The consequences of alcohol consumption during pregnancy Essay

Alcohol consumption during pregnancy leads to shortcomings in the development of the fetus. Fetal Alcohol Syndrome is the most common birth defect caused by teratogen exposure in the early developmental stages. This prenatal exposure to alcohol (PEA) causes lifelong cognitive and behavioral deficits (Smith et al., 2014). PEA impairs neurodevelopment through decreasing the neural cell proliferation, survival, migration and differentiation, which results in craniofacial dysmorphology. The severity and likelihood of advancement in abnormalities are dependent on the stage in embryological development, timing, dosage, genetics and other environmental factors.
The neural crest cells formed from the neuro-epithelial cells at the end of the first month of pregnancy in humans is the essential for craniofacial development. These cells are multipotent and are sometimes referred to, as "stem-cell" like cells. These defects eventuate from disruptions in the Sonic Hedgehog (Shh) signaling pathway, cytoskeletal development of neural crest cells and Wnt/-Catenin pathway essential for differentiation, migration and proliferation (Vangipuram and Lyman, 2012). During embryological development, there are frequent apoptotic mechanisms occurring to remove unwanted cells. Exposure to alcohol seems to eliminate neural crest cells from the hindbrain segment by inducing programmed cell death that interferes with facial development (Cartwright et al., 1998 Vangipuram and Lyman, 2012). Alcohol has a plethora of cell surface receptors hence, the exact mechanism through which it effects the neural crest cells is still unknown.
Sonic Hedgehog is essential for early stages of development and is found in the play a fundamental role in proliferation, differentiation and directional guidance (Ingham and McMahon, 2001). The secretion of protein, Sonic hedgehog (shh) is essential for specification of multiple events such as specification of brain, facial and oral structures imperative for craniofacial development (Ahlgren et al., 2002). Shh acts a guide molecule for neural crest cells during embryological stages (Tolosa et al., 2016). Shh mutations in humans, mice and chick embryo's have been shown to cause significant flaws in the head and facial regions (Ahlgren et al., 2002 Smith et al., 2014). However, it has been postulated that ethanol activates protein kinase A (PKA) in prechordal mesendoderm (PME) cells which in turn suppresses the expression of Shh as PKA is an antagonist for Sonic Hedgehog signaling (Aoto et al., 2002 Smith et al., 2014).
Exposure to alcohol leads to a disruption in the actin cytoskeleton of the neural crest cells, thereby thickening and fragmenting the cell-to-cell connections eliciting collapse of neural crest cells. The actin dependent migratory mechanism is distorted due to ethanol preventing the polymerization of F-actin necessary for focal adhesions during migration. (Oyedele and Kramer, 2013) Alcohol also leads to downregulation of -catenin levels which are an important component of adheren junctions also effect the migration pattern of cranial neural crest cells (Kiecker 2016).
The WNT signaling pathway is inhibited by subjection to alcohol and is thought to induce apoptosis. The consequences of exposure to alcohol inducing apoptosis and disruptions in migrations of neural crest cells are a combination of different mechanisms and cannot be solely attributed to interruption of a single defined pathway.