Preprint Article Version 1 This version is not peer-reviewed

Prenatal Exposure to a Human Relevant Mixture of EDCs Affects Mandibular Development in Mice

Version 1 : Received: 10 September 2024 / Approved: 11 September 2024 / Online: 11 September 2024 (17:08:57 CEST)

How to cite: Rinotas, V.; Stamatakis, A.; Stergiopoulos, A.; Bornehag, C.-G.; Rüegg, J.; Armaka, M.; Kitraki, E. Prenatal Exposure to a Human Relevant Mixture of EDCs Affects Mandibular Development in Mice. Preprints 2024, 2024090870. https://doi.org/10.20944/preprints202409.0870.v1 Rinotas, V.; Stamatakis, A.; Stergiopoulos, A.; Bornehag, C.-G.; Rüegg, J.; Armaka, M.; Kitraki, E. Prenatal Exposure to a Human Relevant Mixture of EDCs Affects Mandibular Development in Mice. Preprints 2024, 2024090870. https://doi.org/10.20944/preprints202409.0870.v1

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 0.5x (times of pregnant women exposure levels), 10x, 100x and 500x 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 500X exposed mice. Bone volume in the condyle head was increased in all treated groups. The Alcian blue stained area of pre-hypertrophic chondrocytes in condyle’s head was increased in 0.5x, 10x and 100x groups, while the Safranin-O-stained area of mature hypertrophic chondrocytes was respectively reduced. 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.

Keywords

EDCs; mandible; mice; micro-CT

Subject

Biology and Life Sciences, Endocrinology and Metabolism

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