Teratogenic+Effects+of+Alcohol+&+Nicotine

** Teratogenic Effects of Alcohol & Nicotine ** Jontae Huck, Margo Larsen, Nina Johnson & Rebecca Rose ** Introduction ** Both alcohol and nicotine are teratogens. Teratogens are environmental agents that affect the normal development of an embryo or fetus. Alcohol and nicotine consumption during pregnancy can result in developmental abnormalities. The severity of birth defects caused by the consumption/use of alcohol and nicotine during gestation varies depending on the exposure time, dosage amounts, maternal genetics and frequency of use. To avoid the negative impacts associated with both teratogens, do not use them at any point during pregnancy. Both cause devastating effects when consumed/used at any stage of pregnancy, so the best way to avoid impact is to avoid their use at all costs. Both teratogens have differing effects on developmental processes and each will described separately below.

**ALCOHOL**

** Normal Human Development Affected by Alcohol ** Alcohol consumption can affect the developing embryo/fetus all throughout pregnancy. Different anomalies arise depending on the time of alcohol exposure. To understand how alcohol affects development, an understanding of the normal progression of the developmental process is required. For our purposes, we will describe the normal progression of development starting with the formation of the bilaminar germ disc. Alcohol consumption during and/or prior to forming the bilaminar germ disc causes devastating disruptions in normal developmental progression.  The epiblast normally forms when the inner cell mass of the morula delaminates into the bilaminar germ disc. The bilaminar germ disc consists of both the epiblast and the hypoblast cell layers. The primitive streak forms on the surface of the epiblast. Cells normally migrate through the primitive streak of the epiblast to form the centrally located mesodermal layer during the process of gastrulation. After gastrulation takes place, a trilaminar germ disc has formed which contains the three germ layers. The three germ layers are the ectoderm, mesoderm, and endoderm. The ectoderm and mesoderm germ layers are derived from the epiblast cells, while the endodermal germ layer is derived from both the epiblast and hypoblast cells (Chaudhuri, 2000). After the three germ layers are established, the development of the various organ systems takes place. Normally, the ectodermal germ layer gives rise to the nervous system, inner eye structures, as well as the epidermis layer of the skin. The mesodermal layer normally gives rise to the muscular, skeletal, and urinary systems. The cardiovascular system is derived from the mesenchymal cells of the mesodermal germ layer as well. The endodermal germ layer gives rise to the gastrointestinal system as well as internal linings of other organ systems (Chaudhuri, 2000). Alcohol has been shown to affect the normal development of the epiblast cell layer, which has the potential to affect development of all of the major organ systems. Alcohol has also been shown to inhibit the migration of cells through the primitive streak (Nakatsuji & Johnson, 1984). Even though alcohol can disrupt the normal formation of potentially every organ system, it appears as if the brain and heart are more affected than any other system. The reasons behind this have yet to be determined. Previous studies have also revealed that mesodermal derived structures are affected by prenatal alcohol exposure. It is thought that either the damage done to the epiblast or the inhibition of proper gastrulation migrations may be responsible. Both effects can be responsible for the malformations and it likely depends on when the developing embryo/fetus is exposed to alcohol (Chaudhuri, 2000). ** Effects of Alcohol on Development ** Fetal Alcohol Syndrome, also called FAS, is caused by the consumption of alcohol by an expectant mother. In the United States, an estimated 1 of every 1000 live births will have some sort of effects from alcohol consumption during various points in the pregnancy. It is most common in Native Americans and low income families. FAS has a number of symptoms which vary in severity. FAS is a common cause of non-genetic mental retardation. Characteristics that are generally associated with this syndrome are often noticed in facial features. These include a small head, small eyes, thin upper lip, an upturned nose, and a very small skin surface between the upper lip and the nose. Often, deformed joints and limbs are a result of this syndrome as well. Generally, those suffering from FAS will have stunted growth prior to birth. After birth, this issue persists. Other problems after birth may include vision difficulties, hearing issues, mental retardation, delayed development, learning disabilities, attention deficit disorder, hyperactivity, anxiety, and heart defects.

