Maternal oxytocin treatment at birth increases epigenetic age in male offspring

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Hauptverfasser: Joshua S. Danoff, C. Sue Carter, Juozas Gordevičius, Milda Milčiūtė, Robert T. Brooke, Jessica J. Connelly, Allison M. Perkeybile
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Veröffentlicht: Wiley 2024
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author Joshua S. Danoff
C. Sue Carter
Juozas Gordevičius
Milda Milčiūtė
Robert T. Brooke
Jessica J. Connelly
Allison M. Perkeybile
author_facet Joshua S. Danoff
C. Sue Carter
Juozas Gordevičius
Milda Milčiūtė
Robert T. Brooke
Jessica J. Connelly
Allison M. Perkeybile
Joshua S. Danoff
C. Sue Carter
Juozas Gordevičius
Milda Milčiūtė
Robert T. Brooke
Jessica J. Connelly
Allison M. Perkeybile
collection Wiley Open Access
contents Maternal oxytocin treatment at birth increases epigenetic age in male offspring Joshua S. Danoff C. Sue Carter Juozas Gordevičius Milda Milčiūtė Robert T. Brooke Jessica J. Connelly Allison M. Perkeybile Developmental Psychobiology AbstractExogenous oxytocin is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long‐lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin‐exposed animals compared to the saline‐exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and two CpG sites (two genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA‐sequencing, we also found 217 nominally differentially expressed genes (p < .05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons, six genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long‐lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the life span is supported by these outcomes. 10.1002/dev.22452 http://creativecommons.org/licenses/by-nc-nd/4.0/
doi_str_mv 10.1002/dev.22452
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license_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
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publisher Wiley
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spellingShingle Maternal oxytocin treatment at birth increases epigenetic age in male offspring
Joshua S. Danoff
C. Sue Carter
Juozas Gordevičius
Milda Milčiūtė
Robert T. Brooke
Jessica J. Connelly
Allison M. Perkeybile
Developmental Psychobiology
Maternal oxytocin treatment at birth increases epigenetic age in male offspring Joshua S. Danoff C. Sue Carter Juozas Gordevičius Milda Milčiūtė Robert T. Brooke Jessica J. Connelly Allison M. Perkeybile Developmental Psychobiology AbstractExogenous oxytocin is widely used to induce or augment labor with little understanding of the impact on offspring development. In rodent models, including the prairie vole (Microtus ochrogaster), it has been shown that oxytocin administered to mothers can affect the nervous system of the offspring with long‐lasting behavioral effects especially on sociality. Here, we examined the hypothesis that perinatal oxytocin exposure could have epigenetic and transcriptomic consequences. Prairie voles were exposed to exogenous oxytocin, through injections given to the mother just prior to birth, and were studied at the time of weaning. The outcome of this study revealed increased epigenetic age in oxytocin‐exposed animals compared to the saline‐exposed group. Oxytocin exposure led to 900 differentially methylated CpG sites (annotated to 589 genes), and two CpG sites (two genes) remained significantly different after correction for multiple comparisons. Differentially methylated CpG sites were enriched in genes known to be involved in regulation of gene expression and neurodevelopment. Using RNA‐sequencing, we also found 217 nominally differentially expressed genes (p < .05) in nucleus accumbens, a brain region involved in reward circuitry and social behavior; after corrections for multiple comparisons, six genes remained significantly differentially expressed. Finally, we found that maternal oxytocin administration led to widespread alternative splicing in the nucleus accumbens. These results indicate that oxytocin exposure during birth may have long‐lasting epigenetic consequences. A need for further investigation of how oxytocin administration impacts development and behavior throughout the life span is supported by these outcomes. 10.1002/dev.22452 http://creativecommons.org/licenses/by-nc-nd/4.0/
title Maternal oxytocin treatment at birth increases epigenetic age in male offspring
topic Developmental Psychobiology
url https://onlinelibrary.wiley.com/doi/10.1002/dev.22452