Dynamic and Persistent Effects of Ethanol Exposure on Development: An In Vivo Analysis During and After Embryonic Ethanol Exposure in Caenorhabditis elegans

Abstract

Background Defects caused by ethanol (EtOH) exposure during development can be different depending on the time of observation. To investigate this temporal component of developmental delay, we use the fast‐developing nematode model Caenorhabditis elegans. We first defined the longitudinal effects of EtOH on development using age‐appropriate markers and then closely followed embryonic development before, during, and after EtOH exposure. Methods C. elegans embryos were bathed in 0 to 20% EtOH (w/w in ddH2O) for 8 hours or were left untreated during embryonic development. Development was followed longitudinally and scored as embryonic stage at the end of the exposure, hatch time, hatching probability (mortality), body length, postembryonic stage, and egg‐laying pattern. The rate of in vivo embryonic development was observed hourly for 24 hours covering times before, during, and after EtOH exposure. Results After exposure to 10% EtOH, embryos were at younger embryonic stages, hatched later, and had higher mortality compared to unexposed controls. Embryos exposed to 5% EtOH were at normal embryonic stages, showed no change in mortality, but hatched later than controls. Both EtOH groups showed shorter mean body lengths and slower postembryonic development; however, the 5% group recovered to control levels faster than the 10% group. The pattern of egg laying was delayed in the 10% group, but not in the 5% group. Hourly in vivo observations revealed that a developmental delay was first visible a few hours into 10% EtOH exposure and that the delay increased after the removal of EtOH exposure. Conclusions Developmental delays occurred during and immediately after exposure and were not uniform but rather dynamic. This article highlights the importance of investigating EtOH‐induced defects using different markers and at multiple time points. Attention to temporal effects during and immediately after EtOH exposure can provide understanding of these sensitive time points for observation and treatment.

Embryonic Methamphetamine Exposure Inhibits Methamphetamine Cue Conditioning and Reduces Dopamine Concentrations in Adult N2 <b><i>Caenorhabditis elegans</i></b>

“…Since most neurogenesis occurs during embryogenesis in C. elegans , MAP exposure was conducted during this critical period of neurobiological development. Other researchers have utilized similar exposure paradigms to examine the effects of embryonic drug exposure on development in C. elegans [57]. It is well established that MAP is neurotoxic to DA neurons and can lead to neurodegeneration in mammals [15], and the data presented here indicates that similar effects can occur in C. elegans .…”

Unraveling the Mechanisms of Behaviors Associated With AUDs Using Flies and Worms

“…Chronic exposure to EtOH in C. elegans results in delayed development, decreased reproduction, and shortened life span (Davis et al., ). Depending on the time point of EtOH exposure, defects in development vary in strength, suggesting that C. elegans could be used to identify the critical period during development at which EtOH exposure causes subsequent delays (Lin et al., ). In Drosophila , EtOH exposure during development results in reduced viability, slower development, and a reduced rate of neuroblast division, resulting in smaller brains.…”

A Comparison of the Different Animal Models of Fetal Alcohol Spectrum Disorders and Their Use in Studying Complex Behaviors

“…However, if ethanol is applied at a 0.4 M concentration, previous studies in adult C. elegans have shown that an internal ethanol concentration equivalent to 100 mg/dl can be reached (146). In studies that have used this model to examine the effects of ethanol on development, ethanol exposure produced, in a dose-dependent manner, significant growth retardation, slowed the developmental process, impaired reproduction, and lead to early demise in the offspring (145, 147) indicating that ethanol can have similar effects on development in C. elegans as in human beings. Future work using this model may be able to shed light into some of the genetic mechanisms of PNEE, and whether particular genes may confer sensitivity or resistance to the toxic effects of ethanol during development (145, 147).…”