UC Riverside

Fetal alcohol spectrum disorders (FASD) describe the wide array of long-lasting developmental abnormalities in offspring due to prenatal alcohol (ethanol [EtOH]) exposure via maternal gestational drinking. Our laboratory has identified many deleterious effects of prenatal ethanol exposure (PrEE) as well as paternal ethanol exposure (PatEE) prior to conception in a mouse model. Our results indicate that PrEE and PatEE can have substantial effects on the offspring including alterations in gross anatomy, neuroanatomy, gene expression, and behavior. In chapter 1, we show that PrEE can lead to craniofacial anomalies, decreased body weight and length, decreased brain weight and cortical length, as well as structural changes to the cortex and corpus callosum in embryonic development (E12.5, E14.5, E16.5, E18.5). To further explore potential heritable effects of PrEE, we investigated brain and behavioral development in the F1 (directly-exposed), F2 (indirectly-exposed) and F3 (non-exposed) generations in Chapter 2. All generations of PrEE newborns had decreased body weights, brain weights, and neocortical lengths compared to controls, although there were no differences in brain to body weight ratios. Hippocampal CA3 was significantly thinner in all generations of PrEE mice compared to controls. PrEE resulted in a significant rate of agenesis or partial development of the corpus callosum in the majority of F1 cases, with a less frequent, non-significant, occurrence in F2 and F3 mice. Disrupted sensorimotor integration, motor control, and anxiety-like behavior persisted to at least the F2 generation. In Chapter 3, we investigated the transgenerational effects of paternal EtOH exposure (PatEE) on offspring brain and behavioral development. We observed no differences between control and PatEE (F1 and F2) mice in measures of neocortical length. Abnormal patterns of Id2 and RZRβ gene expression were observed in the F1 generation but not the F2 at P0. Additionally, PatEE may generate sex-specific effects on offspring behavior that can last up to two generations after the sire’s initial exposure. We propose that the effects of drinking alcohol during pregnancy or prior to conception may be more serious than previously thought as transgenerational effects were observed in the offspring even though they never consumed alcohol themselves.