** Alcohol's Mechanisms of Alteration **

Alcohol has neurological effects on anyone who consumes it. However, when the unborn fetus is so small, any amount of alcohol can cause extremely adverse effects. Research on FAS is still relatively limited because the opportunity to study on a human is rare. Much of the research is done on laboratory animals. Although any amount of alcohol can cause defects in the unborn child, binge drinking has proven to cause the most serious consequences. Binge drinking results in a much higher blood alcohol concentration, which is even more damaging to the fetus. Alcohol is transported through the body in the blood. It interacts with various membrane binding molecules. One of these is N-methyl-d-aspartate receptor, otherwise called NMDA. NMDA, in a normal situation, is activated by glutamate. It is important for neural development as well as learning throughout the lifetime. Alcohol over activates the NMDA. This increases the internal calcium level of the neurons and cause death of the cells (Tsai & Coyle, 1998).

As well as its affects on the membrane binding receptors, alcohol affects the production of neurotrophic factors. The neurotrophic factors play a part in cell metabolism, growth, proliferation, differentiation, migration and maturation. During fetal development, alcohol can deter the production of these factors. Another affect that alcohol has on them causing them to respond incorrectly to their regular trigger factors. Included in the neurotrophic factors that are affected by alcohol are insulin-like growth factor, nerve growth factor, basic fibroblast growth factor, brain derived neurotrophic factor, and the glial derived neurotrophic factor. The insulin-like growth factor normally works for positively for proper cell metabolism and growth, promotes proliferation and differentiation, and signals the neurons and glia to matures. Also, it keeps cells from undergoing apoptosis. The nerve growth factor is used for the survival and maintenance of sympathetic and sensory neurons. The basic fibroblast growth factor is used to control the formation of angiogenesis as well as promoting neuronal survival. The brain derived neurotrophic factor and the glial-derived neurotrophic factor promote survival and differentiation of neurons and may have a role in the preventation of apoptosis. When alcohol is introduced to the fetus, the amounts of neurotrophic factors are decreased significantly. Thus, many of these crucial processes they are responsible for are jeopardized (Tsai & Coyle, 1998).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Another way in which alcohol can cause cell death is by causing oxidative stress. This is when there is an imbalance between the amount of reactive oxygen and the amount of antioxidants. When alcohol causes apoptosis, an increased amount of reactive oxygen is present. However, there is not a high enough level of the antioxidants to protect the remaining cells. Thus, there is additional cell death. When cells are attempting to become mature neurons, they are exceptionally susceptible to death due to alcohol introduction. This displays why victims of FAS have typical symptoms. Migration of neurons is inhibited by alcohol which is why development is often stunted. Cells from the cranial neural crest migrate to their specified location in order to form facial cartilage, facial bones, and peripheral nerves of the cephalic region. Fetuses exposed to alcohol before these features are formed will show typical facial characteristics of FAS (Tsai & Coyle, 1998).

<span style="font-family: Arial,Helvetica,sans-serif;">** Timing of Alcohol's Teratogenic Effects **

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">As alluded to previously, alcohol can affect the development of an embryo/fetus at any point during pregnancy. Alcohol exposure can affect development both prenatally as well as postnatally. Prenatal development is typically divided into two stages, the embryonic stage and the fetal stage. The embryonic stage includes the first eight weeks after fertilization. The fetal stage includes the rest of development that takes place after eight weeks up until birth (O’Neil, 2011). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Alcohol consumption during the embryonic stage results in massive developmental defects and has much more severe repercussions than alcohol consumption during the fetal stage. However, consumption during the fetal stage still negatively affects normal developmental processes (O’Neil, 2011). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Alcohol consumption during the first two week after fertilization appears to have the least destructive effects on the zygote. Excessive consumption during the first two weeks, however, can prevent proper implantation into the uterine lining. In addition, excessive consumption during this stage increases the likelihood of early termination of pregnancy where the blastocyst previously, successfully implanted into the uterus (O’Neil, 2011). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">The third through sixth week after fertilization are very susceptible to alcohol-induced malformations. This is the point in development when the three germ layers previously discussed start to produce specific cell lineages and start to determine organ systems. Neurulation also takes place during this period. The products of neurulation, such as the neural tube and neurons, are very vulnerable to damage caused by alcohol consumption (O’Neil, 2011). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Many of the organ systems are determined during the embryonic stage of development which is why alcohol consumption within the first eight weeks after fertilization is especially dangerous. The fetal stage of development is also susceptible to damage. During the fetal stage, the central nervous system remains vulnerable to alcohol-induced damage (Spohr, Willms, & Steinhausen, 1993). Growth is also stunted during the fetal stage due to alcohol consumption. Overall, the fetus is not as sensitive to alcohol exposure as the embryo. This is because at this stage, the fetus can start to self-regulate maternal intake molecules. By self-regulating, the fetus can somewhat cope with the damages caused by alcohol. However, the fetus often can only redirect the damage to less vital systems, like the digestive system, in order to protect the brain and heart. If the digestive system is compromised, the fetus cannot obtain adequate nutrients needed for growth (O’Neil, 2011). <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Alcohol has devastating effects on development during both the embryonic and fetal stages. Alcohol more severely affects the embryonic developmental stage, but still negatively affects the fetal developmental stage. Alcohol is NEVER safe to consume at any stage during pregnancy.

