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Developmental Timeline of Alcohol-Induced Birth Defects
[1]
By: O'Neil, Erica Keywords: Fetal alcohol syndrome [2] Human development [3]
Maternal consumption of alcohol (ethanol) during pregnancy [5] can result in a continuum of
embryonic developmental abnormalities that vary depending on the severity, duration, and
frequency of exposure of ethanol during gestation [6]. Alcohol is a teratogen, an environmental
agent that impacts the normal development of an embryo or fetus [7]. In addition to doserelated concerns, factors such as maternal genetics and metabolism and the timing of alcohol
exposure during prenatal development also impact alcohol-related birth defects [8].
Fetal Alcohol Syndrome [9] (FAS) is the most severe collection of alcohol-related birth defects [8]
, and is defined by pre- and post-natal growth retardation [10], minor facial abnormalities, and
deficiencies in the central nervous system [11] (CNS). The effects of alcohol on prenatal
development can include much more than those defining criteria, however, and prenatal
exposure to alcohol can potentially impact normal development at almost any point in the
pregnancy [5], from embryonic through fetal development.
Prenatal development has into two stages, the embryonic stage that comprises the first eight
weeks of development after fertilization [12], and the fetal stage that encompasses the
remainder of development. The embryonic stage is the period when body plans are laid out,
and the precursors of what will become organ systems are determined. Alcohol introduced at
this stage can have significant repercussions depending on the population of cells negatively
affected. Those developmental deviations can result in a range of birth defects [8] or may
completely arrest the pregnancy [5] if malformations are particularly severe. During the fetal
stage, prenatal alcohol exposure still has the potential to negatively impact development, but
much less than the massive developmental defects that can result from exposure during the
embryonic stage.
In the first two weeks following fertilization [12], excessive alcohol consumption does not
generally have a negative effect on the zygote [13] and emerging blastocyst [14] (pre-embryo).
Maternal consumption of alcohol during this time can prevent proper implantation [15] of the
blastocyst [14] in the uterus [16], resulting in an increased rate of resorption or early termination
of the pregnancy [5], generally before a woman realizes she is pregnant. The potential for the
cells in the blastocyst [14] to become any cell lineage [17] in the body generally confers
protection against the negative effects that alcohol has on specific cellular populations.
It is in the third week after fertilization [12] that specific alcohol-induced birth defects [8] begin to
affect the developing embryo. At this point in the developmental timeline, gastrulation [18]
commences and the three embryonic germ layers [19] (ectoderm [20], mesoderm [21], and
endoderm [22]) are set. Between this point and the sixth week after fertilization [12], when
neurulation [23] occurs, the cranial neural crest [24] cell population is vulnerable to alcoholinduced damages. The cranial neural crest cells [25] compose the frontonasal process of the
developing embryo, which interacts with the ectoderm [20] to differentiate into facial features.
Damage to this cellular progenitor pool can result in the minor midline facial abnormalities
characteristic of FAS.
Precursor cells that give rise to the heart also begin to differentiate shortly after the third week
and by the fourth week of development, the embryonic heart is already beating. During this
rapid period of cardiac development, alcohol can impede the proliferation, migration, and
specification of cardiac progenitor cells by prompting either a deficient or toxic levels of retinol
(vitamin A) in the developing embryo. Defects that result from those impediments can include
atrial and ventricular abnormalities, issues with valve formation, and a potential increase in the
risk of heart disease later in adulthood.
The neural plate [26] forms in the third week, the anterior portion of which gives rise to
neuroectoderm, tissues fated to form the tissues of the central nervous system [11] (CNS).
From this point through the third trimester [27], the cellular progenitor pools, called radial glia [28]
, that will give rise to the CNS become vulnerable to the effects of alcohol. The radial glia [28]
signals the creation and migration of neurons and their support cells (glia [29]) during
development. Damage to this cellular pool can result in morphological abnormalities and an
overall reduction [30] in white matter [31] within the brain. Alcohol also impacts the mechanisms
and signaling pathways responsible for the creation of those brain cells, impeding cellular
proliferation, differentiation [32], and survival.
During the third week of gestation [6], ocular development begins and tissues of the eye are
the first component of the central nervous system [11] compromised by the prenatal
introduction of alcohol. During this time and continuing forward, the retina becomes vulnerable
to the effects of alcohol. At about four weeks after fertilization [12], the neuroectoderm begins to
interact with the surface ectoderm [20] to create tissues that later give rise to the lens and
cornea of the eye. In the fifth week following fertilization [12], the mesoderm [21] surrounding the
developing eye begins to give rise to the uvea (iris and other associated muscles), sclera
(protective sheath surrounding the eye) and eyelids. The most common defects,
microphthalmia and optic nerve hypoplasia [33] arise when prenatal alcohol exposure
compromises this developmental cycle.
Specific damage to the brain can continue in the sixth and seventh week following fertilization
[12], after the brain has begun to divide into vesicles. At that point, the corpus callosum [34], a
midline structure responsible for the communication between the left and right hemispheres of
the brain, becomes vulnerable to alcohol. Prenatal alcohol exposure can result in the
underdevelopment or complete agenesis of that structure, which is composed primarily of
myelinated axons, and is therefore extremely vulnerable to ethanol?s impact on radial glia [28]
progenitor pools.
The eighth week after fertilization [12] is the end of the embryonic stage and the beginning of
the fetal stage of pregnancy [5]. Prenatal alcohol exposure still has the potential to negatively
impact normal development, but as the majority of organ systems have been determined by
this point in time, organ-specific birth defects [8] are not normally expected. The developing
central nervous system [11] remains vulnerable to the prenatal exposure of alcohol, particularly
in the formation of the cerebellum [35], and the fetus [7] remains vulnerable in terms of prenatal
growth restrictions.
