ABSTRACT
Despite relatively comparable amounts of alcohol ingestion, not all women who drink excessively give birth to children with fetal alcohol effects. The present study evaluated how maternal age affects the outcome of pregnancy in maternal rats of different ages. All dams were nulliparous and were 66, 121 or 156 days at time of treatment. Alcohol was administered at a dose of 3.5 g/kg, twice daily on gestation days 11-21. Alcohol had a greater impact on offspring born to older- and middle-age dams than to younger dams on a number of attributes including neonatal mortality and birth weight.
Subject(s)
Aging , Ethanol/toxicity , Pregnancy, Animal/drug effects , Animals , Animals, Newborn , Birth Weight/drug effects , Body Weight/drug effects , Drinking/drug effects , Eating/drug effects , Female , Gestational Age/drug effects , Litter Size , Pregnancy , Rats , Rats, Inbred StrainsABSTRACT
The alkylating agent acetoxymethyl-methylnitrosamine (DMN-OAc) triggers preferential left-sided paw defects in mice following IP administration on either day 11 or 12 of pregnancy. Predominantly, ectrodactyly and hypoplasia of the left paws were found. In an organ culture system, using limb buds of 11-day-old mouse embryos, differentiation is severely impaired following addition of 2 microM DMN-OAc to the culture medium. Left and right limbs are equally affected. In contrast, when DMN-OAc is administered in vivo to the dams with subsequent culturing of the limb buds, growth and differentiation of the left limb buds is more affected when compared to the right. Furthermore, DNA alkylation experiments were performed: in vitro, following addition of (14C)-DMN-OAc (2.3 microM) to the culture medium, the DNA alkylation rate of the limb bud DNA is determined. In vivo, following IP administration of 10 mg/kg DMN-OAc to the dams on day 11 of pregnancy, the extent of DNA alkylation of whole-embryo DNA is similar. However, the DNA alkylation rate of separately pooled left and right limb buds exhibits a two-fold difference according to the different teratogenic susceptibility. The results obtained with both in vivo and in vitro systems are consistent with the thesis that a certain amount of DNA alkylation in the tissue of the embryos is the initial step of alkylating agent-induced teratogenicity.
Subject(s)
Abnormalities, Drug-Induced/physiopathology , Alkylating Agents/toxicity , Dimethylnitrosamine/analogs & derivatives , Foot Deformities, Congenital , Abnormalities, Drug-Induced/etiology , Animals , Carcinogens/toxicity , Dimethylnitrosamine/toxicity , Female , Fingers/abnormalities , Forelimb , Gestational Age/drug effects , Hindlimb , Methylnitrosourea/toxicity , Mice , PregnancyABSTRACT
Pregnant CD rats were treated subcutaneously with 0, 0.1, 0.33, or 1.0 mg reserpine/kg/day either on Days 12-15 or on Days 16-19 of gestation. Dams were allowed to deliver and litters (4 +/- 1 of each sex) were weighed weekly and held to 21 days of age. Basal ornithine decarboxylase (ODC) activity and neurochemical determinations were made on hearts and brains, respectively, from pups culled from litters on postnatal Day 1, and from two males and two females/litter at 21 days of age. Following both treatment schedules, the high dose of reserpine resulted in maternal weight loss during dosing, increased stillborn pups, reduced pup weight at birth, retarded postnatal growth, and decreased survival to 21 days of age. Basal cardiac ODC activity was reduced to 33% of control levels only on Postnatal Day 1 in both high-dose groups, while absolute heart weight decreased and relative heart weight increased in these pups. Whole-brain concentrations of two neurotransmitter metabolites, 3-4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA), were increased only at Postnatal Day 1 in the high dose group treated on Days 12-15 of gestation. No other changes were found in concentrations of these metabolites or in the transmitters dopamine and serotonin. The only effect found following administration of 0.33 mg/kg reserpine was a reduction in maternal weight gained during both dosing periods. No signs of toxicity were observed following low-dose exposure on either schedule. Most previously reported postnatal functional studies following reserpine exposure have used mid- to late-gestational treatment with 1.0 mg/kg, a dose shown here to result in marked overt maternal and fetal toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
