Department of Pediatrics and the Graduate Programme in Medical Sciences, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2022 Aug 17;17(8):e0272819. doi: 10.1371/journal.pone.0272819. eCollection 2022.
Pregnant and lactating women have been discouraged from using cannabis by Health Canada. However, the increasing rate of cannabis use among pregnant women has presented an urgent need to investigate its physiological effects during the perinatal period. During pregnancy, the mammary gland (MG) undergoes remodeling, which involves alveolar differentiation of mammary epithelial cells (MECs), which is essential for breast milk production and secretion. Limited evidence has been reported on the impact of cannabis or its components, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on MG development or MEC differentiation. In this study, we investigated the effects of THC and CBD on the differentiation of MECs by assessing changes in cellular viability, lipid accumulation, and gene and protein expression of major milk protein and lipid synthesizing markers. using the HC11 cells as a model. We hypothesized that THC and CBD will negatively impact the synthesis of milk proteins and lipids, as well as lipid markers in HC11 cells. Our results demonstrated that THC and CBD reduced cellular viability at concentrations above 30μM and 20μM, respectively. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP), lipid synthesizing and glucose transport markers (GLUT 1, HK2, FASN, FABP4, PLIN2 and LPL), as well as whey acidic protein and lipid levels. In addition, co-treatment of a CB2 antagonist with THC, and a CB2 agonist with CBD, reversed the impact of THC and CBD on the mRNA levels of key markers, respectively. In conclusion, 10μM THC and CBD altered the differentiation of HC11 cells, in part via the CB2 receptor.
加拿大卫生部曾劝阻孕妇和哺乳期妇女使用大麻。然而，孕妇中大麻使用量的不断增加，迫切需要研究大麻在围产期的生理作用。在妊娠期间，乳腺（MG）经历重塑，这涉及乳腺上皮细胞（MEC）的肺泡分化，这对于乳汁的产生和分泌至关重要。有有限的证据表明大麻或其成分（Δ-9-四氢大麻酚（THC）和大麻二酚（CBD））对MG 发育或 MEC 分化有影响。在这项研究中，我们通过评估主要乳蛋白和脂质合成标志物的细胞活力、脂质积累以及基因和蛋白表达的变化，研究了 THC 和 CBD 对 MEC 分化的影响，使用 HC11 细胞作为模型。我们假设 THC 和 CBD 将对 HC11 细胞中乳蛋白和脂质的合成以及脂质标志物产生负面影响。我们的结果表明，THC 和 CBD 在浓度高于 30μM 和 20μM 时分别降低细胞活力。与对照组相比，10μM THC 和 10μM CBD 降低了乳蛋白（CSN2 和 WAP）、脂质合成和葡萄糖转运标志物（GLUT1、HK2、FASN、FABP4、PLIN2 和 LPL）以及乳清酸性蛋白和脂质水平的 mRNA 水平。此外，用 CB2 拮抗剂与 THC 共同处理，以及用 CB2 激动剂与 CBD 共同处理，分别逆转了 THC 和 CBD 对关键标志物 mRNA 水平的影响。总之，10μM THC 和 CBD 通过 CB2 受体改变了 HC11 细胞的分化。
