A new study led by UCSF researchers that examines the role of oxygen in the development of the placenta may be key in bringing scientists closer to understanding the causes of preeclampsia -- a life-threatening complication of pregnacy.

The condition is characterized by slowed growth of the fetus as well as maternal high blood pressure and kidney disease in pregnancy.

The study was conducted by scientists at UCSF and the University of Rochester in New York. Researchers, led by chief investigator Susan Fisher PhD, UCSF professor of stomatology and obstetrics, gynecology and reproductive sciences, examined cultured cells from the placenta in contrasting environments of two per cent oxygen and 20 percent oxygen.

The scientists found that the higher oxygen level caused placental cells to stop multiplying and to differentiate into the invasive tumor-like cells needed to sustain a healthy pregnancy. These cells invade the uterus to connect the placenta to the mother and to establish blood flow, Fisher said.

The scientists also found that the two percent oxygen level caused the cells to continue to multiply and their ability to differentiate into the necessary tumor-like cells was impaired. When this happens in the uterus, the placenta fails to obtain an adequate supply of maternal blood and pregnancy diseases such as preeclampsia may follow, researchers said.

In the early stages of pregnancy, the embryo develops in a two per cent oxygen atmosphere that favors multiplication of placental cells. This unusually low oxygen level enables the placenta to develop quickly so that attachment of the early embryo to the uterine wall is possible. (A study by Fisher earlier this year described how that process goes awry in preeclampsia.) But if this low oxygen level continues for too long, placental cells cannot adequately differentiate and their tumor-like progression into the uterus is impaired. As a result, the attachment between the fetus and the mother remains tenuous, which can predispose a woman to serious pregnancy complications.

The new study, which appears in the Sept. 12 issue of Science, will "help to clarify the origins of preeclampsia -- the first step in developing methods of predicting and treating this disorder," says Fisher.

About 7 percent of first-time mothers and 1 to 2 percent of mothers having subsequent pregnancies develop preeclampsia. Increased risk has been associated with teenage mothers, mothers over 40 and African American women, according to experts. The condition occurs suddenly without warning and sometimes in as little as a few hours. Usually, a pregnant women with preeclampsia develops dangerously high blood pressure and begins secreting protein in the urine. In some cases, the condition may progress to eclampsia, a series of potentially fatal seizures. Preeclampsia is still one of the leading causes of maternal mortality. The need to screen and detect the condition early was one of the original reasons the medical community many years ago began recommending regular prenatal visits.

Although the high blood pressures accompanying preeclampsia can be treated with drugs, the only effective treatment for the condition is immediate delivery of the baby.

Co-authors of the study are: Olga Genbacev, PhD, UCSF department of stomatology; Yan Zhou MD, UCSF department of stomatology; John Ludlow, PhD, University of Rochester, department of biochemistry and biophysics.

By Suzanne Leigh

1st appeared 9/15/97