Paternal nicotine exposure in rats produces long-lasting neurobehavioral effects in the offspring

Abstract

Studies of intergenerational effects of parental chemical exposure have principally focused on maternal exposure, particularly for studies of adverse neurobehavioral consequences on the offspring. Maternal nicotine exposure has long been known to cause adverse neurobehavioral effects on the offspring. However, paternal toxicant exposure has also been found to cause neurobehavioral toxicity in their offspring. Recent work suggests that paternal nicotine exposure can have epigenetic effects, although it remains unclear whether such changes lead to neurobehavioral effects. In the current study, we investigated the effects of paternal nicotine exposure on neurobehavioral development of their offspring. Male Sprague-Dawley rats were exposed to 0 or 2 mg/kg/day nicotine (sc) for 56 consecutive days with two consecutive 2ML4 osmotic minipumps. Following treatment, these males were mated with drug-naïve female rats. Offspring of both sexes were tested in a behavioral battery to assess locomotion, emotional function and cognition. Paternal nicotine exposure did not impact offspring viability, health or growth. However, behavioral function of the offspring was significantly altered by paternal nicotine exposure. Male offspring with paternal nicotine exposure exhibited locomotor hyperactivity in the Figure-8 apparatus when tested during adolescence. When retested in adulthood and regardless of sex, offspring of the nicotine exposed father showed significantly

Sperm DNA methylation altered by THC and nicotine: Vulnerability of neurodevelopmental genes with bivalent chromatin

“…While we were able to characterize these changes in the sperm of exposed rats, we have not yet examined potential heritability of these changes. Initial studies have demonstrated behavioral effects as the result of paternal exposure to nicotine 67 and THC 68 . It will be important to examine offspring brain DNA methylation and relationship to behavioral effects.…”

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols

“…Similarly, dams were exposed only to e-cigarette aerosol after the presence of a seminal plug, with no exposures occurring prior to the start of pregnancy. A previous study in rats noted a developmental impact on offspring following daily paternal nicotine injections (2 mg=kg) to the males prior to the start of breeding (Hawkey et al 2019). Therefore, e-cigarette aerosols with and without nicotine may have additive or synergistic effects when exposure occurs prior to pregnancy and during the gestational period and when both biological parents are exposed.…”

NRF2 loss recapitulates heritable impacts of paternal cigarette smoke exposure

“…We next sought to determine whether paternal CS exposure had any effect on offspring phenotype. Given that brain and nervous systems were previously reported to be sensitive to preconception paternal exposures [25][26][27][28], we investigated DNAme by RRBS in the prefrontal cortex of F1 mice derived from CS-exposed sires compared to the offspring of unexposed males (n = 8 per group). These experiments were performed exclusively on male mice in order to avoid confounding due to sex-related differences in DNA methylation and RNA expression.…”

“…The findings reported here may also be useful in understanding the risks of other environmental exposures that induce oxidative stress such as air pollution and some chemical exposures. Paternal preconception exposures to a variety of pharmacologic agents and pollutants, including nicotine, THC, morphine, and benzo[a]pyrene affect offspring phenotype, and often confer neurobehavioral consequences [25][26][27][28][51][52][53][54]. In some cases, the impacts are transmitted across multiple generations [52,53].…”