Hypotensive episodes are frequent during pregnancy, and their functional effect on fetal brain has not been studied. We produced systemic hypotension for 30 min during mid-gestation in pregnant rats and examined their offspring on postnatal days 1 and 28. When compared with sham controls, the brain of the hypotensive group contained more TUNEL-positive cells in the hippocampal and periventricular regions on both time points. Spatial learning assessed by water milk maze test was impaired in 28-day-old pups of the hypotensive mothers. According to these results, transient maternal hypotension can induce apoptotic cell death in fetal brain and affect learning. Similar mechanisms may be considered and investigated in the pathogenesis of human learning disorders. Maternal, fetal, or placental factors that diminish uteroplacental and fetal circulation are associated with an increased incidence of fetal CNS malformations (1-3). While marked intrauterine perfusion failure might be related to major malformations, less severe or shorter hypoperfusion may take part in the pathogenesis of minor or functional cerebral disturbances. A frequent cause of hypoperfusion in pregnant women is hypotension: uteroplacental blood flow is known to diminish at blood pressures below 110/65 mm Hg. Hypotension may occur spontaneously, but is most frequently induced by position or drug treatment (4 -6). Orthostatic hypotension in late pregnancy was found to be associated with low birth weight (7,8). Although hypotension is considered potentially harmful for the fetus, its symptoms may be unnoticed or disregarded in pregnancy, and little clinical evidence exists on the effects of moderate and transient hypotension. In our previous experiments simulating hypotensive episodes encountered in pregnant women, we reported that transient maternal hypotension increased apoptotic cell death in the fetal brain (9). In the current study, we investigated the effect of intrauterine hypotensive episodes on cognitive functions in addition to morphologic features.
METHODS
Gestational hypotension.Ten 3-mo-old pregnant Wistar rats were included in the study: on the 15th day of pregnancy, five were subjected to transient hypotension by femoral artery catheterization (hypotension group) and five underwent all procedures except hypotension (control group) as described before (9). According to preliminary experiments this was associated with an average 46% reduction in uterine blood flow. Briefly, rats were anesthetized following an overnight fasting by intraperitoneal 30 mg/kg ketamine (Ketalar®, Eczacibasi, Istanbul) and 8 mg/kg xylazine (Rompun®, Bayer, Istanbul), the left femoral artery was catheterized, blood pressure (BP) was recorded using a pressure transducer (Transbridge W P I, Sarasota, FL, U.S.A.) and data were sent to computer via MacLab 4/s data acquisition unit (AD instruments, Castle Hill, Australia). Heart rate (HR) and mean BP
