Lecture notes for Monday, January 26, 2015

Birth defects


Three percent of babies born in the United States have some structural abnormality.

These result from some failure of an embryological process.

For example, sometimes the neural tube does not close completely; The neural folds fail to fuse and seal off the neural tube. The result is called "spina bifida", which is Latin for the spine being split in two. That's because the net effect looks as if the sides of the neural tube had somehow been cut apart. (Photographs in Sadler, page 77)

Cleft lip, cleft palate, and most structural defects of the heart ("septal defects") are also caused by failure of normal fusions between masses of cells. For example, it sometimes happen that the right and left chambers of the heart fail to be separated by the sheets of cells that normally close them off from each other. It can also happen that the barrier does separate the two sides of the heart, but the barrier fuses at the wrong locations, causing major blood vessels to be connected to the wrong ventricles. (Pages 185-186 in Sadler).

Three other birth defects that result from failures of tissues to fuse are:

Coloboma, in which iris of the eye has a gap on its lower side, and the pupil is keyhole-shaped; This results non-fusion of the choroid fissure which is a groove in the optic cup where the optic nerve leaves the retina.

Cervical fistulas, which are holes connecting the back of the throat to the sides of the neck. These are remnants of the second, third and fourth "gill slits". Incidentally, the first pair of these openings normally remains open, and are called the eustachian tubes.

Oropharyngeal Membrane, which is a sheet of tissue in the back of your throat where the archenteron (invaginating from the posterior toward the anterior) meets the stomodeum (invaginating from anterior toward the posterior). Normally, this membrane disintegrates. That opens the connection from the throat to the esophagus, and to the lungs! If it fails to degenerate, then it has to be surgically cut away before the baby can begin to breathe.

These are not all of the examples of birth defects that result from failures of tissue fusions. Several more are listed, and graphically illustrated in Tom Sadler's excellent book. (p. 271, p 219)


Some general principles:

1) Anything that can go wrong, will go wrong. (sometimes).

2) Understanding normal embryological processes helps make sense of birth defects..

(Embryological knowledge eventually may be used to help cure some defects; For example, imagine the usefulness of a drug or other treatment that could stimulate fusion of epithelia in people with cleft lips)

3) In many different parts of the body (mouth, throat, heart, eye, etc.), birth defects occur which consist of failures or incompleteness of epithelia or other sheets of tissue to fuse with each other.

4) Some birth defects result from chemical deficiencies of vitamins or other substances. For example, the frequency of spinal bifida can be reduced by half or even 3/4 if mothers ingest more of the vitamin named folic acid. In many places, low concentrations of folic acid are added to bread. The incidence of spina bifida in the US is now about 1/1500, down from about 1/1000 or even 1/500 in some states (including NC and SC). In China the frequency has been as high as 1/200 (see pp. 77-78 in Sadler's book). Incidentally, modern methods of making bread reduced normal amounts of folic acid; so adding it back is making bread more normal again.

More examples may be discovered in the future: food deficiencies that increase the probability (& frequency) of birth defects. (Please try to invent a method for detecting such phenomena, even at very low frequencies)

5) Many birth defects are caused by certain chemicals. The word "teratogen" means any chemical (or something like radioactivity) that can cause birth defects.
Unfortunately, alcohol causes much damage (fetal alcohol syndrome).
(Incidentally, a world leader in research on fetal alcohol syndrome is Professor Cathy Sulik of the UNC medical school. Your university is good at lots of things in addition to Basketball.

6) Each particular birth defect results (mostly) from chemical or other damage during its own special time (period of sensitivity) after fertilization.

7) Most of these periods of sensitivity are early in development; many are before a woman would know that she was pregnant.
Therefore it won't work just to avoid those chemicals when you know that you are pregnant. They should be avoided whenever there is a possibility of getting pregnant.

Sensitivity to alcohol has been found to continue through the entire period of pregnancy.

8) Any "morphogen" chemical that normal embryos use for cell-cell communication (like retinoic acid, a form of vitamin A) can be expected to be a "teratogen". Large doses of retinoic acid are effective treatments for acne. "Accutane" has resulted in many birth defects.

British researchers in the 1930s discovered that tissue cultured cells will convert from one kind of epithelia to another; more research is needed in this whole area.


conjoined twins in a chicken

The following text is a quote from the Wikipedia article about conjoined twins. Although it is a very good article, and I recommend it, nevertheless it seems to be assuming several widely-believed misunderstandings about embryology, especially about * what causes identical twinning, and ** what is meant by "stem cells". Are they right about the placenta?

QUOTE from Wikipedia: "Two contradicting theories exist to explain the origins of conjoined twins. The older theory is fission, in which the fertilized egg splits partially. The second and more generally accepted theory is fusion, in which a fertilized egg completely separates, but stem cells (which search for similar cells) find like-stem cells on the other twin and fuse the twins together. Conjoined twins share a single common chorion, placenta, and amniotic sac, although these characteristics are not exclusive to conjoined twins as there are some monozygotic but non-conjoined twins that also share these structures in utero.

Another question for class discussion is this: Before you learned about the inner cell mass and the primitive streak, what did you assume about the process of formation of conjoined twins?

Please, can we have a class discussion about this?

Note: Wikipedia is a wonderful organization and we should all give thanks that it exists (not to mention donation$); however it is also a good place to find interesting, plausible, easy-to-make mistakes about science.

Quotes from the Wikipedia article about "Identical Twinning". " Half-identical or semi-identical twins ...are the result...in which the twins inherit exactly the same genes from their mother but different genes from their father. Although examples of half-identical twins have been found, the exact mechanism of their conception is not well-understood, but could theoretically occur in polar body twinning, where sperm cells fertilize both the ovum and the second polar body.

" Do the ovum and the second polar body contain the same combinations of genes?

Why, or why not?

And a quote from the Wikipedia article titled "Polar Body": Can you find any misunderstandings?

" "Polar twins (or "polar body twins"), where two sperm fertilize an ovum, one of the two fertilizing a polar body, or where an ovum splits into identical copies, one containing a polar body, prior to fertilization, allowing it to be fertilized by two different sperm.

" An excellent source of accurate information is Scott Gilbert's "Developmental Biology" textbook which he generously posted on the internet: Here is the part about polar bodies; it is more than you need to know: http://www.ncbi.nlm.nih.gov/books/NBK10008/

Big improvements have been made in prenatal screening for birth defects. For example, spina bifida and other neural tube abnormalities in a developing fetus result in elevated levels of a specific protein in the mother's blood [more information]. The discovery a few years ago that fetal DNA fragments can also be detected in the mother's blood has led to development of a new test for chromosomal abnormalities that is very accurate and eliminates the risk of miscarriages induced by amniocentesis.

For more on this test, see the following link:

http://www.ncbi.nlm.nih.gov/pubmed/23499003 Click on the icon on the right ("Elsevier Full-Text Article") to get the text of the entire paper. This should work from on campus, or by logging in to the UNC system if you're off campus.


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