Teratogenic effects of hyperthermia in the bonnet monkey (Macaca radiata)

Abstract

Seventeen timed-mated bonnet monkeys fMacaca radiata) were exposed to hyperthermia in a forced-draft incubator for a duration of one, three, four or eight days between 21 and 46 days of gestation. On each day of exposure the core temperature of the pregnant animal was elevated 2.4 to 5.4OC above the reference temperature recorded before heat exposure. Malformations occurred following a one-hour daily elevation of the core temperature above the reference temperature under the following exposure conditions: 3.BoC, days 23 to 26; 3.9"C, days 24 to 27; 2.4"C, days 27, 28 and 30; and 4.1°C, day 26 of gestation. Five resorptions occurred following exposure for one, three or four days between days 24 and 29 of gestation after core temperature elevation of 3.7 to 4.4"C and three abortions occurred following exposure for four days between days 24 and 35 of gestation after core temperature elevation of 2.6 to 3.9OC. The results clearly indicate that the teratogenic sensitive period is from 23 to 30 days gestation following elevations of the core temperature from 2.4 to 4.1"C. No distinct pattern of malformations was observed although skeletal and umbilical cord malformations were the most common. Pathological changes in placental structure, expecially maternal surface infarctions and intervillous thrombi, were associated with three of the four abnormal fetuses, suggesting a relationship between pathological placental characteristics and fetal malformations in this study. The degree of core temperature elevation which resulted in malformations in the present study are similar to those applied to other mammalian species, and the specific anomalies observed in the bonnet monkey resemble those observed in other mammalian species, including man.

Effects of Prenatal Heat Stress on Postnatal Growth, Behavior and Learning Capacity in Mice

“…Thus, it seems likely that postnatal behavior and learning capac ity of prenatally heated mice are correlated more closely with their brain weights than with their body weights. The retardation of brain development following maternal heat ing have been reported also in rats [22,23], rabbits [24], and bonnet monkeys [25], Ed wards [26] examined the relationship be tween the body and brain growth of prena tally heated guinea pigs and found that the retardation was more specific for brain de velopment than for general body growth, which contrasts with the effects of undernu trition that produces a greater deficit in gen eral body growth than in brain growth.…”

Seasonal Variation in Pre-Eclamptic Rate and Its Association with the Ambient Temperature and Humidity in Early Pregnancy

“…Intracellular damage, inhibition of mitosis and cellular migration, and cell death may occur after heat exposure [19] . Other mechanisms of cell injury due to heat may involve microvascular lesions [20] , placental necrosis [21] , and infarction [22] . Milunsky et al [23] report that maternal heat exposure in the first trimester of human pregnancy was associated with an increased risk for neural tube defects.…”

Induction of Neural Tube Defects and Skeletal Malformations in Mice following Brief Hyperthermia in utero

“…One of the main targets of heat is the developing neural tis sue and therefore mouse embryos are highly susceptible to hyperthermia around the time of neural tube closure. NTDs have been pro duced by heating pregnant animals in other strains of mice [Webster and Edwards, 1984;Finnel et al, 1986], rats [Skreb and Frank, 1963;Edwards, 1968;Germain et al, 1985] , hamsters [Kilham and Ferm, 1976;Umpierre and Dukelow, 1977] and nonhu man primates [Hendrickx et al, 1979], It has been shown that the susceptibility to heat-induced NTDs varies considerably among various strains of mice, suggesting that the sensitivity of the embryo to hyper thermia may be genetically determined [Webster and Edwards, 1984;Finnel et al, 1986] , In the present study, a single heating as brief as 7.5 min at 43.0 °C produced a signif icant number of NTD embryos. A single heating at 42.0 °C was also teratogenic if it is applied for a sufficient duration, i.e.…”

“…Studies with experimental animals have shown that heat can produce malformations in the rat [Skreb and Frank, 1963;Edwards, 1968;Germain et al, 1985], mouse [Webster and Edwards, 1984;Finnel et al, 1986], hamster [Kilham and Ferm, 1976;Umpierre and Dukelow, 1977], guinea pig [Edwards, 1969a, b;Edwards et al, 1974Edwards et al, , 1984, and nonhuman primate [Hendrickx et al, 1979]. In these animal species, the developing cen tral nervous system, especially the brain, has been most commonly affected.…”