Higgins Samantha L, Bhadsavle Sanat S, Gaytan Matthew N, Thomas Kara N, Golding Michael C
Department of Veterinary Physiology and Pharmacology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.
Front Cell Dev Biol. 2024 Jul 1;12:1415653. doi: 10.3389/fcell.2024.1415653. eCollection 2024.
Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry. Our analyses identified a dose threshold between 1.543 and 2.321 g/kg/day. Below this threshold, preconception paternal alcohol exposure induced changes in facial shape, including a right shift in facial features. In contrast, above this threshold, paternal exposures caused shifts in both shape and center, disrupting facial symmetry. Consistent with previous clinical studies, changes in craniofacial shape predominantly mapped to regions in the lower portion of the face, including the mandible (lower jaw) and maxilla (upper jaw). Notably, high-dose exposures also impacted the positioning of the right eye. Our studies reveal that paternal alcohol use may be an unrecognized factor contributing to the incidence and severity of alcohol-related craniofacial defects, complicating diagnostics of fetal alcohol spectrum disorders.
尽管剂量反应分析是发育毒理学的一项基本工具，但很少有研究探讨毒物剂量对后代疾病和发育异常的非遗传父系遗传的影响。在本研究中，我们使用几何形态测量分析来研究孕前父方不同水平的酒精暴露对小鼠模型后代颅面形状和对称性的影响。通过普氏方差分析，随后对几何面部关系进行典型变量分析，结果显示低剂量、中剂量和高剂量处理均诱导了颅面形状和对称性的明显变化。我们的分析确定了一个剂量阈值，介于1.543至2.321克/千克/天之间。低于该阈值时，孕前父方酒精暴露会导致面部形状发生变化，包括面部特征向右偏移。相比之下，高于该阈值时，父方暴露会导致形状和中心位置均发生偏移，从而破坏面部对称性。与先前的临床研究一致，颅面形状的变化主要集中在面部下部区域，包括下颌骨（下颌）和上颌骨（上颌）。值得注意的是，高剂量暴露还影响了右眼的位置。我们的研究表明，父方饮酒可能是导致酒精相关颅面缺陷的发生率和严重程度增加的一个未被认识到的因素，这使得胎儿酒精谱系障碍的诊断变得更加复杂。
