Experimental models used to measure direct and indirect ethanol teratogenicity.

Abstract

The teratogenic effects of ethanol have been widely studied in a variety of experimental models. In humans, ethanol teratogenicity results from both direct and indirect effects. This paper reviews the differences between direct and indirect effects of ethanol on the developing fetus. Experimental paradigms are discussed that attempt to differentiate between direct and indirect effects. For the purpose of this review, direct effects of ethanol are caused by ethanol interacting with the fetal cell. Indirect effects of ethanol teratogenicity are defined as any perturbation of the developing fetus resulting from ethanol exposure but not caused by ethanol's interacting with the fetal cell. Indirect effects of ethanol teratogenicity include: ethanol-induced maternal undernutrition; ethanol-induced placental dysfunction and acetaldehyde teratogenicity.

Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models of PAE

“…Other mechanisms mediating alcohol’s adverse effects on neurobiological and neurobehavioral outcomes include: nutritional deprivation or deficiencies (e.g., calories, protein, zinc, folate, vitamin A); abnormalities in calcium signaling; altered prostaglandin synthesis/degradation; placental dysmorphology/dysfunction; alcohol-induced circulatory changes in placenta and (or) fetus; disrupted cell–cell interactions (cell adhesion); interference with growth factors or other cell signaling mechanisms that mediate cell proliferation, growth, differentiation, migration, and maturation; oxidative stress and damage by free radicals; disruption of neuronal development in specific cell populations (e.g., serotonergic neurons); alteration/disruption of endocrine balance and neuroendocrine function (Michaelis 1990; Randall et al 1990; West et al 1994; Guerri 1998; Shibley et al 1999; Goodlett et al 2005; Bake et al 2012; Uban et al 2013; Wieczorek et al 2015), and increased neuroinflammation (Weinberg and Gallo 1982; Randall et al 1987, 1989; Weinberg and Bezio 1987; Taylor et al 1988; Weinberg 1989, 1992, 1993; Lee et al 1990, 2000; LeBel and Bondy 1991; Halasz et al 1993; Henderson et al 1995; Kotch et al 1995; Lee and Rivier 1996; Ramanathan et al 1996; Gabriel et al 1998; Bearer 2001 a , 2001 b ; Spong et al 2001; Wilkemeyer et al 2002, 2003; Zhang et al 2005, 2012; Glavas et al 2007; Gubitosi-Klug et al 2007; Weinberg et al 2008; Sari 2009; Dong et al 2010; Bodnar and Weinberg 2013; Dou and Charness 2014; Drew et al 2015; Bodnar et al 2016). …”

Selective Vulnerability of Embryonic Cell Populations to Ethanol-Induced Apoptosis: Implications for Alcohol-Related Birth Defects and Neurodevelopmental Disorder

“…Although several cellular events, such as proliferation, migration, and differentiation, have been implicated as targets for ethanol-induced perturbation during gestation [reviewed by Michaelis and Michaelis (1994) and Shibley et al (1999)], the apoptosis of select cell populations is clearly involved in ethanol's teratogenicity. However, the basis for this selective cellular vulnerability to excessive apoptosis remains to be elucidated.…”

Efeitos da desnutrição e consumo crônico de etanol sobre o perfil histológico do pâncreas de ratos recém-natos

“…Além disso, supomos que a diminuição do peso em P3 (pós-natal precoce) foi decorrente dos efeitos indiretos do álcool relacionados à mãe, pelo fato de não ter havido diferença estática entre os pesos dos animais tratados nutridos (GE) e desnutridos (GED) entre si. Tais efeitos seriam decorrentes da interferência do etanol em todas as três fases da nutrição fetal, como evidenciado por Shibley et al (1999) 16 .…”