Perinatal Cannabis Delayed Puberty in F1 Mice but Effects Faded in Later Generations

Cannabis exposure from gestational day 1 to postnatal day 21 did not disrupt pregnancy or nursing in exposed mothers but produced smaller F1 neonatal pups. F1 females showed delayed vaginal opening (puberty marker) and disrupted estrous cyclicity. F2 and F3 females showed only minor effects. All F1-F3 females had normal ovarian and uterine histology, normal estradiol levels, and produced normal offspring.

Pregnant mice exposed to cannabis extract (100 or 200 mg/ml THC) from gestational day 1 to postnatal day 21 (twice daily). F1, F2, and F3 female offspring assessed for puberty onset (vaginal opening), estrous cyclicity, ovarian/uterine histology, plasma estradiol, and fertility outcomes.

Cannabis use during pregnancy is increasing, and concerns about multigenerational effects are largely untested. This study provides reassuring evidence that while first-generation offspring show some reproductive disruption, the effects attenuate in subsequent generations and do not compromise actual fertility.

Transgenerational effects of drug exposure are a growing concern in reproductive toxicology. This study suggests cannabis's reproductive effects are primarily developmental (affecting the exposed generation) rather than truly transgenerational (persisting in unexposed generations), which is a relatively favorable finding compared to some environmental exposures.

Mouse model with cannabis extract delivered by inhalation may not replicate human dosing. Only female reproductive outcomes studied. Behavioral and cognitive outcomes in offspring not assessed. THC concentrations in cannabis extract may not reflect human products. Estrous cycle disruption could have functional consequences not captured by fertility endpoints alone.