<span style="font-family: Arial,Helvetica,sans-serif;">** Possible Treatments for Teratogenic Effects of Alcohol **

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">If alcohol is used during pregnancy and results in FAS, treatments are useless since there are no cures for FAS after the fact. However, during the development of the embryo/fetus there are various treatments that can be used to reduce the teratogenic effects of alcohol. These various treatments fall into multiple categories such as N-methyl-d-aspartate receptor antagonists (NMDA), serotonin agonists, antagonism of alcohol effects on L1 cell adhesion molecules, neurotrophic factors, antioxidants, and nutritional factors.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">Within the NMDA catagory it has been found that the adminstration of NMDA receptor antagonists can lower the teratogenic effects of alcohol. These NMDA antagonists include MK-801, agmatine, eliprodil, and memantine (Idrus & Thomas, 2011). In a study conducted by Idrus and collegues (2011) the use of memantine lowered the motor coordination effects that came from alcohol use. This is turn reduced the cerebellar neuronal loss because memantine blocks the NMDA receptor overactivation without blocking neurotransmission. With this evidence, blocking the NMDA receptors during withdrawl time may reduce the prenatal teratogenic effects from alcohol. This possible treatment for FAS needs to be researched in greater depth; however, it is one option to decrease the teratogenic effects alcohol.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">The next treatment category for teratogenic effects from alcohol is the serotonin antagonists. Serotonin is known to act like a neurotransmitter. It has also been found to increase neuronal growth also. A study conducted by Druse and colleagues (2004) found that administering serotonin antagonists can prevent apoptosis (cell death that occurs from the alcohol) and the loss of neurons and glia from the brain. It was shown that during development, alcohol significantly decreases the 5-HT neuronal number (specific neurons), therefore by adding more serotonin it is possible to increase the production of anti-apoptotic proteins (Lee et al., 2009).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">Another treatment category that has antagonism, relates to the effects of alcohol on the L1 cell adhesion molecules. L1 cell adhesion molecules are used for communication and proper development of neurons. Types of alcohols such as 1-octanol have the ability to interrupt ethanol's action on L1 adhesion. 1-octanol and other alcohols have been found to prevent ethanol-induced cell death, growth retardation, and neural tube closure delays (Chen et al., 2001). Along with 1-octanol, certain peptide fragments can reduce the teratogenic effects from alcohol. These fragments include the activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF) (Wilkemeyer et al., 2002). Each of these antagonists have the capability to protect the neurons, prevent fetal death, and reduce neural tube defects that are found with alcohol use during pregnancy.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">Another category of treatments relates to neurotrophic factors. Neurotrophic factors include factors that deal with the insulin-like growth factor, nerve growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, and glial-derived neurotrophic factor (Climent et al., 2002). Having these factors present increases the possibilty of normal growth, therefore adminstration of these factors could possibly decrease teratogenic effects of alcohol (Mitchell et al.,1999). Not much information can be found on why neurotrophic factors aid in FAS; however, it is being researched further.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">The next type of treatment available is the administration of certain antioxidants. These antioxidants have agents such as resveratol, curcumin, and epigallocatechin-3-gallate that have been found to block alcohol's teratogenic effects (Antonio & Druse, 2008). Other studies have found that antioxidant vitamins such as vitamin E, vitamin C, and vitamin A can also block alcohol's teratogenic effects (Cohen-Kerem & Koren, 2003). Supplementing these antioxidants into the body at sufficient levels can definitely help prevent the devastating effect of FAS; however, it is important to not over use the antioxidants because it can cause problems elsewhere.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px; line-height: 24px;">The last category of treatments, which is an aspect that should be monitored throughout pregnancy anyways, are nutritional factors. Nutritional factors such as zinc, folate, and choline have been found to protect against alcohol's teratogenic factors. According to Summers et al. (2008 & 2009), zinc protects against postnatal mortality, dysmorphology, and cognitive impairments. Zinc and folate supplementation lowers problems with growth retardation, physical characteristics, and neuronal loss (Wang et al., 2009). It has also been found that prenatal choline supplementation will lower the teratogenic effects of alcohol-related lower birth weight, physical anomalies, and behavioral development (Thomas et al., 2009).

