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Developmental Timing of the Effects of Maternal Care on Gene Expression and Epigenetic Regulation of Hormone Receptor Levels in Female Rats
Open accessAbstract
Maternal care experienced during postnatal development has enduring effects on neuroendocrine function and behavior. Previous studies in rats have illustrated the effect of maternal licking/grooming (LG) on hormone receptors and maternal behavior of adult female offspring associated with altered DNA methylation. However, the developmental timing of these effects, which provide insight into the cellular and molecular pathways through which early experience alters later behavior, had not been explored. Here, we demonstrate the developmental emergence of these outcomes and use cross-fostering to identify sensitive periods for these effects. Estrogen receptor (ER)α and ERβ mRNA levels within the medial preoptic area (MPOA) of the hypothalamus were increased by postnatal day (PN)21 in female offspring of high LG dams; LG-associated increases in oxytocin receptor mRNA levels were observed beyond the weaning period. Quantification of ERα-immunoreactivity indicated a high degree of neuroanatomical specificity of LG effects within the MPOA that were observed by PN6. Reduced DNA methylation and histone 3 lysine 9 tri-methylation and increased histone 3 lysine 4 tri-methylation at the ERα gene promoter (Esr1) were detected at PN21 in high LG female offspring. Latency to engage in maternal behavior toward donor pups was significantly shorter among high LG females. Cross-fostering revealed that maternal sensitization and MPOA ERα levels are sensitive to maternal care experienced before but not after PN10. Differential windows of plasticity were identified for ERβ and oxytocin receptor mRNA levels. These studies contribute significantly to our understanding of the molecular, neurobiological, and behavioral pathways through which variation in maternal behavior is transmitted from one generation to the next.
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Metadata
- Authors
- Peña, C. J., Neugut, Y. D., & Champagne, F. A.
- Affiliations
- Columbia University (US)
- Corresponding author
- Champagne, Frances A.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-11-01
- Volume
- 154
- Issue
- 11
- Pages
- 4340-4351
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC3800762
- OpenAlex
- W2098185693
- Cited by
- 150
- References
- 67
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 53 · 2019: 9 · 2018: 12 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 15 · 2013: 1
- FWCI
- 18.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1dp2od001674-01)
- NIH Office of the Director
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- maternal care, developmental timing, estrogen receptor alpha, estrogen receptor beta, oxytocin receptor, medial preoptic area, DNA methylation, histone methylation, sensitive period, cross-fostering, maternal behavior, gene expression, epigenetic regulation, neuroendocrine development, female rats
- MeSH terms
- Animals, Behavior, Animal, Female, Hypothalamus, Maternal Behavior, Receptors, Steroid, Sexual Maturation, Receptors, Oxytocin, Gene Expression Regulation, Developmental, DNA Methylation, Rats, Inbred LEC, Epigenesis, Genetic, Estrogen Receptor alpha, Estrogen Receptor beta, Rats
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