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Maternal oxytocin administration modulates gene expression in the brains of perinatal mice

  • Frances F. Hsieh , Ilya Korsunsky ORCID logo , Andrew J. Shih , Matthew A. Moss , Prodyot K. Chatterjee , Jaai Deshpande , Xiangying Xue , Swati Madankumar , Gopal Kumar , Burton Rochelson and Christine N. Metz ORCID logo EMAIL logo
Published/Copyright: November 1, 2021
Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 50 Issue 2

Abstract

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.

Keywords: fetal brain; in utero exposure; neuritogenesis; oxytocin; parturition
Corresponding author: Christine N. Metz, PhD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Institute of Molecular Medicine, Feinstein Institutes for Medical Research at Northwell Health, 350 Community Drive, Manhasset, NY 11030, USA; and Elmezzi Graduate School of Molecular Medicine at Northwell Health, Manhasset, NY, USA, Manhasset, NY USA, Phone: +1 516-562-3403, E-mail:
Frances F. Hsieh and Ilya Korsunsky contributed equally to this work.

Funding source: The Lax Family FoundationThe Feinstein Institutes for Medical Research

Award Identifier / Grant number: 5806

Award Identifier / Grant number: 727604

Acknowledgments

The authors would like to thank the staff of the Center for Comparative Physiology for assisting with animal care and maintenance and the staff of the Genetics Core of the Feinstein Institutes for running the microarrays.

  1. Research funding: Funding for this study was received from the Feinstein Institutes for Medical Research (CNM) and the Lax Family Foundation (BR).

  2. Author contributions: FFH, IK, BR and CNM conceived experiments and designed the study. IK (lead), AS, MAM performed gene expression studies/analyses, helped with the interpretation of gene expression studies and prepared figures showing gene expression data. FFH, JD, XX, CNM and GK performed animal experimentation, sample collection and processing, and DNA isolation. FH and PC performed RNA isolation and qPCR for Oxtr mRNA expression, sex determination, and microarray validation; both contributed to data interpretation and preparation of Tables/Figures. JD and XX performed in vitro neurogenesis assays using PC12 cells. SM prepared Table 3. FFH, SM, and CNM wrote the manuscript with input from all authors and finalized the manuscript, tables, figures, and figure legends. All authors reviewed and approved the final manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. The authors declare that they have no competing interests.

  4. Informed consent: Not applicable.

  5. Ethical approval: The Institutional Animal Care and Use Committee (IACUC) of the Feinstein Institute for Medical Research reviewed and approved the animal studies (IACUC #2015-053) prior to animal experimentation. All animal experimentation was in accordance with the National Institutes of Health guidelines for animal care. Euthanasia was performed according to The AVMA Guidelines for the Euthanasia of Animals, 2013 Edition.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2020-0525).

Received: 2020-11-06
Accepted: 2021-10-01
Published Online: 2021-11-01
Published in Print: 2022-02-23

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jpm-2020-0525
Keywords for this article
fetal brain; in utero exposure; neuritogenesis; oxytocin; parturition

Articles in the same Issue

  1. Frontmatter
  2. Corner of Academy
  3. External cephalic version in the outpatient clinic
  4. Original Articles – Obstetrics
  5. How COVID-19 pandemic is changing the practice of prenatal screening and diagnosis?
  6. Analysis of prevalence and sociodemographic conditions among women in labor with and without COVID-19 in public hospitals in Chile
  7. Influence of Covid-19 infection on fetal thymus size after recovery
  8. Second trimester fetal thymus size in association to preterm birth
  9. Heat stable carbetocin vs. oxytocin for the prevention of post-partum hemorrhage in emergency caesarean delivery: a randomized controlled trial
  10. Enhanced S100B expression in T and B lymphocytes in spontaneous preterm birth and preeclampsia
  11. The impact of parity and maternal obesity on the fetal outcomes of a non-selected Lower Saxony population
  12. Importance of frame rate for the measurement of strain and synchrony in fetuses using speckle tracking echocardiography
  13. Kidney graft function before pregnancy as a predictor of graft, maternal and fetal outcomes in pregnant renal transplant recipients
  14. Sociodemographic factors affecting perceived stress during pregnancy and the association with immune-mediator concentrations
  15. Original Articles – Neonates
  16. Smoking influence on early and late fetal growth
  17. Maternal oxytocin administration modulates gene expression in the brains of perinatal mice
  18. Original Articles – Fetus
  19. Human epididymis protein 4 and fetal lung maturity
  20. Commentary
  21. Plato unmasks hidden limits of tele-education
  22. Letter to the Editors
  23. COVID-19 delta variant and anxiety and fear in pregnant women
  24. Reply to: COVID-19 Delta variant and anxiety and fear in pregnant women
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  26. Letter Reply
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