Prenatal Exposure to a Human Relevant Mixture of Endocrine-Disrupting Chemicals Affects Mandibular Development in Mice

Abstract

Mandible is a bony structure of neuroectodermal origin with unique characteristics that support dentition and jaw movements. In the present study, we investigated the effects of gestational exposure to a mixture of endocrine-disrupting chemicals (EDCs) on mandibular growth in mice. The mixture under study (Mixture N1) has been associated with neurodevelopmental effects in both a human cohort and animal studies. Pregnant mice were exposed throughout gestation to 0.5× (times of pregnant women’s exposure levels), 10×, 100× and 500× of Mixture N1, or the vehicle, and the mandibles of the male offspring were studied in adulthood. Micro-CT analysis showed non-monotonic effects of Mixture N1 in the distances between specific mandibular landmarks and in the crown width of M1 molar, as well as changes in the mandibular bone characteristics. The alveolar bone volume was reduced, and the trabecular separation was increased in the 500× exposed mice. Bone volume in the condyle head was increased in all treated groups. Τhe Safranin-O-stained area of mature hypertrophic chondrocytes and the width of their zones were reduced in 0.5×, 10× and 100× exposed groups. This is the first indication that prenatal exposure to an epidemiologically defined EDC mixture, associated with neurodevelopmental impacts, can also affect mandibular growth in mammals.