Intralitter variation of neonatal rat lung morphology following prenatal maternal hypervitaminosis A



Prenatal exposure to excess vitamin A (160,000 USP units/day) from days 15 through 19 of gestation results in altered lung morphology, characterized by thickened septal walls and/or large areas of atelectasis and an associated high neonatal mortality. Marked variability in both morphological and physiological expression from this prenatal insult is commonly seen between litters and littermates, making analyses difficult. The present study documents morphological intralitter variation observed in vitamin A-exposed 2-day-old rats as compared to controls. Representative midhilar coronal histological sections of each lung were examined by two methods and the results compared. The first method, although less sensitive, demonstrated that five out of eight experimental rat lungs had a significantly greater percentage of tissue to airway space as compared with undisturbed controls (>43%). The second method, using several morphological criteria and a grid system to score parenchyma into classifications based on the degree of morphological variation and projected functional capability, clearly found significantly increased percentages of poor or nonfunctional lung tissue (P < 0.01) in seven out of eight pups exposed to excess vitamin A. This method of ranking the severity of adverse effects on tissue morphology allowed identification of drug-affected newborn and provided a means to quantify the alterations. Such a means for identifying affected individuals from littermates is essential to research methodologies for detecting substances which, when administered during fetal life, produce decrements of postnatal function but no gross structural abnormalities.