VCOM Research Day Program Book 2023

Medical Student Research Biomedical

25 Morphological Changes Throughout Gestation in Quaternary Ammonium Exposed Embryos

Dylan Davis; Justin Kula; Zachary Kirkpatrick; Terry C. Hrubec Corresponding author:

Edward Via College of Osteopathic Medicine-Virginia Campus

Quaternary ammonium compounds (QACs) are an exceptionally pervasive chemical used in household and commercial products. However, little is known regarding the safety of this common class of chemicals. Recent work, by our lab and others, have shown that QACs are reproductive and developmental toxicants, as well as inhibitors of mitochondrial function and cholesterol synthesis. QAC exposure in the embryo at the time of neural tube closure results in a neural tube defect (NTD). Additionally, some dosed embryos exhibited an abnormal phenotype, suggesting a malformation independent of the NTD. To further characterize these embryos, we conducted two systematic evaluations of these morphological differences. To evaluate changes in early gestation day 10 (GD10) embryos, mice received a single dose of 5 mg/kg Alkyldimethylbenzyl ammonium chloride + Didecyldimethyl ammonium chloride (ADBAC+DDAC) on GD8. Litters were collected on GD10 and embryos were standardized to those with 7 caudal somites. Fifteen selected criteria were measured on all embryos using ImageJ software;

measurements were given as a proportion of crown to rump length. Statistical differences were determined by a two-sample t test. To evaluate whether the abnormal phenotype persisted throughout gestation, a follow up experiment was conducted. In this experiment, mice were dosed with 60 mg/kg/day ADBAC+DDAC in the feed throughout breeding and gestation. Fetuses from 4 dams were evaluated on GD10, GD12, GD14, and GD16. Based on the results of the first study, it appeared that neural crest migration into the pharyngeal arches was diminished. This neural crest will form much of the face, therefore, we will evaluate morphometric changes in the head, face, and palate. It is expected that if our mice have been exposed to QACs then they will have morphological changes that will persist through out gestation. The results of the first experiment demonstrated that pharyngeal arch area was significantly smaller in dosed mice compared to controls (p = 0.003). Additionally, the area of the fore brain was significantly reduced in dosed mice (p = 0.0247). The other 13 morphometric measurements

were not significantly different. Ultimately, this study would help illustrate that phenotypic and neurological brain development can be interfered with by QAC exposure. With how pervasive QACs are in our everyday lives, our soap, laundry detergents, drying sheets; this study could help convey that we need to be more scrupulous in how we allow QACs to be used in common products.

This study was approved through IACUC protocol 21-096 and 22-009.


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