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 21.33px; text-align: center;">**NICOTINE**

<span style="font-family: Arial,Helvetica,sans-serif;">** Normal Human Development Affected by Nicotine **

//<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Normal Lung Development** //

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Since nicotine has numerous effects on the developing embryo/fetus, we have chosen to focus on the teratogenic effects nicotine has on lung development and gestational weight gain. As with the teratogenic effects of alcohol, to properly understand the anomalies, it is necessary to understand the normal events of development first. <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Lung development is a very lengthy process that starts during the organogenesis stage and ends at some point during early childhood. The entire process of lung development can be divided into five main phases. The time frame of each phase is outlined below (Post & Copland, 2002).
 * 1) <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Embryonic Phase** - day 26 - day 52
 * 2) <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Pseudoglandular Phase** - day 52 - end of 16 weeks of gestation
 * 3) <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Canalicular Phase** - 17 weeks - 26 weeks of gestation
 * 4) <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Saccular Phase** - 24 weeks - 36 weeks to term
 * 5) <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Alveolar Phase** - 36 weeks to term and at least 36 months postnatal

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">The lung buds start to appear in the embryonic phase. They appear as tracheal outgrowths from the foregut. During the pseudoglandular phase, the airway epithelium starts to differentiate. Neuroendocrine cells, ciliated cells, as well as goblet cells also start to appear during this phase (Jeffery, 1998). Mesenchymal cells also start forming the cartilage and smooth muscle cells of the lungs during the pseudoglandular phase. At approximately 8 weeks of development, fetal breathing movements start to become discernible (Post & Copland, 2002). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">During the canalicular phase, air way branching is completed and the future gas exchange regions of the lungs start to develop. Also during this phase, bronchioles start to appear, vascularization increases and cells start receiving signals to start producing surfactant (DiFiore & Wilson, 1994). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">During the saccular phase, lung development starts preparing for the non-uterus environment. During this phase, pulmonary parenchyma continues to grow, connective tissue between airspaces starts to thin and the surfactant producing cells continue to mature (DiFiore & Wilson, 1994). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">At birth, the lung is functional but it is still immature. The lungs are considered immature because the functional alveoli units are still undeveloped. The alveoli form during the alveolar phase. The formation of alveoli lasts into early childhood and greatly increases the surface area for gas exchange (Burri, 1984). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">//**Normal Gestational Weight Gain**// <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Gestational weight gain is another area of development that is also affected by nicotine exposure. Normally, weight gain functions to support the growth and development of the fetus, but nicotine exposure causes nutrient acquisition and weight gain to be hindered which results in low birth weights (Rassmussen & Yaktine, 2009). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Gestational weight gain is influenced by maternal physiology, maternal metabolism and placental metabolism. The placenta plays a key role in gestational weight gain since it functions as both a barrier and a transporter of substances between the mother and the fetus. The fetal growth rate can be impacted by the maternal environment as well as changes in the maternal homeostasis mediated via the placental transport structure (Rassmussen & Yaktine, 2009). <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">In single-baby pregnancies, normal fetal growth is uniform until about the middle of the second trimester. From that point on, up until birth, fetal weight gain increases significantly. With single-baby pregnancies, growth rates are highest during the third trimester. In multiple-baby pregnancies, growth rates are similar to single-births up until about the 30 week mark. Compared to single-birth fetuses, multiple-birth fetuses experience an overall decrease in fetal weight gain during the third trimester (Rassmussen & Yaktine, 2009). <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;">** Effects of Nicotine on Development ** ====<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Nicotine has long been known to have teratogenic effects on embryos, but as time goes on and research progresses more and more detrimental consequences to fetal development continue to be discovered. Use of products containing nicotine during pregnancy greatly increase the chances of miscarriage, impede lung and brain development, alter signaling pathways and paracrine factor levels in the fetal environment, produce problems with placental attachment and blood flow, and are associated with low birth weight babies, premature births, cleft palates, Sudden Infant Death Syndrome (SIDS), increased cancer risk, cognitive impairments and behavioral disorders (Maritz & Harding, 2011; Wickström, 2007). This report will focus on nicotine’s contributions to low birth weight and increased cancer risk in the lungs. ====

<span style="font-family: Arial,Helvetica,sans-serif;">** Nicotine's Mechanisms of Alteration **

//<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Altered Lung Development** //