The cerebellum [35] is one of the last structures of the brain to differentiate during development,
with the majority of structures in the brain having begun development earlier. Most cellular
proliferation, migration, and synaptic regulation [36] in the cerebellum [35] occur in the third
trimester [27], 24 weeks after fertilization [12] through birth. This period of intense neuronal
creation, organization [37] and connectivity is called the brain growth spurt [38]. While the radial
glia [28] progenitor pool has already been established by this point in time, alcohol can still
impact neural migration and synaptogenesis [39].
The fetus [7] is not as sensitive to the effects of alcohol as is the embryo, and in the third
trimester [27] the fetus [7] begins to self-regulate and redirect resources to cope with
environmental damages. Self-regulation [36] is observed in the pre-natal growth deficiencies
that accompany FAS, which fall into two broad categories, symmetric or asymmetric
intrauterine growth restrictions. If alcohol impacts cellular proliferation in the first and second
trimester [27], or consistently throughout the entire pregnancy [5], then the growth deficiencies
will be symmetric and observed across all parts of the developing fetus [7]. Asymmetric growth
restrictions, which result in a normal-sized head but smaller than normal abdominal cavity,
may result in the third semester. The head is a normal size because in the third trimester [27]
the fetus [7] can redistribute cardiac resources to the command centers of the body, like the
brain and heart, at the expense of other less vital processes like digestion.
There is no point during development when prenatal alcohol exposure lacks consequences,
the occurrence of the more severe birth defects [8] correlates with exposure to alcohol in the
embryonic stage rather than the fetal stage. FAS and related alcohol-induced birth defects [8]
are an example of what can happen when a mother heavily imbibes alcohol during the course
of the pregnancy [5]. In the United States, the Surgeons General caution women against
drinking while pregnant and require warnings be displayed on all alcoholic products.
Sources
1. Armstrong, Elizabeth M. Conceiving Risk, Bearing Responsibility: Fetal Alcohol
Syndrome [9] & the Diagnosis of Moral Disorder. Baltimore: The John Hopkins University
Press, 2003.
2. Bookstein, Fred L., Paul D. Sampson, Paul D. Connor, and Ann P. Streissguth. ?Midline
Corpus Callosum is a Neuroanatomical Focus of Fetal Alcohol Damage,? The New
Anatomical Record 269 (2002): 162?74.
3. Dikranian, Krikor, Yue-Qin Qin, Joann Labruyere, Brian Nemmers, and John W. Olney.
?Ethanol-Induced Neuroapoptosis in the Developing Rodent Cerebellum and Related
Brain Stem Structures,? Developmental Brain Research 155 (2005): 1?13.
4. Gilbert, Scott. Developmental Biology [40], 8 ed. Sunderland: Sinauer, 2006.
5. Golden, Janet. Message in a Bottle: The Makings of Fetal Alcohol Syndrome [9].
Cambridge: Harvard University Press [41], 2005.
6. Grewal, Jagteshwar, Suzan L. Carmichael, Chen Ma, Edward J. Lammer, and Gary M.
Shaw. ?Maternal Periconceptional Smoking and Alcohol Consumption and Risk for
Select Congenital Anomalies,? Birth Defects Research Part A: Clinical and Molecular
Teratology 82 (2008): 519?26.
7. Guerri, Consuelo, Alissa Bazinet, and Edward P. Riley. ?Foetal Alcohol Spectrum
Disorders and Alterations in Brain and Behavior,? Alcohol & Alcoholism 44 (2009):
108?14.
8. Rubert, Gemma, Rosa Miñana, Maria Pascual, and Consuelo Guerri. ?Ethanol
Exposure during Embryogenesis Decreases the Radial Glial Progenitor Pool and Affects
the Generation of Neurons and Astrocytes,? Journal of Neuroscience Research 84
(2006): 483?96.
9. Saito, Toshikazu, Boris Tabakoff, Paula L. Hoffman, Kim Nixon, Masaru Tateno, and
Consuelo Guerri. ?The Effects of Ethanol on Neuronal and Glial Differentiation and
Development,? Alcoholism: Clinical and Experimental Research 29 (2005): 2070?75.
Maternal consumption of alcohol (ethanol) during pregnancy can result in a continuum of
embryonic developmental abnormalities that vary depending on the severity, duration, and
frequency of exposure of ethanol during gestation. Alcohol is a teratogen, an environmental
agent that impacts the normal development of an embryo or fetus. In addition to dose-related
concerns, factors such as maternal genetics and metabolism and the timing of alcohol
exposure during prenatal development also impact alcohol-related birth defects.
Subject
Fetal alcohol syndrome [42] Fetal Alcohol Syndrome [43]
Topic
Disorders [44] Reproduction [45]
Publisher
Arizona State University. School of Life Sciences. Center for Biology and Society. Embryo
Project Encyclopedia.
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© Arizona Board of Regents Licensed as Creative Commons Attribution-NonCommercialShare Alike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-ncsa/3.0/
Format
Articles [46]
Last Modified
Wednesday, June 22, 2016 - 21:30
DC Date Accessioned
Thursday, May 10, 2012 - 14:06
DC Date Available
Thursday, May 10, 2012 - 14:06
DC Date Created
2011-04-24
DC Date Issued
Thursday, May 10, 2012
DC Date Created Standard
Sunday, April 24, 2011 - 07:00
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[4] https://embryo.asu.edu/search?text=Developmental%20Timeline%20of%20AlcoholInduced%20Birth%20Defects
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