Hsieh FF AD - Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. AD - Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology Stamford Hospital, Stamford, CT, USA. FAU - Korsunsky, Ilya AU - Korsunsky I AUID- ORCID: 0000-0003-4848-3948 AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. AD - Division of Genetics, Department of Medicine at Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Shih, Andrew J AU - Shih AJ AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. FAU - Moss, Matthew A AU - Moss MA AD - Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. FAU - Chatterjee, Prodyot K AU - Chatterjee PK AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. FAU - Deshpande, Jaai AU - Deshpande J AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. AD - Providence Community Health Center, Providence, RI, USA. FAU - Xue, Xiangying AU - Xue X AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. FAU - Madankumar, Swati AU - Madankumar S AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. FAU - Kumar, Gopal AU - Kumar G AD - Elmezzi Graduate School of Molecular Medicine at Northwell Health, Manhasset, NY, USA. FAU - Rochelson, Burton AU - Rochelson B AD - Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. FAU - Metz, Christine N AU - Metz CN AUID- ORCID: 0000-0002-1013-1691 AD - Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. AD - Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, Manhasset, NY, USA. AD - Elmezzi Graduate School of Molecular Medicine at Northwell Health, Manhasset, NY, USA. LA - eng PT - Journal Article DEP - 20211101 PL - Germany TA - J Perinat Med JT - Journal of perinatal medicine JID - 0361031 RN - 50-56-6 (Oxytocin) SB - IM MH - Animals MH - Brain/drug effects/metabolism MH - Female MH - Gene Expression/drug effects MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Oxytocin/pharmacology MH - Pregnancy OTO - NOTNLM OT - fetal brain OT - in utero exposure OT - neuritogenesis OT - oxytocin OT - parturition EDAT- 2021/10/31 06:00 MHDA- 2022/04/05 06:00 CRDT- 2021/10/30 17:07 PHST- 2020/11/06 00:00 [received] PHST- 2021/10/01 00:00 [accepted] PHST- 2021/10/31 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2021/10/30 17:07 [entrez] AID - jpm-2020-0525 [pii] AID - 10.1515/jpm-2020-0525 [doi] PST - epublish SO - J Perinat Med. 2021 Nov 1;50(2):207-218. doi: 10.1515/jpm-2020-0525. Print 2022 Feb 23.