After crossing the placenta, nicotine interacts with nicotinic acetylcholine receptors on the cells of various body tissues, causing changes within those cells and altering the normal pattern of development. Compounding the problems that nicotine creates in the first place, many acetylcholine receptor subunits have been shown to be up regulated in fetal lungs exposed to maternally ingested nicotine. The types of subunits that a receptor consists of determine the signaling cascade it sets off in a cell. In addition to increasing the number of nicotinic receptors present in the lung, studies have shown that the affinity these receptors have for nicotine increases with early nicotine exposure. Together, these increase the sensitivity the lungs have to nicotine. If this sensitivity lasts after birth, the effects of nicotine exposure to the lungs will continue to be amplified (Maritz & Harding, 2011).

The specific signaling mechanisms and molecules that nicotine induces in fetal lung tissues aren't entirely known, but several outcomes of these cascades have been discovered. Receptors known to be upregulated by nicotine are responsible for regulating the shape and structure of cells and the contact that they make with neighboring cells. Consequently, the complex organization of lung parenchyma is disrupted in fetuses exposed to nicotine, as seen in Figure 3. The alveoli of the parenchyma were found to be larger and more loosely organized in post-natal rats exposed to nicotine in the womb. Because they are the essential subunits that facilitate gas exchange, disruption of normal alveolar surface area and organization results in less than optimal oxygen diffusion to the blood vessels and delivery to the tissues. The fetal development of the lung's connective tissue framework has also been shown to be impaired, see Figure 4. Rats and monkeys exposed to nicotine during development were born with lungs whose connective tissue looked much older and unhealthier than standard models (Maritz & Harding, 2011). It is thought that this increase in connective tissue is due to activation of fibroblasts by nicotine (Sekhon et al., 2004).

In addition to affecting the parenchyma and connective tissue within the lungs themselves, studies are now finding that fetal nicotine exposure alters the development of connective tissue in airway associated blood vessels. Specifically, the tunica adventitia is thicker in mammals born after being exposed to both low and higher levels of nicotine in utero. Generally, vessels associated with alveoli and lung tissue are composed on flat, thin cells in order to provide for optimal gas diffusion. This nicotine-induced thickening further impedes and impairs lung function by decreasing the rates and efficiency of oxygen diffusion into the blood and carbon dioxide release from the tissues (Sekhon et al., 2004).

Prenatal exposure to nicotine also greatly increases the chances of developing lung cancer. Nicotine disrupts normal genetic regulation and contributes to DNA damage. Cyclin D is a protein that helps cells get through the G1 checkpoint of the cell cycle, and nicotine exposure has been shown to increase the levels of cyclin D in lung cells, allowing them to jump this regulation step and divide unchecked. Nicotine has also been shown to increase the production of reactive oxygen species, molecules that are known to cause DNA damage. In addition to increasing the amounts of cyclin D found in the lung and levels of reactive oxygen species, nicotine over activates several kinases that are known to be associated with lung carcinomas, including protein kinase C and Raf-1. Both of these kinases are responsible for phosphorylating Bcl2. Phosphorylated Bcl2 disrupts the normal apoptotic process the body initiates to try and kill off cells with unregulated cell division. Nicotine also increases the phosphorylation of Akt in fetal lungs, activating survival pathways that, with the increase in PKC, Raf-1, cyclin D and ROS, contribute to a more favorable environment for the unregulated cell division that leads to cancer formation (Maritz & Harding, 2011).

//<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">**Decrease in Birth Weight** //

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Medically speaking, a baby born at a low birth weight weighs less than 2500 grams, or five and a half pounds. Nicotine exposure, whether through smoking or other means, is known to contribute to babies being born at or below this weight. The exact sequence of events that nicotine sets off leading to decreased weight gain isn’t known, but there are several plausible possibilities (Van Meurs, 1999).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">First, nicotine has been shown to cause the placenta to detach from the uterine wall, in most cases causing complete detachment and resulting in the death of the fetus. However, in cases when the placenta does not completely detach it’s likely that the placental-uterine connection is still impaired. Because the placenta is the route through which the fetus receives nutrients and oxygen from its mother, a block in this route would affect metabolism in the fetus and could contribute to the lower weights seen (Van Meurs, 1999).

