Effects Of Prenatal Ethanol Research Articles

Suppression of Immune Responsiveness: Sex Differences in Prenatal Ethanol Effects

Exposure to ethanol in utero results in changes in the offspring's developing immune system, including thymus lymphocyte subpopulation shifts and functional lymphocyte changes that persist in adult animals. The present study was designed to define further the extent of changes in the immune system that result from fetal ethanol exposure and to compare effects in male and female offspring. In adulthood, male and female offspring from Sprague-Dawley dams fed an ethanol-containing liquid diet (alcohol, A), an isocaloric liquid control diet (pair-fed, PF), or laboratory chow and water (control, C) during pregnancy were tested for several measures of immune competency. Prenatal ethanol exposure differentially affected male and female offspring. Fetal ethanol-exposed males exhibited a decrease in thymocyte number as well as a decreased splenic lymphocyte proliferative response to the T-cell mitogen, concanavalin A (Con A), with a concomitant decrease in recoverable blast cells, when compared with PF and C males. Further, the defect in T-cell proliferation of A males was not due to an inability to produce the critical growth factor, interleukin-2 (IL-2), but to an inability of lymphoblasts to utilize exogenous IL-2. Fetal ethanol-exposed females showed some suggestion of lower thymocyte counts and decreased splenic T-cell proliferative responses to Con A compared to PF and C females. For most of the immune measures, however, no significant differences occurred among A, PF, and C females. In utero ethanol exposure did not significantly alter spleen cell counts or IL-2 production, splenic B-cell proliferation to bacterial lipopolysaccharide (LPS), or thymocyte response to IL-2 in animals of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Prenatal Ethanol and Long‐Chain n‐3 Fatty Acid Supplementation on Development in Mice. 2. Fatty Acid Composition of Brain Membrane Phospholipids

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. The diet also contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Birth occurred on day 19, and the fatty acid composition of the brain membrane phospholipids was determined in the pups 3 days after birth (day 22 postconception) and again, 10 days later (day 32 postconception). On day 22 the polyunsaturated fatty acid (PUFA) composition of the brain phospholipids reflected dietary availability, with the n-3/n-6 ratio higher in the n-3 groups; this was decreased by ethanol in the phosphatidylcholine (PC) fraction. The dietary effect was still apparent on day 32; again ethanol reduced this in both the PC and phosphatidylethanolamine (PE) fractions. The n-3 oil, but not ethanol, increased the 20:3n-6/20:4n-6 ratio, indicative of an inhibition of the activity of delta-5 desaturase. With respect to the 22:C compounds, the n-3 oil decreased the levels of 22:5n-6, while increasing those of 22:6n-3, but generally the sum of these two fatty acids remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Prenatal Ethanol and Long‐Chain n‐3 Fatty Acid Supplementation on Development in Mice. 1. Body and Brain Growth, Sensorimotor Development, and Water T‐Maze Reversal Learning

Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. In addition, the diet contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Ethanol decreased maternal weight gain and pup body and brain weight; it also retarded both sensory and motor development in the pups and impeded reversal learning in a water maze. The n-3 supplementation lowered maternal blood alcohol concentration, but counteracted only some of the effects of ethanol, by increasing maternal weight gain and pup body weight, and also by enhancing sensory development in the pups. Such effects were additive, in that they were also present in the maltose-dextrin control group. These findings suggest that n-3 supplementation may ameliorate some of the effects of ethanol on neurobehavioral development, but the magnitude of the effect appears to be small.

Interactive effects of prenatal ethanol and N-3 fatty acid supplementation on brain development in mice.

