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Pre- and post-conceptional tobacco effects on the CD-1 mouse fetus
R B Paulson1, J Shanfeld, L Prause
1Department of Oral Biology, College of Dentistry, Ohio State University, Columbus 43210.
Abstract:
The objective of this study was to examine the effect of subchronic administration of an aqueous extract of smokeless tobacco (ST) on the development of the CD-1 mouse fetus. Mice were administered ST for approximately 5 weeks: for 2 weeks prior to breeding, during breeding, and during gestational days 0 to 17. Thus the initial peak nicotine levels occurred prior to breeding and not during the critical periods of gestation. Two ST dosages were administered by gastric intubation three times daily: ST/D-1, equivalent to a dose of 12 mg nicotine/kg of body weight, and ST/D-2, equivalent to 20 mg nicotine/kg body weight. Maternal plasma nicotine levels were determined 30 min after the second intubation during the pretreatment and gestational phases of treatment. At these ST dosages, the weight gain of ST-treated dams was not significantly affected in comparison to treated controls. The mean maternal plasma nicotine level for the low-dosage group was 363 ng/ml, and 481 ng/ml for the high-dosage group, with maternal lethality observed at 9.6% and 28.2%, respectively. No significant differences were seen between control and ST/D-1 maternal and/or fetal values, except for placental weights which were heaviest in the ST group (P less than 0.05). Several differences were noted between the ST/D-2 group and controls: fetal weights were reduced by 5.4% (P less than 0.05); decreased ossification was seen in femur measurements and in nine of ten characteristics measured (P less than 0.05); the frequency of resorptions (7.6%) was almost doubled (controls 4.2%); and the frequency of deaths and malformations was not affected. Under these experimental conditions, the low dose produced a negligible effect on the CD-1 mouse fetus and the dam. The high dose demonstrated growth retardation (P less than 0.05), increased embryotoxicity, and a significant decrease in ossification (P less than 0.05).
Insights
Subchronic smokeless tobacco (ST) exposure during mouse gestation impacted fetal development. High-dose ST caused fetal growth retardation, increased embryotoxicity, and reduced ossification, while low-dose ST had minimal effects.
Area of Science:
- Toxicology
- Developmental Biology
- Reproductive Science
Background:
- Smokeless tobacco (ST) use is prevalent, and its effects on fetal development require thorough investigation.
- Understanding the impact of nicotine exposure from ST during critical gestational periods is crucial for public health.
- Previous research has not fully elucidated the specific effects of subchronic ST administration on mammalian fetal development.
Purpose of the Study:
- To evaluate the effects of subchronic smokeless tobacco (ST) aqueous extract administration on CD-1 mouse fetal development.
- To assess dose-dependent impacts of nicotine exposure from ST on maternal and fetal parameters during gestation.
Main Methods:
- Mice received ST extract (low dose: 12 mg nicotine/kg; high dose: 20 mg nicotine/kg) via gastric intubation for 5 weeks, including pre-breeding and gestation (days 0-17).
- Maternal plasma nicotine levels were measured, and maternal weight gain, fetal parameters (weight, ossification, resorptions, malformations), and placental weights were analyzed.
- Control groups received no ST extract.
Main Results:
- Low-dose ST (ST/D-1) showed negligible effects on maternal and fetal outcomes, except for increased placental weight.
- High-dose ST (ST/D-2) resulted in significantly reduced fetal weight (5.4%), decreased ossification, nearly doubled resorption frequency (7.6% vs. 4.2%), and maternal lethality (28.2%).
- Maternal weight gain was not significantly affected by either ST dose.
Conclusions:
- Subchronic exposure to a low dose of smokeless tobacco extract had minimal adverse effects on CD-1 mouse dams and fetuses.
- A high dose of smokeless tobacco extract during gestation induced significant fetal growth retardation, embryotoxicity, and impaired ossification.
- These findings highlight the dose-dependent risks of smokeless tobacco consumption during pregnancy, particularly concerning developmental toxicity.