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Another possibility is that the effect nicotine has on blood vessels is responsible for the low gestational weight. Nicotine has been shown to cause vasoconstriction in umbilical arteries supplying the fetus by reducing levels of prostacyclin, a vasodilating agent, and drastically increasing the levels of catecholamines, which are responsible for vasoconstriction. Nicotine is also known to affect the development of the baby’s own blood vessels, particularly pulmonary vessels, and impair lung function. All of these would result in low oxygen delivery to fetal tissues, again affecting metabolism and resulting in low birth weight (de Mello, Pinto, & Botelho, 2001).

<span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;">** Timing of Nicotine's Teratogenic Effects ** <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">Nicotine exposure is dangerous all throughout pregnancy and there is no point during pregnancy when nicotine is no longer teratogenic. The two main areas we focused on; lung development and gestational weight gain encompass nearly the entire term of pregnancy. Therefore, nicotine exposure at any point in the pregnancy can have long-lasting devastating effects on the developing embryo/fetus. <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;">As mentioned previously, lung development spans nearly the entire term of the pregnancy and even continues beyond birth into early childhood. Each phase of lung development outlined above is susceptible to nicotine exposure. Since lung development is an intricate process that occurs throughout a major span of the pregnancy, nicotine exposure at any point is potentially harmful (Post & Copland, 2002).

<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Nicotine’s effect on gestational weight gain also has devastating consequences all throughout pregnancy. Since a majority gestational weight is gained in the third trimester, nicotine exposure during this period is extremely harmful and causes lasting growth malformations throughout the entire life span of the child. However, nicotine exposure at any point during the pregnancy has negative effects. Nicotine affects the placenta causing it to separate from the mother, which decreases the placenta’s ability to absorb nutrients and gases. Disruption of the placental membrane can occur at any stage of pregnancy upon exposure to nicotine, so growth can be disrupted at any point due to the lack of adequate nutrient acquisition (Rassmussen & Yaktine, 2009). <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;">** Treatments For Teratogenic Effects of Nicotine ** <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;"> <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Treatments for the teratogenic effects of nicotine can only be summed up in one way, and that is to **not** use nicotine products during pregnancy. Nicotine, which comes in many different forms, has been found to cause developmental problems in various areas. For treatment there are no specifics, except keeping your nutritional factors in toll. Nutrition is very important in fetal development because it provides the stability and growth of the fetus. As found in treatments for tertogenic effects in alcohol it was stated that supplementation of zinc, folate, choline, and antioxidants such as vitamin E, C, and A were effective. Nicotine has a very similar impact on development, therefore, supplementing these important nutritional factors are important for treatment. <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;">** Conclusion ** <span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; text-align: left;">Alcohol and nicotine are teratogens that, unfortunately, are commonly used during pregnancy in the United States. As stated in the introduction, teratogens are environmental agents that affect the normal development of an embryo or fetus.Teratogenic effects from alcohol and nicotine can impact the development of the embryo/ fetus in multiple ways. These effects can include neuronal loss, physical impairments, retardation, lower birth weight, complications in organ development, and various other effects. While using alcohol or nicotine, timing can severely impact the problems that arise. The earlier these teratogens are used during pregnancy, the less likely it is that healthy development will occur. The only way to prevent any of these effects is to not use alcohol or nicotine during pregnancy. For those that do use these substances during pregnancy, some treatment options do exist, but there is no cure or assurance that the embryo/fetus will develop properly. The use of alcohol and nicotine during pregnancy always leads to devasting outcomes, therefore expecting mothers should **never** use these teratogens. <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;">** Works Cited ** <span style="display: block; font-family: Arial,Helvetica,sans-serif; text-align: left;"> <span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;"> Administrative staff. (2010). Regulation of nicotine containing products (NCPs). [Web page]. Retrieved from []

<span style="background-color: #ffffff; font-family: Arial,Helvetica,sans-serif; font-size: 16px;"> Antonio, A.M., & Druse, M.J. (2008). Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic neurons. //Brain Research,// //1204//, 16– 23.

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;"> Burri, P. H. (1984). Fetal and postnatal development of the lung. //Annual Review of Physiology, 46//, 617-628. doi:10.1146/annurev.ph.46.030184.003153

<span style="font-family: Arial,Helvetica,sans-serif; font-size: 16px;"> Chaudhuri, J. D. (2000). Alcohol and the developing fetus--a review. //Medical Science Monitor : International Medical Journal of Experimental and Clinical Research, 6//(5), 1031-1041.

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<span style="display: block; font-family: Arial,Helvetica,sans-serif; font-size: 16px; height: 1px; left: -40px; overflow-x: hidden; overflow-y: hidden; position: absolute; text-align: left; top: 6664.5px; width: 1px;">(Chaudhuri, 2000)