This study assesses the combined effects on brain and behavioral development of ethanol administration and supplementation of the maternal diet with long chain n-3 polyunsaturated fatty acids. From day 7 to 17 of gestation, pregnant mice were fed equivalent daily amounts of isocaloric liquid diets; 20% of the energy was provided by either ethanol or maltose-dextrin, and a further 20% by either safflower oil (rich in linoleic acid, 18:2 n-6), or a combination of safflower oil with a fish oil concentrate (rich in eicosapentaenoic acid, 20:5 n-3, and docosahexaenoic acid, 22:6 n-3). On day 18 the liquid diets were replaced by lab chow; a fifth group was maintained on lab chow throughout the experiment. Measures on the pups included brain weight and the fatty acid composition of the brain phospholipids on days 22 and 32 post-conception (birth = day 19), as well as behavioral development. Maternal weight gain during gestation was decreased by ethanol relative to maltose-dextrin, and increased by fish relative to safflower oil. On day 32, the brain weight of ethanol-treated animals fed fish oil was greater than their safflower oil controls, whereas the reverse was true in the two maltose-dextrin groups; a similar trend was apparent on day 22. The brain phospholipid content of the longer chain fatty acids (20:4 n-6, 22:4 n-6, 22:5 n-6, 20:5 n-3, 22:5 n-3, 22:6 n-3) on day 22 reflected that of the prenatal diet, with the proportion of n-3 compounds being higher and that of n-6 lower in the fish oil than safflower oil groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal Ethanol Exposure Alters Adrenocortical Development of Offspring

Interactive effects of prenatal ethanol and maternal nutritional status on reproductive outcome and maternal and offspring adrenocortical activity were examined. Ethanol was administered to pregnant females in liquid diets (36% ethanol-derived calories) which were marginal or optimal in terms of requirements for pregnancy. Both pair-fed and ad libitum fed control groups were included. Females consuming ethanol from gestation Day 1 through parturition gained less weight, were delayed in parturition, and had fewer and smaller live born young than pair-fed or control females, regardless of whether they consumed marginal or optimal diets. Withdrawing ethanol on Day 21 of gestation attenuated many of ethanol's adverse effects on reproductive outcome. However, prenatal maternal ethanol intake altered adrenocortical activity/responsiveness of the mother, the fetus, and the preweaning offspring, regardless of maternal nutritional status. Relative adrenal weights and basal corticosterone levels were increased in the dam both prenatally and at parturition. Ethanol-exposed fetuses (A) had increased relative adrenal weights but lower basal corticosterone levels than pair-fed (PF) and control (C) fetuses on gestation Day 21. At birth, plasma and adrenal corticosterone levels were increased, while absolute adrenal weights and corticosterone binding globulin (CBG) binding capacity were decreased in A neonates. At 5 days of age, A pups showed reduced plasma corticoid responses to ether at 15 min poststress and to novelty or saline injection at 90-min post stress compared to PF and C pups. CBG binding capacity was also reduced in A pups. At 10 days of age, plasma corticosterone levels were lower overall in A and PF than in C pups following exposure to a number of different acute stressors while at 18 days plasma corticoids were decreased and adrenal corticosterone was increased in A compared to PF and/or C pups. These data support and extend previous studies indicating that in utero ethanol exposure alters postnatal adrenocortical development. This effect is specific to ethanol and unaltered by maternal nutritional status.

Hyperresponsiveness to stress: differential effects of prenatal ethanol on males and females.

In this study we investigated the hypothesis that pituitary-adrenal response inhibition is compromised in animals prenatally exposed to ethanol. In the first experiment, we examined whether opportunity to perform a consummatory response reduces the adrenocortical response to a novel test cage. Animals were water deprived for 24 hr and tested in one of three conditions: (a) removed from home cage, blood sample obtained immediately; (b) placed into empty novel cage, blood sample obtained 30 min later; (c) placed into novel cage with water available, blood sample obtained 30 min later. All animals showed an increase in corticoids over basal levels following 24-hr water deprivation, and placement into a novel cage produced a further significant increase in corticosterone. Opportunity to drink reduced the corticosterone response to novelty for all males. However, fetal ethanol-exposed females showed significantly less attenuation of their corticosterone response to novelty than both pair-fed and control females. In the second experiment, we examined adrenocortical habituation to a stressful stimulus. Animals were restrained in plastic tubes which restricted movement, and blood samples were obtained following 30 or 60 min of restraint. All animals showed significant corticoid elevations at 30 min. Males showed no change in corticoids from 30 to 60 min while both pair-fed and control females showed a corticoid decrease at 60 min. Fetal ethanol-exposed females, however, showed no significant corticoid decrease at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal ethanol weakens the efficacy of reinforcers for adult mice.

