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Review
43.3 Cell movements during gastrulation result in three germ layers and new tissue interactions.
43.3 Inductive tissue interactions can suppress as well as activate.
43.4 Segmented blocks of cells, known as somites, produce cells that develop into the vertebrae, ribs, trunk muscles, and limbs.
43.4 Genetic and environmental factors can lead to neural tube defects.
43.5 During the first trimester, the embryo is most sensitive to environmental effects.
Original Paper: Finnell, R. H., J. D. Waes, J. D. Eudy and T. H. Rosenquist. 2002. Molecular basis of environmentally induced birth defects. Annual Review of Pharmacology and Toxicology 42: 181–
Both genetic and environmental factors—
Questions
An infant has various bone, cardiovascular, and muscular system defects. Is this consistent with a vitamin A deficiency? Explain your answer.
No, the symptoms are not consistent with vitamin A deficiency. The baby’s defects are in mesenchyme tissues. A deficiency of vitamin A would most likely lead to defects of tissues derived from the ectoderm. In fact, the defects exhibited are consistent with an excess of vitamin A.
Suggest a reasonable hypothesis for why vitamin A has different effects on ectoderm-
The ectoderm and the mesoderm express different genes. This results in mesoderm-
Suppose there is a genetic variant that causes faster progression through G1 phase of the cell cycle. Would you expect individuals with this variant to be more susceptible or less susceptible to valproic acid during early development?
Individuals with this variant may be expected to be less susceptible to valproic acid. Because the variant enhances progression through G1 phase, the effect of valproic acid impeding this progression should be mitigated.
A woman takes valproic acid before she realizes she is pregnant. Would supplements of folic acid be beneficial for this woman’s pregnancy? Explain your answer. Why would effects of valproic acid occur so early in the pregnancy?
Even for women who have not been exposed to valproic acid, supplements of folic acid have been shown to reduce the frequency of neural tube defects. Given that valproic acid exposure increases risk for these defects, additional supplements of folic acid may counteract the effect of valproic acid. The extent to which additional folic acid could help would depend in part on whether and how these chemicals are involved in the same developmental processes. Valproic acid may have effects early in pregnancy—
Folate receptor alpha is a protein that is involved in bringing the biologically active form of folic acid into cells. Explain how variants of this protein could affect the frequency of neural tube defects during pregnancy.
Because deficiencies of folic acid increase the risk of neural tube defects, the efficiency of the receptor should affect this risk. Individuals who have receptor proteins that are more efficient in bringing folic acid to the cell should have greater cellular availability of folic acid and thus be at lower risk for neural tube defects compared with individuals who have less efficient receptor proteins.
| Chemical/ agent |
Effects on fetus | Comments |
|---|---|---|
| Folic acid | Deficiency increases the risk of neural tube defects. | Genetic variants at folate receptor alpha affect the risk of neural tube defects. |
| Vitamin A | Excess increases mesenchyme defects. Deficiency increases ectoderm defects. | Vitamin A is not synthetized by humans; it must be acquired from the diet. |
| Valproic acid | Exposure increases the risk of neural tube and other neural defects, craniofacial abnormalities, and skeletal defects. | Valproic acid is used to treat bipolar disorder and epilepsy. It appears to act by impeding the cell cycle during G1 phase. |
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