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Lauby, S. C.

Publications and source records attributed to Lauby, S. C..

4 recordsLinked to original sources

Postnatal maternal care impacts hypothalamic Esrrg gene expression, co-expression profiles, and the DNA methylome in prenatal bisphenol-exposed rats

BackgroundEnvironmental exposures co-occurring during early life have a profound influence on neurodevelopment. Our previous work in rats suggests that postnatal maternal care modulates the effects of prenatal exposure to bisphenols, an estrogenic endocrine disrupting chemical, on offspring neurodevelopment. Elevated maternal licking/grooming and prenatal bisphenol exposure have opposing effects on estrogen receptor expression in the medial preoptic area (MPOA), which could impact expression of estrogen-responsive genes. We hypothesized that maternal licking/grooming would mitigate the effects of prenatal bisphenol exposure on estrogen receptor signaling in the developing MPOA. In addition, we hypothesized that there would be interactive effects of prenatal bisphenol exposure and maternal licking/grooming on DNA methylation nearby estrogen responsive elements. ResultsOur results suggest that maternal licking/grooming normalized prenatal bisphenol-induced upregulation of estrogen-related receptor gamma (Esrrg) expression in female pups. These mitigating impacts were also evident in co-expression gene profiles that were enriched for estrogen-responsive genes. DNA methylation analyses indicated that maternal licking/grooming levels influenced the number of differentially methylated regions for prenatal bisphenol-exposed pups. These differentially methylated regions were enriched for binding sites for transcription factors that are known to interact with estrogen receptors. Finally, supplemental "licking-like" tactile stimulation normalized the DNA methylome in prenatal bisphenol-exposed female pups, with an increase and normalization of ESRRG binding to ESRRG-responsive genes. ConclusionsThese results identify a novel biological mechanism in which maternal licking/grooming can mitigate the negative neurodevelopmental impacts of prenatal bisphenol exposure and provides a proof-of-concept for postnatal tactile stimulation as a potential intervention strategy to improve neurodevelopmental outcomes.

genomics↗

Postnatal maternal care moderates the effects of prenatal bisphenol exposure on offspring neurodevelopmental, behavioral, and transcriptomic outcomes

Bisphenols (BPs), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal BP exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal BP exposure and postnatal maternal care on neurodevelopment and behavior. Our findings suggest that the effects of prenatal BP exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal BP exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal BP exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal BP exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal BP exposure and improve health and well-being in human populations.

neuroscience↗

Early-life Temperature Exposure Affects Thyroid Hormone Receptor Signaling and Epigenetic Regulation of the Paraventricular Nucleus in Female Rat Pups

Early-life maternal care received has a profound effect on later-life behaviour in adult offspring and previous studies have suggested epigenetic mechanisms (e.g., DNA methylation) are involved. Changes in thyroid hormone receptor signaling might be related to differences in maternal care received and DNA methylation modifications. We investigated the effects of two factors in the maternal environment, temperature exposure (a proxy of maternal contact) and licking-like tactile stimulation, on these processes in week-old female rat pups. We assessed thyroid hormone receptor signaling by measuring circulating triiodothyronine and transcript abundance of thyroid hormone receptors and the thyroid hormone-responsive genes DNA methyltransferase 3a and oxytocin in the paraventricular nucleus of the hypothalamus. DNA methylation of the oxytocin promoter was assessed in relation to changes in thyroid hormone receptor binding. Repeated room temperature exposure was associated with a decrease in thyroid hormone receptor signaling measures relative to nest temperature exposure, while acute room temperature exposure was associated with an increase. Repeated room temperature exposure also increased thyroid hormone receptor binding and DNA methylation at the oxytocin promoter. These findings suggest that repeated room temperature exposure may affect DNA methylation levels as a consequence of alterations in thyroid hormone receptor signaling.

neuroscience↗

Genotype Effects and Gene x Environment Interactions on Inter-Individual Licking Received and Licking Provisioning in Female Rat Offspring

In most mammals, mothers exhibit natural variations in care that propagate between generations of female offspring. However, there is limited information on genetic variation that influences this propagation. We assessed early-life maternal care received by individual female rat offspring in relation to genetic polymorphisms linked to dopaminergic activity, maternal care provisioning, and dopaminergic activity in the maternal brain. We also conducted a systematic analysis of other genetic variants potentially related to maternal behavior in our Long-Evans rat population. We found that dopamine receptor 2 (rs107017253) variation interacted with the relationship between early-life maternal care received and dopamine levels in the nucleus accumbens which, in turn, were associated with later-life maternal care provisioning. We also discovered and validated new variants that were predicted by our systematic analysis. Our findings suggest that genetic variation influences the relationship between maternal care received and maternal care provisioning, similar to findings in human populations.

neuroscience↗