Pregnant C57BL/6cr mice were fed a liquid diet containing 20% of the total calories from either ethanol (E) or sucrose (S) for gestation days 5-17. Adult male and female (six of each from both prenatal-treatment groups) offspring were tested under various schedules of food reinforcement. The first phase was a test of fixed-ratio (FR) acquisition in which the required number of responses per unit of reinforcement was increased from 1 to 20 to 100. Prenatal ethanol exposure interacted with other factors to produce an acquisition deficit. The second phase involved responding under extinction (Ext). Under standard Ext procedures there were no prenatal-ethanol effects; however, when a conditioned reinforcer was superimposed on an FR 5, the E males did not increase their rates as much as the S males. Finally, under a multiple FR 5 DRO 15-sec (differential-reinforcement-of-other-behavior) arrangement, prenatal-ethanol effects were found in each component. For the FR 5 component, prenatal ethanol eliminated the sex differences found in the S subjects. For the DRO 15-sec component, prenatal ethanol elevated response rates. The results indicate a general decreased efficacy of positive reinforcement in adult mice following prenatal ethanol exposure.

EFFECT OF PRENATAL EXPOSURE TO ETHANOL ON ADULT ETHANOL PREFERENCE AND RESPONSE TO ZIMELIDINE IN RATS

The effects of prenatal ethanol (ETOH) exposure (2.8-3.5 g/kg per day) on subsequent adult ETOH preference and on ETOH consumption after treatment with zimelidine, a serotonin uptake inhibitor, were investigated. Pregnant rats were exposed to an ETOH/saccharin solution in the first, second, third, all three, or none, of the trimesters of the gestation period. As adults, the offspring were subjected to a 40-day screening procedure to determine ETOH preference (greater than 50% of total daily fluid consumption) over water (experiment 1). Only animals which preferred ETOH were included in experiment 2, in which they received either five daily injections of zimelidine (20 mg/kg) or comparable volumes of Ringer's solution. Results indicated that although there were no differences between groups in terms of ETOH preference, a significant difference was evident in ETOH intake after zimelidine treatment. All groups of rats showed a significant decrease in ETOH intake from baseline levels when given zimelidine. However, only rats prenatally exposed to ETOH in the first trimester demonstrated a significant decrease in ETOH drinking when compared to controls. These results suggest that early prenatal ETOH exposure, even in moderate doses, may induce central neurochemical alterations that are salient enough to be detected in adulthood.

The effects of prenatal ethanol in cynomolgus monkeys.

Ethanol was administered to pregnant cynomolgus monkeys (Macaca fasicularis) from day 20 to 150 of gestation. The ethanol was delivered by intragastric intubation twice a day at 8 AM and 5 PM. Dosage was begun at a relatively low level, 2 g/kg/day and increased gradually to attain a final dosage of 4 or 5 g/kg/day. The offspring were allowed to be delivered naturally and remained with their mother until 23 days of age when they were sacrificed. Maternal blood ethanol and acetaldehyde levels were monitored at weekly intervals throughout pregnancy. Pregnancy wastage in the form of abortions and stillbirths was increased by ethanol treatment especially at the high dose. Birthweight was significantly lowered in offspring of mothers receiving 5 g/kg/day of ethanol. However, no structural malformations or facial changes suggestive of those seen in the human fetal alcohol syndrome were found in any of the offspring. We conclude that the conditions of our study did not produce a satisfactory model of human fetal alcohol syndrome.

Prenatal ethanol effects on developing neuroendocrine systems

Prenatal ethanol effects on developing neuroendocrine systems

Behavioral effects of prenatal ethanol exposure and differential early experience in rats

Offspring of rats that were intubated with ethanol during Days 10–14 of gestation and offspring in two control groups were compared on measures of growth, viability, and performance in behavioral tasks. Influences of postnatal environment were assessed by using fostering-cross fostering procedures and by providing different postweaning housing conditions. Results were that offspring from dams treated with ethanol displayed prenatal and postnatal growth deficiency as well as increased postnatal mortality. In the open field, offspring in the Ethanol group were more active than those in the other two groups. Ethanol offspring were also more active in the Y maze and made more avoidance responses and correct discriminations. Early experience as manipulated by the fostering-cross fostering procedures and post-weaning rearing conditions had no impact on the effects of prenatal ethanol on offspring growth, viability, or behavior.