In utero benzene exposure in CD-1 mice results in increased fetal and placental size at gestational day 19, which is dependent upon intra-litter variables

Abstract

Benzene is a common environmental pollutant and carcinogen. In a previous mouse study, we found that transplacental benzene exposure increased tumor incidence in offspring, with apparent sex differences. Mouse models are widely used in developmental toxicity studies; however, they are litter-bearing and show intra-litter variability. This study sought to determine if in utero benzene exposure affects fetal and placental growth with consideration for intra-litter variables. Pregnant CD-1 mice were exposed to corn oil (vehicle control) or 200 mg/kg benzene from gestational days (GD) 8–14 and sacrificed on GD 19. Fetal-placental units were grouped by exposure, sex, and uterine horn location. Fetus and placenta growth measurements were normalized to maternal weight gain and total live litter size or the number of live fetuses in the uterine horn. In utero benzene exposure did not affect fetal survival or the distribution of fetuses between sexes or uterine horns, but did significantly increase fetal and placental size, particularly in the left uterine horn. Both male and female fetuses showed increased weight, head-rump length, head circumference, and abdominal circumference, with the left horn most affected. Placental weight and diameter also increased, with larger placentas in the left horn. Fetal heart weight increased, especially in female fetuses. Placental efficiency was not significantly altered, though benzene-exposed females had higher efficiency than males. These findings suggest that benzene induces placental toxicity, leading to altered growth, and emphasize the need to account for intra-litter variability in xenobiotic-induced developmental toxicity studies.