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Cardiovascular disease basic research
Prenatal nicotine exposure modulates fetal growth and reduces myocardial N-cadherin expression
  1. Wang Zhenhua,
  2. Huang Ziyang
  1. Second Affiliated Hospital Of Fujian Medical University, Fujian, China


Objectives To investigate the impact of prenatal nicotine exposure on the birth weight, body shape at birth and postnatal growth of the offspring, and the expression of myocardial N-cadherin.

Background Epidemiological studies have demonstrated that low birth weight, relative increased head circumference, and decreased abdominal circumference at birth, and postnatal catch-up growth by the suboptimal intrauterine environment are associated with increased risk of death from cardiovascular disease. The influence of prenatal nicotine exposure on growth character and impact on the heart of the offspring subject is still subject to discussion. N-cadherin plays a critical role in myocardial development and function and is associated with the development of heart failure. Studies have shown a nicotine receptor mediated pathway was associated with the modulation of N-cadherin expression. In summary, we hypothesise that prenatal treatment of nicotine might alter myocardial N-cadherin expression which may predispose for impaired cardiac function in later life.

Methods Sprague–Dawley rats were infused with nicotine (12 mg/kg/day) or saline via subcutaneous osmotic mini-pumps throughout the gestation. We weighed brain, heart, lung, liver, and kidney of one randomly selected pup of each litter within 3–12 h after birth. The litter size was then reduced to eight pups to ensure equal nutrient access. Body weight was measured every 2 days after birth. Heart samples from the offspring at birth and 45 days of age were serially sliced for measuring N-cadherin by Immuno-histochemistry staining and analysed by western blot for N-cadherin expression.

Results The birth weights of prenatal nicotine exposure offspring were significantly reduced compared with control offspring (6.72±0.38 g vs 7.40±0.35; p 0.05). Brain weight-to-body weight was significantly higher, and the liver weight-to-body weight ratio was prominently lower in maternal hypoxia offspring compared with control, indicating a relative increased head circumference and decreased abdominal circumference at birth. But there were no obvious differences in mean weight ratios of heart, lung, and kidney. N-cadherin was expressed in both atrium and ventriculium, predominantly localised to adherent junctions in intercalated discs. There was a significant down-regulated protein expression of N-cadherin in prenatal nicotine exposure offspring when compare with control.

Conclusions Prenatal nicotine exposure resulted in intrauterine growth restriction with disproportion in neonatal organ size as a sign of relative increased head circumference and decreased abdominal circumference at birth of offspring who exhibited a postnatal catch-up growth. These growth characters are associated with a higher risk of cardiovascular disease. Furthermore, we demonstrate a down-regulated protein expression of N-cadherin in the myocardium from prenatal nicotine exposure offspring, which might predispose for impaired cardiac function in later life.

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