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Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

ABSTRACT: Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 or 1.5 mg/kg/day and subsequently bred with male mice. Our results show that MNE dose-dependently increased CHDs in foetal mice. CHDs included atrial and ventricular septal defects, double outlet right ventricle, unguarded tricuspid orifice, hypoplastic left ventricle, thickened aortic and pulmonary valves, and ventricular hypertrophy. MNE also significantly reduced coronary artery size and vessel abundance in foetal hearts. Moreover, MNE resulted in higher levels of oxidative stress and altered the expression of key cardiogenic regulators in the developing heart. Nicotine exposure reduced epicardial-to-mesenchymal transition in foetal hearts. In conclusion, MNE induces CHDs and coronary artery malformation in mice. These findings provide insight into the adverse outcomes of foetuses by MNE during pregnancy.

SUBMITTER: Greco ER

PROVIDER: S-EPMC9170818 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

Greco Elizabeth R ER Engineer Anish A Saiyin Tana T Lu Xiangru X Zhang MengQi M Jones Douglas L DL Feng Qingping Q

Journal of cellular and molecular medicine 20220506 11

Maternal cigarette smoking is a risk factor for congenital heart defects (CHDs). Nicotine replacement therapies are often offered to pregnant women following failed attempts of smoking cessation. However, the impact of nicotine on embryonic heart development is not well understood. In the present study, the effects of maternal nicotine exposure (MNE) during pregnancy on foetal heart morphogenesis were studied. Adult female mice were treated with nicotine using subcutaneous osmotic pumps at 0.75 ...[more]

PMID: 35521669

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Project description:ImportanceMaternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there are no large studies analyzing outcomes associated with these factors in 1 model.ObjectiveTo investigate the association of maternal diabetes and overweight or obesity with CHDs among offspring in 1 model.Design, setting, and participantsThis nationwide, population-based register study was conducted in a birth cohort from Finland consisting of all children born between 2006 and 2016 (620 751 individuals) and their mothers. Data were analyzed from January 2022 until November 2023.ExposuresMaternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obesity (≥30), was assessed. Maternal diabetes status, classified as no diabetes, type 1 diabetes (T1D), type 2 or other diabetes, and gestational diabetes, was assessed.Main outcomes and measuresOdds ratios (ORs) of isolated CHDs in children were found. In addition, 9 anatomical CHD subgroups were studied.ResultsOf 620 751 children (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) born in Finland during the study period, 10 254 children (1.7%) had an isolated CHD. Maternal T1D was associated with increased odds of having a child with any CHD (OR, 3.77 [95% CI, 3.26-4.36]) and 6 of 9 CHD subgroups (OR range, 3.28 [95% CI, 1.55-6.95] for other septal defects to 7.39 [95% CI, 3.00-18.21] for transposition of great arteries) compared with no maternal diabetes. Maternal overweight was associated with left ventricular outflow tract obstruction (OR, 1.28 [95% CI, 1.10-1.49]) and ventricular septal defects (OR, 0.92 [95% CI, 0.86-0.98]), and obesity was associated with complex defects (OR, 2.70 [95% CI, 1.14-6.43]) and right outflow tract obstruction (OR, 1.31 [95% CI, 1.09-1.58]) compared with normal maternal BMI.Conclusions and relevanceThis study found that maternal T1D was associated with increased risk for most types of CHD in offspring, while obesity and overweight were associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. These different risk profiles of T1D and overweight and obesity may suggest distinct underlying teratogenic mechanisms.

Project description:BackgroundAlthough there is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) is linked with congenital heart defects (CHDs), few studies have examined the association in humans. We conducted a case-control study to examine the association between maternal exposure to PAHs and CHDs in offspring using data from the National Birth Defects Prevention Study (NBDPS) (1997-2011).MethodsWe obtained detailed information on maternal occupation during the month before to three months after conception. Expert raters, masked to case-control status, assessed job descriptions to assign categorical levels of exposure. Categories were quantitatively mapped to estimate cumulative exposure to PAHs, incorporating exposure intensity, frequency, work duration, and work hours. Quartiles were generated for cumulative maternal exposure to PAHs. Crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression for quartiles of PAH exposure and six CHD groupings (e.g. conotruncal) and specific subtypes (e.g. tetralogy of Fallot [ToF]). Final models were adjusted for maternal age, race/ethnicity, education, smoking, anticonvulsant use, folic acid supplementation, and study center.ResultsThere were 4,775 case and 7,734 control infants eligible for the study. The prevalence of occupational exposure to PAHs was 10.2% among both case and control mothers. In adjusted analysis, compared to mothers with no occupational PAH exposure, those in the highest quartile of exposure were more likely to have offspring in the conotruncal heart defects group (OR 1.41; 95% CI 1.00-2.00), and with ToF (OR 1.83; 95% CI 1.21-2.78).ConclusionsWomen in the highest quartile of estimated cumulative occupational PAH exposure during early pregnancy were more likely to have offspring with conotruncal heart defects, specifically ToF, compared to women with no occupational PAH exposure. Other comparisons between PAHs and other CHDs subgroups did not show any statistically precise associations.

Project description:BackgroundCongenital heart defects (CHDs) are the most common congenital malformations. The aetiology of CHDs is complex. Large cohort studies and systematic reviews and meta-analyses based on these have reported an association between higher risk of CHDs in the offspring and individual maternal metabolic disorders such as obesity, diabetes, hypertension, and preeclampsia, all conditions that can be related to insulin resistance or hyperglycaemia. However, the clinical reality is that these conditions often occur simultaneously. The aim of this review is, in consequence, both to evaluate the existing evidence on the association between maternal metabolic disorders, defined as obesity, diabetes, hypertension, preeclampsia, dyslipidaemia and CHDs in the offspring, as well as the significance of combinations, such as metabolic syndrome, as risk factors.MethodsA systematic literature search of papers published between January 1, 1990 and January 14, 2021 was conducted using PubMed and Embase. Studies were eligible if they were published in English and were case-control or cohort studies. The exposures of interest were maternal overweight or obesity, hypertension, preeclampsia, diabetes, dyslipidaemia, and/or metabolic syndrome, and the outcome of interest was CHDs in the offspring. Furthermore, the studies were included according to a quality assessment score.ResultsOf the 2,250 identified studies, 32 qualified for inclusion. All but one study investigated only the individual metabolic disorders. Some disorders (obesity, gestational diabetes, and hypertension) increased risk of CHDs marginally whereas pre-gestational diabetes and early-onset preeclampsia were strongly associated with CHDs, without consistent differences between CHD subtypes. A single study suggested a possible additive effect of maternal obesity and gestational diabetes.ConclusionsFuture studies of the role of aberrations of the glucose-insulin homeostasis in the common aetiology and mechanisms of metabolic disorders, present during pregnancy, and their association, both as single conditions and-particularly-in combination, with CHDs are needed.

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Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

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Maternal nicotine exposure induces congenital heart defects in the offspring of mice.

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