Recent reports indicate that 7% of pregnant mothers in North America use cannabis. This is concerning given that in utero exposure to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive component in cannabis, causes fetal growth restriction and may alter replication and survival of pancreatic β-cells in the offspring. Accordingly, we hypothesized that maternal exposure to Δ9-THC during pregnancy would impair postnatal glucometabolic health of offspring. To test this hypothesis, pregnant Wistar rats were treated with daily intraperitoneal injections of either 3 mg/kg Δ9-THC or vehicle from gestational day 6 to birth. Offspring were subsequently challenged with glucose and insulin at 5 months of age to assess glucose tolerance and peripheral muscle insulin sensitivity. Female offspring exposed to Δ9-THC in utero were glucose intolerant, associated with blunted insulin response in muscle and increased serum insulin concentration 15 min after glucose challenge. Additionally, pancreata from male and female offspring were harvested at postnatal day 21 and 5 months of age for assessment of endocrine pancreas morphometry by immunostaining. This analysis revealed that gestational exposure to Δ9-THC reduced the density of islets in female, but not male, offspring at postnatal day 21 and 5 months, culminating in reduced β-cell mass at 5 months. These results demonstrate that fetal exposure to Δ9-THC causes female-specific impairments in glucose homeostasis, raising concern regarding the metabolic health of offspring, particularly females, exposed to cannabis in utero.

中文翻译：

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母体暴露于Δ9-四氢大麻酚会损害雌性子代葡萄糖稳态和大鼠内分泌胰腺发育。

最近的报告表明，北美有7％的怀孕母亲使用大麻。考虑到在子宫内暴露于Δ9-四氢大麻酚（Δ9-THC）中时，大麻中的主要精神活性成分会导致胎儿生长受限，并可能改变后代中胰腺β细胞的复制和存活，这令人担忧。因此，我们假设孕妇在怀孕期间暴露于Δ9-THC会损害后代的产后糖代谢健康。为了检验该假设，从妊娠第6天到出生，每天腹膜内注射3 mg / kgΔ9-THC或赋形剂治疗妊娠的Wistar大鼠。随后在5个月大时用葡萄糖和胰岛素攻击后代，以评估葡萄糖耐量和外周肌胰岛素敏感性。子宫内暴露于Δ9-THC的雌性后代对葡萄糖不耐受，与葡萄糖刺激后15分钟肌肉中胰岛素反应减弱和血清胰岛素浓度升高有关。另外，在出生后第21天和5个月大时收获雄性和雌性后代的胰腺，以通过免疫染色评估内分泌胰腺形态。该分析表明，孕期暴露于Δ9-THC会降低雌性而非雄性后代在出生后21天和5个月时胰岛的密度，最终在5个月时降低β细胞的质量。这些结果表明，胎儿暴露于Δ9-THC会导致女性体内葡萄糖体内稳态受损，从而引起人们对后代（尤其是女性）在子宫内接触大麻的代谢健康的担忧。另外，在出生后第21天和5个月大时收获雄性和雌性后代的胰腺，以通过免疫染色评估内分泌胰腺形态。该分析表明，孕期暴露于Δ9-THC会降低雌性而非雄性后代在出生后21天和5个月时胰岛的密度，最终在5个月时降低β细胞的质量。这些结果表明，胎儿暴露于Δ9-THC会引起女性葡萄糖稳态平衡的特定损伤，引起人们对后代（尤其是女性）在子宫内接触大麻的代谢健康的关注。另外，在出生后第21天和5个月大时收获雄性和雌性后代的胰腺，以通过免疫染色评估内分泌胰腺形态。该分析表明，孕期暴露于Δ9-THC会降低雌性而非雄性后代在出生后21天和5个月时胰岛的密度，最终在5个月时降低β细胞的质量。这些结果表明，胎儿暴露于Δ9-THC会引起女性葡萄糖稳态平衡的特定损伤，引起人们对后代（尤其是女性）在子宫内接触大麻的代谢健康的关注。该分析表明，孕期暴露于Δ9-THC会降低雌性而非雄性后代在出生后21天和5个月时胰岛的密度，最终在5个月时降低β细胞的质量。这些结果表明，胎儿暴露于Δ9-THC会导致女性体内葡萄糖体内稳态受损，从而引起人们对后代（尤其是女性）在子宫内接触大麻的代谢健康的担忧。该分析表明，妊娠后暴露于Δ9-THC会降低雌性而非雄性后代在出生后21天和5个月时胰岛的密度，最终在5个月时降低β细胞的质量。这些结果表明，胎儿暴露于Δ9-THC会引起女性葡萄糖稳态平衡的特定损伤，引起人们对后代（尤其是女性）在子宫内接触大麻的代谢健康的关注。