Pathophysiology 10 (2003) 69–75 Chronic maternal nicotine exposure during gestation and lactation and the development of the lung parenchyma in the offspring Response to nicotine withdrawal G.S. Maritz ∗ , S. Windvogel Department of Medical Biosciences, University of the Western Cape, 7535 Bellville, South Africa Received 18 August 2003; accepted 2 October 2003 Abstract The aim of this study was to investigate the effect of maternal nicotine exposure during gestation and lactation on: (1) the development of the gas exchange area of the lungs of the offspring; and (2) to determine whether these effects are reversible. Pregnant rats received daily nicotine (subcutaneously 1 mg kg -1 body weight) during gestation and lactation. Nicotine administration started 1 day after mating and lasted until weaning on postnatal day 21. The offspring were exposed to nicotine via the placenta and mother’s milk only. The lung tissue of the neonates was collected on postnatal days 14, 21, 35 and 42 and prepared for morphometry. The results obtained show that maternal nicotine exposure resulted in bigger alveolar volumes and suppressed alveolarisation in the lungs of the offspring. Flattening of the alveoli occurred as the animals aged and as a consequence the internal surface area available for gas exchange decreased; a condition that resembles panlobular emphysema. It is unlikely that these effects of maternal nicotine exposure during gestation and lactation on lung development in the offspring was due to a lower birth weight, or a reduction in the period of gestation, or a poor supply of nutrients to the offspring. The changes in the gas-exchange region of the nicotine-exposed rat pups appear to be irreversible. © 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Surface morphology; Internal surface area; Alveolar volume; Alveolar number; Alveolar flattening; Maternal nicotine exposure; Panlobular emphysema 1. Introduction It has been shown that maternal smoking in humans is as- sociated with an increased incidence in respiratory disease in the offspring [1,2]. Researchers have furthermore shown that chronic exposure of rats to whole cigarette smoke dur- ing pregnancy induced a slower pace of septal growth and thus of alveolarisation in the lungs of the offspring [3,4]. Nicotine in tobacco smoke is implicated as the causative substance. Some studies illustrated that maternal smoking results in the accumulation of nicotine [5] and cotinine [6] in the foetal tissues and an extensive epidemiological study has demonstrated a positive correlation between the concen- tration of nicotine in the maternal blood and foetal growth retardation [7]. Nicotine also accumulates in the respiratory ∗ Corresponding author. Tel.: +27-21-959-2186; fax: +27-21-959-3125. E-mail address: gmaritz@uwc.ac.za (G.S. Maritz). tract of the mouse foetus [5]. Previous studies have shown that maternal nicotine exposure during gestation and lacta- tion indeed adversely interferes with energy metabolism in the developing rat lung [8], as well as with the structural development of rat lung [9]. In some epidemiological stud- ies, a relationship is drawn between diseases of the distal airways of children of smoking parents and chronic bron- chitis and emphysema of the same individuals in adulthood [10]. Recent research using rats as animal model, also indi- cates maternal nicotine exposure during gestation and lac- tation renders the lungs of the offspring more susceptible to damage [11]. The aims of this study were therefore to determine the influence of chronic maternal nicotine expo- sure during gestation and lactation on alveolar development in the neonate after the phase of rapid alveolarisation up to postnatal day 42. This was achieved by using morphomet- ric techniques to determine the effect of maternal nicotine exposure after weaning on postnatal day 21 whereafter the animals were no longer receiving nicotine. 0928-4680/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pathophys.2003.10.001