Nicotine-induced over-exposure to maternal glucocorticoid and activated glucocorticoid metabolism causes hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic alterations in fetal rats

Xu, Dan; Liang, Gang; Yan, You-e; He, W.W.; Liu, Y.S.; Chen, L.B.; Magdalou, Jacques; Wang, H.

doi:10.1016/j.toxlet.2012.01.006

Cited by 74 publications

(41 citation statements)

References 57 publications

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“…We previously confirmed that PNE induced a HPA axis-associated neuroendocrine metabolic alteration in IUGR fetal rats, which manifested as a high blood glucose level and low blood lipid levels (TG and TCH) associated with a high blood GC level [13] . After birth and the initiation of a normal diet, the level of blood glucose in IUGR offspring showed no change before chronic stress but increased significantly after chronic stress, and the level of blood TCH and TG were much higher than those in the control group before chronic stress but decreased as compared to the control after chronic stress [14] .…”

Section: Discussionsupporting

confidence: 61%

“…Our previous studies suggested that PNE induced a program of changes in the HPA axis, which was manifested as lower basal activity and enhanced stress sensitivity of the HPA axis [13,14] . Other studies showed that a high-fat diet increased the basal activity npg of the HPA axis in rats by promoting the synthesis and secretion of CRH in the hypothalamic paraventricular nucleus [35,36] .…”

Section: Discussionmentioning

confidence: 98%

“…Pregnant females were then transferred to individual cages. The rat IUGR model was induced by PNE as previously reported [13,14] . A schematic of the procedure for maternal and offspring rat treatment was shown in Figure 1.…”

Section: Methodsmentioning

confidence: 99%

“…The rat IUGR model induced by PNE was reported in our previous study [13,14] . In the present study, prenatal exposure to nicotine (2 mg·kg -1 ·d -1 ) resulted in a lower body weight compared with that of the control group (P<0.01, Figure 2A) at PW1 (the dams are highly sensitive to environmental stimulus over a fixed time course after delivery, so we weighed the neonates at PW1 but not PD1).…”

Section: Body Weight Change After Birthmentioning

confidence: 99%

“…It is known to cross the placenta and can be detected in fetal circulation, where it can affect the fetus in several ways [9][10][11][12] . Our previous studies [13] found that prenatal nicotine exposure (PNE) caused IUGR in rats; the fetuses were overexposed to maternal GC, and the development of the fetal HPA axis was inhibited. Meanwhile, the metabolic pathways for glucose and lipids in the fetal liver and gastrocnemius muscle, as well as the corresponding blood phenotypes, were affected, which could most likely be attributed to the increased fetal circulatory GC level.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Xia

Shen

et al. 2013

Acta Pharmacol Sin

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Aim: Prenatal nicotine exposure (PNE) alters the hypothalamic-pituitary-adrenocortical (HPA) axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods: Maternal Wistar rats were injected with nicotine (1.0 mg/kg, sc) twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress (UCS) during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results: UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical "catch-up" growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration (caused further increases in the serum ACTH and corticosterone levels), but also significantly changed the glucose and lipid metabolism after UCS (caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids). The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion: PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Body Weight Change After Birthmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Xia

Shen

et al. 2013

Acta Pharmacol Sin

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In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model

Suter

Abramovici²,

Griffin

et al. 2015

Birth Defects Research

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Background Fetal exposure to nicotine is not limited to maternal tobacco smoke, as electronic cigarettes have an increased prevalence of use among reproductive aged women. Animal models have shown that nicotine exposure in utero is associated with increased risk of asthma and cognitive deficits, as well as increased expression of the hippocampal glucocorticoid receptor. We hypothesized that in utero nicotine exposure is associated with epigenetic changes in the offspring lung and brain which may contribute to a memory of this exposure. Methods Sprague-Dawley rat dams received either saline or 2mg/kg of nicotine by intraperitoneal injection once daily from embryonic day 6 (e6) to e22. Pups were sacrificed on day 1 of life, and brain and lung tissues were harvested (N=3/ group). Results We found that nicotine exposed offspring have altered histone modifications in the brain. Dimethylation of lysine 9 of histone H3 is decreased (0.43-fold, p=0.03) while acetylation is increased (1.79-fold, p=0.031). Histone deacetylase (HDAC) activity is significantly decreased with nicotine exposure in brain and lung (0.11-fold, p<0.001; 0.12-fold, p<0.001, respectively). Expression of splice variant 1.7 of the glucocorticoid receptor is reduced in the nicotine exposed offspring lung (0.25-fold, p=0.038). Conclusions We conclude that nicotine exposure is associated with epigenetic alterations in the offspring and may lead to susceptibility to adult disease,. Our finding that in utero exposure to nicotine is associated with inhibition of HDAC activity in the brain of offspring is of importance as a similar inhibition has been suggested as a mechanism for the potentiation of addiction.

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Prenatal nicotine exposure induces HPA axis-hypersensitivity in offspring rats via the intrauterine programming of up-regulation of hippocampal GAD67

Lü

Dong

et al. 2017

Arch Toxicol

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The intrauterine programming of hypothalamic-pituitary-adrenal (HPA) axis hypersensitivity is associated with chronic adult diseases. Our previous studies demonstrated the HPA-axis hypersensitivity in offspring rats induced by prenatal nicotine exposure. The goal of the present study is to further investigate the intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously administered with 2.0 mg/kg day of nicotine from gestational day (GD) 9-20. A group of the pregnant rats was euthanized at GD20, and the fetal rats were extracted. The remaining rats were left to come to term, and the adult offspring were exposed to chronic stress. For adult offspring rats, prenatal nicotine exposure induced HPA-axis hypersensitivity after chronic stress, accompanied by imbalanced glutamatergic/GABAergic afferent inputs. Moreover, prenatal nicotine exposure enhanced the expression of hippocampal glutamic acid decarboxylase 67 (GAD67), accompanied by a decreased methylation ratio within nt -1019 to -689 of the GAD67 promoter, decreased expression of Dnmt1, and an increased GABA content and density of GABAergic neurons. The fetal rats exhibited changes consistent with the adult rats. Similar effects were also observed by treating the fetal hippocampal cell line H19-7 with 1-100 μM nicotine, while dihydro-β-erythroidine hydrobromide (DHβE), the specific inhibitor of α4β2nAChR, can reverse the effects caused by nicotine. These results indicate that prenatal nicotine exposure can enhance the potential excitability of the hypothalamus via the intrauterine programming of up-regulation of hippocampal GAD67. All of these results contribute to the HPA-axis hypersensitivity in adult offspring.

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Nicotine-induced over-exposure to maternal glucocorticoid and activated glucocorticoid metabolism causes hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic alterations in fetal rats

Cited by 74 publications

References 57 publications

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

In utero nicotine exposure epigenetically alters fetal chromatin structure and differentially regulates transcription of the glucocorticoid receptor in a rat model

Prenatal nicotine exposure induces HPA axis-hypersensitivity in offspring rats via the intrauterine programming of up-regulation of hippocampal GAD67

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