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Drug Abuse During Pregnancy Inhibit Ability Of Placenta Cells To Uptake Folate

A study using human placental cells may help explain how drugs of abuse used during pregnancy - including alcohol, nicotine, ecstasy, amphetamine and hashish - can produce toxic effects on the developing fetus.  

In a paper presented on April 29 at Experimental Biology 2007, in Washington, DC, researchers from the Department of Biochemistry of the Medical Faculty in Porto University and the Department of Gynecology and Obstetrics in S. Joao Hospital in Porto, Portugal, reported that these substances, sometimes at doses below “recreational” blood level, inhibited uptake of folates by cells taken from human placenta. The presentation is part of the scientific program of The American Physiological Society.

Folates such as folic acid play an essential role in the synthesis of DNA and RNA and, for this reason, they become particularly important for normal fetal development and growth.  Inadequate folic acid during early stages of fetal development increases the risk of neural-tube defects such as anencephaly and spinal bifida. This is why pregnant women take folic acid supplements and why many countries supplement bread and other common foods since it is also important that women have adequate folate levels before they conceive.

The fetus obtains folic acid exclusively from the maternal blood, through placental transport. The placenta has several functions, including transporting nutrients and oxygen from the mothers' circulation to that of the fetus, eliminating waste metabolites from fetal blood, synthesizing hormones and peptides that support placental development and sustain pregnancy, and functioning as a barrier to protect the fetus against the mother’s immune system.  In order to do this, the placenta must be permeable to nutrients and oxygen - but it also is permeable to foreign compounds such as the drugs listed above.

Elisa Keating, a doctoral student in the laboratory of Dr. Fatima Martel, examined the effect of acute (26 minutes) and chronic (48 hours) exposure of cultured human placental cytotrophoblasts to common drugs of abuse and also to high serotonin and glucose levels, found in the blood of mothers with preeclampsia and diabetes respectively; anti-hypertensive drugs such as clonidine, atenolol, alpha-methyldopa and labetalol; and insulin, used in the treatment of the mother’s diabetes. 

The good news was that both chronic and acute exposure of the cells to insulin, serotonin, and the majority of the prescription drugs did not seem to impair the transport of the folates into the placental cells.  However, the drugs of abuse did inhibit the vitamin uptake, as did the acute labetalol and chronic atenolol. 

Ms. Keating and Dr. Martel say that while the results must be confirmed in in vivo studies, they do suggest that inhibition of placental uptake of folates may be one of the mechanisms involved in these drugs’ known toxicity to the fetus.

The work was supported by FCT and Programa Ciencia, Tecnologia e Inovacao do Quadro Comunitario de Apoio.

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,500 members and publishes 15 peer-reviewed journals with a worldwide readership.