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

The takeaway

Cannabis exposure during pregnancy and nursing delayed puberty and disrupted estrous cycles in first-generation female mice, but these reproductive effects were minor in second and third generations and did not compromise fertility.

Reproductive toxicologists, obstetricians, and researchers studying developmental effects of prenatal cannabis exposure.

What the researchers found

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.

Why it matters

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.

The numbers in context

THC in cannabis extract: 100 and 200 mg/ml. Exposure: gestational day 1 to postnatal day 21 (twice daily). F1 pups were smaller. F1 females: delayed vaginal opening, disrupted estrous cycles. F2 and F3: minor effects only. All generations: normal ovarian/uterine histology, normal estradiol, normal fertility.

How the study worked

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.

What this study cannot tell us

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.

How to read the evidence

Multigenerational design with comprehensive reproductive endpoints, but mouse model and cannabis extract delivery method limit human translation.

When this study was published

Published 2025.

The bigger picture

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.

Questions still open

Whether male reproductive parameters show similar transgenerational patterns
Whether the puberty delay in F1 females has implications for bone density, metabolic health, or other puberty-sensitive outcomes

Common questions

Could cannabis during pregnancy affect my grandchildren?

This mouse study suggests the effects are mostly limited to the directly exposed generation (F1). Second and third-generation females showed only minor changes and had normal fertility. However, mouse results should be interpreted cautiously when applying to human pregnancy.

Did the cannabis harm the mothers?

No. Pregnancy and nursing were not disrupted in the exposed mothers, and gestational length, litter size, and sex ratios were normal. The main finding was smaller neonatal pups and later reproductive timing changes in the female offspring.

Read the original research

Transgenerational effects of perinatal cannabis exposure on female reproductive parameters in mice.

Toxicological sciences : an official journal of the Society of Toxicology, 205(2), 358-368

View on PubMed ↗Publisher’s paper ↗

Citation

Shi, Mingxin; Oh, Yeongseok; Mitchell, Debra A; MacLean, James A; McLaughlin, Ryan J; Hayashi, Kanako. (2025). Transgenerational effects of perinatal cannabis exposure on female reproductive parameters in mice.. Toxicological sciences : an official journal of the Society of Toxicology, 205(2), 358-368. https://doi.org/10.1093/toxsci/kfaf043